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The African swine fever (ASF) epidemic has severely challenged the Philippines' swine industry since 2019. The National African Swine Fever Prevention and Control Program (NASFPCP), launched in 2021, aims to provide guidance for managing ASF through surveillance, monitoring, and swine repopulation. This study evaluates the effectiveness of post-outbreak disinfection protocols and government-mandated measures for repopulation standard. Surveillance data from three repopulation phases—(I) depopulation, cleaning, and disinfection; (II) downtime (20 days); and (III) sentinel animals (40 days)—were collected from February 2020 to December 2021 in the province of Batangas. Time-to-detection of positive events were analyzed for different farm types, seasons, or location using survival analysis modeling. Probability of detecting infected farms at different sampling times was estimated in terms of sensitivity of the sampling time. Data from 145 swine farms, including 99 backyard and 46 commercial farms, revealed positive rates of 10.1 and 8.7%, respectively. The failure rate during repopulation surveillance was 9.66%, whereas 90.34% farms remained ASF negative. Sensitivity estimate increased from 18–21 to 89% by day 27, with sentinel animals on that day exhibiting the highest estimated sensitivity. This highlights the importance of sentinel pigs in the NASFPCP for effective ASF control in the Philippines. Survival analysis showed no statistically significant differences in the results between either farm type, season, or municipality level. Geographic mapping of surveyed farms and those with positive detections identified high-risk locations including San Juan and Lipa City as key areas of concern. Enhancing targeted surveillance is critical for improving an early ASF detection and national response in the Philippines. [ABSTRACT FROM AUTHOR]

In recent years, great interest has been focused on the development of highly reproducible 3D in vitro models that are able to mimic the physiological architecture and functionality of native tissues. To date, a wide range of techniques have been proposed to recreate an intestinal barrier in vitro, including synthetic scaffolds and hydrogels, as well as complex on-a-chip systems and organoids. Here, we describe a novel protocol for the generation of an artificial intestine based on the creation of decellularized bio-scaffolds and their repopulation with intestinal stromal and epithelial cells. Organs collected at the local slaughterhouse are subjected to a decellularization protocol that includes a freezing/thawing step, followed by sequential incubation in 1% SDS for 12 h, 1% Triton X-100 for 12 h, and 2% deoxycholate for 12 h. At the end of the procedure, the generated bio-scaffolds are repopulated with intestinal fibroblasts and then with epithelial cells. The protocol described here represents a promising and novel strategy to generate an in vitro bioengineered intestine platform able to mimic some of the complex functions of the intestinal barrier, thus constituting a promising 3D strategy for nutritional, pharmaceutical, and toxicological studies. [ABSTRACT FROM AUTHOR]

Copyright of Croatian & Comparative Public Administration is the property of Institut za Javnu Upravu and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The African swine fever (ASF) epidemic has severely challenged the Philippines’ swine industry since 2019. The National African Swine Fever Prevention and Control Program (NASFPCP), launched in 2021, aims to provide guidance for managing ASF through surveillance, monitoring, and swine repopulation. This study evaluates the effectiveness of post-outbreak disinfection protocols and government-mandated measures for repopulation standard. Surveillance data from three repopulation phases—(I) depopulation, cleaning, and disinfection; (II) downtime (20 days); and (III) sentinel animals (40 days)—were collected from February 2020 to December 2021 in the province of Batangas. Time-to-detection of positive events were analyzed for different farm types, seasons, or location using survival analysis modeling. Probability of detecting infected farms at different sampling times was estimated in terms of sensitivity of the sampling time. Data from 145 swine farms, including 99 backyard and 46 commercial farms, revealed positive rates of 10.1 and 8.7%, respectively. The failure rate during repopulation surveillance was 9.66%, whereas 90.34% farms remained ASF negative. Sensitivity estimate increased from 18–21 to 89% by day 27, with sentinel animals on that day exhibiting the highest estimated sensitivity. This highlights the importance of sentinel pigs in the NASFPCP for effective ASF control in the Philippines. Survival analysis showed no statistically significant differences in the results between either farm type, season, or municipality level. Geographic mapping of surveyed farms and those with positive detections identified high-risk locations including San Juan and Lipa City as key areas of concern. Enhancing targeted surveillance is critical for improving an early ASF detection and national response in the Philippines.

Copyright of Historia Agraria is the property of Historia Agraria and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

In this work, a population viability analysis (PVA) is conducted on the population of Rhea pennata, a bird categorized as Critically Endangered (CR), with an estimated population size of 350 individuals in Peru. The data were analyzed using VORTEX 9.6 software, and eight scenarios and combinations were modeled to determine the annual population growth rate under the influence of anthropogenic, demographic, environmental, and genetic factors. The results indicate that the Rhea pennata population is not viable, with a negative population growth rate (r= -0.11), meaning the population decreases by 11% per year. A combined effect of anthropogenic factors, such as egg collection, genetic factors like inbreeding, and environmental factors such as intense snowfalls, further reduces the growth rate (r= -0.18). In this scenario, the probability of extinction occurs in approximately 50 years. The effect of inbreeding in an adult population of 50 individuals in a fragmented habitat would lead to extinction in approximately 25 to 30 years. The only scenario where the population is viable in the long term involves repopulation, requiring the release of 38 population groups over a period of 15 years in an area of approximately 27000 km², which must be under some conservation measure, such as protected natural areas or other area-based conservation measures. [ABSTRACT FROM AUTHOR]

Copyright of Hispania: Revista Española de Historia is the property of Consejo Superior de Investigaciones Cientificas and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Microglia are the brain's resident macrophages that play pivotal roles in immune surveillance and maintaining homeostasis of the Central Nervous System (CNS). Microglia are functionally implicated in various cerebrovascular diseases, including stroke, aneurysm, and tumorigenesis as they regulate neuroinflammatory responses and tissue repair processes. Here, we review the manifold functions of microglia in the brain under physiological and pathological conditions, primarily focusing on the implication of microglia in glioma propagation and progression. We further review the current status of therapies targeting microglial cells, including their re-education, depletion, and repopulation approaches as therapeutic options to improve patient outcomes for various neurological and neuroinflammatory disorders, including cancer. [ABSTRACT FROM AUTHOR]

Abstract Background Kupffer cells (KCs) originate from yolk-sac progenitors before birth. Throughout adulthood, they self-maintain independently from the input of circulating monocytes (MOs) at a steady state and are replenished within 2 weeks after having been depleted, but the origin of repopulating KCs in adults remains unclear. The current paradigm dictates that repopulating KCs originate from preexisting KCs or monocytes, but there remains a lack of fate-mapping evidence. Methods We first traced the fate of preexisting KCs and that of monocytic cells with tissue-resident macrophage-specific and monocytic cell-specific fate-mapping mouse models, respectively. Secondly, we performed genetic lineage tracing to determine the type of progenitor cells involved in response to KC-depletion in mice. Finally, we traced the fate of hematopoietic stem cells (HSCs) in an HSC-specific fate-mapping mouse model, in the context of chronic liver inflammation induced by repeated carbon tetrachloride treatment. Results By using fate-mapping mouse models, we found no evidence that repopulating KCs originate from preexisting KCs or MOs and found that in response to KC-depletion, HSCs proliferated in the bone marrow, mobilized into the blood, adoptively transferred into the liver and differentiated into KCs. Then, in the chronic liver inflammation context, we confirmed that repopulating KCs originated directly from HSCs. Conclusion Taken together, these findings provided in vivo fate-mapping evidence that repopulating KCs originate directly from HSCs, which presents a completely novel understanding of the cellular origin of repopulating KCs and shedding light on the divergent roles of KCs in liver homeostasis and diseases.

In recent years, great interest has been focused on the development of highly reproducible 3D in vitro models that are able to mimic the physiological architecture and functionality of native tissues. To date, a wide range of techniques have been proposed to recreate an intestinal barrier in vitro, including synthetic scaffolds and hydrogels, as well as complex on-a-chip systems and organoids. Here, we describe a novel protocol for the generation of an artificial intestine based on the creation of decellularized bio-scaffolds and their repopulation with intestinal stromal and epithelial cells. Organs collected at the local slaughterhouse are subjected to a decellularization protocol that includes a freezing/thawing step, followed by sequential incubation in 1% SDS for 12 h, 1% Triton X-100 for 12 h, and 2% deoxycholate for 12 h. At the end of the procedure, the generated bio-scaffolds are repopulated with intestinal fibroblasts and then with epithelial cells. The protocol described here represents a promising and novel strategy to generate an in vitro bioengineered intestine platform able to mimic some of the complex functions of the intestinal barrier, thus constituting a promising 3D strategy for nutritional, pharmaceutical, and toxicological studies.

Microglia are the brain’s resident macrophages that play pivotal roles in immune surveillance and maintaining homeostasis of the Central Nervous System (CNS). Microglia are functionally implicated in various cerebrovascular diseases, including stroke, aneurysm, and tumorigenesis as they regulate neuroinflammatory responses and tissue repair processes. Here, we review the manifold functions of microglia in the brain under physiological and pathological conditions, primarily focusing on the implication of microglia in glioma propagation and progression. We further review the current status of therapies targeting microglial cells, including their re-education, depletion, and re-population approaches as therapeutic options to improve patient outcomes for various neurological and neuroinflammatory disorders, including cancer.

In the 1980s, a significant number of Latin Americans began moving to urban centers in the Iberian peninsula. These arrivals grew exponentially. By 2022, Argentina, Bolivia, Brazil, Colombia, Cuba, Ecuador, Honduras, Paraguay, Peru, the Dominican Republic, and Venezuela each had more than 100,000 citizens in Spain. While cities have been the most visible poles of attraction for Latin American immigration, small towns have also witnessed the arrival of Latin Americans. Rural Spain, commonly known as "empty Spain," had been shrinking and waning in silence for decades, due to an aging population and the migration of young adults to the cities. In 2021 Spain's central government started to speak of migration as a solution for depopulation, but this proposal's origins date further back. In 2000 the local government of Aguaviva, a small town in Teruel, decided to bring back life to "empty Spain" by inviting Argentinian families to settle there in exchange for employment and housing. Since then, many more towns have followed suit. The documentary Aguaviva: La vida en tres maletas (2004, "Aguaviva: Life in Three Suitcases"), directed by Verónica Marchiaro and Mario Burbano, offers the story of this first rural repopulation. A close look at the diverse lived experiences portrayed in the documentary, and its different points of views on hospitality, can help guide current conversations on repopulation. [ABSTRACT FROM AUTHOR]

Reactivemicroglia are a hallmark of age-related retinal degenerative diseases including age-related macular degeneration (AMD). These cells are capable of secreting neurotoxic substances that may aggravate inflammation that leads to loss of photoreceptors and impaired vision. Despite their role in driving detrimental inflammation, microglia also play supporting roles in the retina as they are a crucial cellular component of the regulatory innate immune system. In this study, we used the colony stimulating factor 1 receptor (CSF1R)-antagonist PLX3397 to investigate the effects of microglia depletion and repopulation in a mouse model of acute retinal degeneration that mimics some aspects of dry AMD. Ourmain goal was to investigate whethermicroglia depletion and repopulation affects the outcome of light-induced retinal degeneration. We found that microglia depletion effectively decreased the expression of several key pro-inflammatory factors but was unable to influence the extent of retinal degeneration as determined by optical coherence tomography (OCT) and histology. Interestingly, we found prominent cell debris accumulation in the outer retina under conditions of microglia depletion, presumably due to the lack of efficient phagocytosis that could not be compensated by the retinal pigment epithelium. Moreover, our in vivo experiments showed that renewal of retinal microglia by repopulation did also not prevent rapid microglia activation or preserve photoreceptor death under conditions of light damage. We conclude that microglia ablation strongly reduces the expression of pro-inflammatory factors but cannot prevent photoreceptor loss in the light-damage paradigm of retinal degeneration. [ABSTRACT FROM AUTHOR]

Background: Kupffer cells (KCs) originate from yolk-sac progenitors before birth. Throughout adulthood, they self-maintain independently from the input of circulating monocytes (MOs) at a steady state and are replenished within 2 weeks after having been depleted, but the origin of repopulating KCs in adults remains unclear. The current paradigm dictates that repopulating KCs originate from preexisting KCs or monocytes, but there remains a lack of fate-mapping evidence. Methods: We first traced the fate of preexisting KCs and that of monocytic cells with tissue-resident macrophage-specific and monocytic cell-specific fate-mapping mouse models, respectively. Secondly, we performed genetic lineage tracing to determine the type of progenitor cells involved in response to KC-depletion in mice. Finally, we traced the fate of hematopoietic stem cells (HSCs) in an HSC-specific fate-mapping mouse model, in the context of chronic liver inflammation induced by repeated carbon tetrachloride treatment. Results: By using fate-mapping mouse models, we found no evidence that repopulating KCs originate from preexisting KCs or MOs and found that in response to KC-depletion, HSCs proliferated in the bone marrow, mobilized into the blood, adoptively transferred into the liver and differentiated into KCs. Then, in the chronic liver inflammation context, we confirmed that repopulating KCs originated directly from HSCs. Conclusion: Taken together, these findings provided in vivo fate-mapping evidence that repopulating KCs originate directly from HSCs, which presents a completely novel understanding of the cellular origin of repopulating KCs and shedding light on the divergent roles of KCs in liver homeostasis and diseases. [ABSTRACT FROM AUTHOR]

Microglia, the brain's resident myeloid cells, play central roles in brain defense, homeostasis, and disease. Using a prolonged colony-stimulating factor 1 receptor inhibitor (CSF1Ri) approach, we report an unprecedented level of microglial depletion and establish a model system that achieves an empty microglial niche in the adult brain. We identify a myeloid cell that migrates from the subventricular zone and associated white matter areas. Following CSF1Ri, these amoeboid cells migrate radially and tangentially in a dynamic wave filling the brain in a distinct pattern, to replace the microglial-depleted brain. These repopulating cells are enriched in disease-associated microglia genes and exhibit similar phenotypic and transcriptional profiles to white-matter-associated microglia. Our findings shed light on the overlapping and distinct functional complexity and diversity of myeloid cells of the CNS and provide new insight into repopulating microglia function and dynamics in the mouse brain.

Reactive microglia are a hallmark of age-related retinal degenerative diseases including age-related macular degeneration (AMD). These cells are capable of secreting neurotoxic substances that may aggravate inflammation that leads to loss of photoreceptors and impaired vision. Despite their role in driving detrimental inflammation, microglia also play supporting roles in the retina as they are a crucial cellular component of the regulatory innate immune system. In this study, we used the colony stimulating factor 1 receptor (CSF1R)-antagonist PLX3397 to investigate the effects of microglia depletion and repopulation in a mouse model of acute retinal degeneration that mimics some aspects of dry AMD. Our main goal was to investigate whether microglia depletion and repopulation affects the outcome of light-induced retinal degeneration. We found that microglia depletion effectively decreased the expression of several key pro-inflammatory factors but was unable to influence the extent of retinal degeneration as determined by optical coherence tomography (OCT) and histology. Interestingly, we found prominent cell debris accumulation in the outer retina under conditions of microglia depletion, presumably due to the lack of efficient phagocytosis that could not be compensated by the retinal pigment epithelium. Moreover, our in vivo experiments showed that renewal of retinal microglia by repopulation did also not prevent rapid microglia activation or preserve photoreceptor death under conditions of light damage. We conclude that microglia ablation strongly reduces the expression of pro-inflammatory factors but cannot prevent photoreceptor loss in the light-damage paradigm of retinal degeneration.

• Microglial repopulation attenuates AD-associated cognitive deficits. • Repopulating microglia enhance hippocampal LTP and synaptic proteins. • Repopulating microglia recover cell morphology and synaptic engulfment. • Microglial repopulation restores neurotrophic signaling and hippocampal neurogenesis. • Repopulation elevates BDNF expression from microglia, boosting synaptic plasticity. Over the past decade, compelling genetic evidence has highlighted the crucial role of microglial dysregulation in the development of Alzheimer's disease (AD). As resident immune cells in the brain, microglia undergo dystrophy and senescence during the chronic progression of AD. To explore the potential therapeutic benefits of replenishing the brain with new microglia in AD, we utilized the CSF1R inhibitor PLX3397 to deplete existing microglia and induce repopulation after inhibitor withdrawal in 5xFAD transgenic mice. Our findings revealed the remarkable benefits of microglial repopulation in ameliorating AD-associated cognitive deficits, accompanied by a notable elevation in synaptic proteins and an enhancement of hippocampal long-term potentiation (LTP). Additionally, we observed the profound restoration of microglial morphology and synaptic engulfment following their self-renewal. The impact of microglial repopulation on amyloid pathology is dependent on the duration of repopulation. Transcriptome analysis revealed a high resemblance between the gene expression profiles of repopulated microglia from 5xFAD mice and those of microglia from WT mice. Importantly, the dysregulated neurotrophic signaling pathway and hippocampal neurogenesis in the AD brain are restored following microglial replenishment. Lastly, we demonstrated that the repopulation restores the expression of brain-derived neurotrophic factor (BDNF) in microglia, thereby contributing to synaptic plasticity. In conclusion, our findings provide compelling evidence to support the notion that microglial self-renewal confers substantial benefits to the AD brain by restoring the BDNF neurotrophic signaling pathway. Thus, targeted microglial repopulation emerges as a highly promising and novel therapeutic strategy for alleviating cognitive impairment in AD. [ABSTRACT FROM AUTHOR]

Abstract Microglia, the resident phagocytes of the retina, are believed to influence the development of retinopathy, but their exact contributions to vascular integrity and neuronal loss are unknown. Therefore, utilizing two models of microglia depletion, we aimed to deplete and repopulate microglia to clarify the contribution of microglia to neuronal loss and vascular damage in the diabetic retina in an STZ-induced model of hyperglycemia. Here, we report that 2 weeks exposure to diphtheria toxin (DTx) in diabetic CX3CR1CreER:R26iDTR transgenic mice induced a 62% increase in Iba1+ microglia associated with an increase in TUJ1+ axonal density and prevention of NeuN+RBPMS+ neuronal loss. Conversely, diabetic PBS controls exhibited robust TUJ1+ axonal and NeuN+RBPMS+ neuronal loss compared to non-diabetic controls. A 2-week recovery period from DTx was associated with a 40% reduction in angiogenesis and an 85% reduction in fibrinogen deposition into the diabetic retina in comparison to diabetic PBS-treated controls. Analysis of microglia morphology and marker expression revealed that following a 2-week recovery period microglia displayed a P2RY12+Ly6C– phenotype and high transformation index (TI) values complimented by a ramified-surveillant morphology closely resembling non-diabetic controls. In contrast, diabetic PBS-treated control mice displayed P2RY12+Ly6C+ microglia, with a 50% reduction in TI values with an amoeboid morphology. To validate these observations were due to microglia depletion, we used PLX-5622 to assess vascular and neuronal damage in the retinas of diabetic mice. Confocal microscopy revealed that PLX-5622 also induced an increase in TUJ1+ axonal density and prevented fibrinogen extravasation into the diabetic retina. mRNAseq gene expression analysis in retinal isolates revealed that PLX-5622-induced microglia depletion and repopulation induced a downregulation in genes associated with microglial activation and phagocytosis, B2m, Cx3cr1, and Trem2, and complement-associated synaptic pruning, C1qa, C1qb, and C1qc. Although the levels of microglia depletion induced with DTx in the CX3CR1CreER:R26iDTR model and those induced with the CSF-1R antagonists are distinct, our results suggest that microglia depletion and replenishment is neuroprotective by inducing the proliferation of a homeostatic microglia pool that supports neuronal and vascular integrity.

Background: Prolonged exposure to general anesthetics during development is known to cause neurobehavioral abnormalities, but the cellular and molecular mechanisms involved are unclear. Microglia are the resident immune cells in the central nervous system and play essential roles in normal brain development. Materials and methods: In the study, postnatal day 7 (P7) C57BL/6 mice were randomly assigned to two groups. In the sevoflurane (SEVO), mice were exposed to 2.5% sevoflurane for 4 h. In the control group, mice were exposed to carrier gas (30% O2/70% N2) for 4 h. Fixed brain slices from P14 to P21 mice were immunolabeled for ionized calcium-binding adapter molecule 1 (IBA-1) to visualize microglia. The morphological analysis of microglia in the somatosensory cortex was performed using ImageJ and Imaris software. Serial block face scanning electron microscopy (SBF-SEM) was performed to assess the ultrastructure of the microglia and the contacts between microglia and synapse in P14 and P21 mice. The confocal imaging of brain slices was performed to assess microglia surveillance in resting and activated states in P14 and P21 mice. Behavioral tests were used to assess the effect of microglia depletion and repopulation on neurobehavioral abnormalities caused by sevoflurane exposure. Results: The prolonged exposure of neonatal mice to sevoflurane induced microglia hyper-ramification with an increase in total branch length, arborization area, and branch complexity 14  days after exposure. Prolonged neonatal sevoflurane exposure reduced contacts between microglia and synapses, without affecting the surveillance of microglia in the resting state or responding to laserinduced focal brain injury. These neonatal changes in microglia were associated with anxiety-like behaviors in adult mice. Furthermore, microglial depletion before sevoflurane exposure and subsequent repopulation in the neonatal brain mitigated anxiety-like behaviors caused by sevoflurane exposure. Conclusion: Our experiments indicate that general anesthetics may harm the developing brain, and microglia may be an essential target of general anestheticrelated developmental neurotoxicity. [ABSTRACT FROM AUTHOR]

This paper explores the contributions of neo-rural settlers to fire resilience in central Portugal, an area that has suffered from population decline and land abandonment for decades. An analysis of qualitative data from interviews with neo-rural settlers shows that they could be valuable partners in attempts to bolster several priorities of fire management in Portugal, including strengthening the property regime, creating a diversified rural landscape, and fostering collaborative networks in fire-affected areas. This article also presents some of the constraints that the settlers face in establishing themselves as agents of local landscape change and fire mitigation. • Neo-rural settlers are significant in abandoned areas of Portugal. • Fire prevention could benefit from working more directly with neo-rural settlers. • Neo-rural settlers can help recover a mosaic landscape with farming, grazing and forestry. • Settlers are buying and amending land use through formal and informal means. • Settlers create information networks on their land-based activities. [ABSTRACT FROM AUTHOR]

Microglia, the resident immune cell of the brain, can be eliminated via pharmacological inhibition of the colony-stimulating factor 1 receptor (CSF1R). Withdrawal of CSF1R inhibition then stimulates microglial repopulation, effectively replacing the microglial compartment. In the aged brain, microglia take on a "primed" phenotype and studies indicate that this coincides with age-related cognitive decline. Here, we investigated the effects of replacing the aged microglial compartment with new microglia using CSF1R inhibitor-induced microglial repopulation. With 28 days of repopulation, replacement of resident microglia in aged mice (24 months) improved spatial memory and restored physical microglial tissue characteristics (cell densities and morphologies) to those found in young adult animals (4 months). However, inflammation-related gene expression was not broadly altered with repopulation nor the response to immune challenges. Instead, microglial repopulation resulted in a reversal of age-related changes in neuronal gene expression, including expression of genes associated with actin cytoskeleton remodeling and synaptogenesis. Age-related changes in hippocampal neuronal complexity were reversed with both microglial elimination and repopulation, while microglial elimination increased both neurogenesis and dendritic spine densities. These changes were accompanied by a full rescue of age-induced deficits in long-term potentiation with microglial repopulation. Thus, several key aspects of the aged brain can be reversed by acute noninvasive replacement of microglia.

Copyright of Revista Iberoamericana de Educación (Version impresa) is the property of Organizacion de Estados Iberoamericanos (OEI) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Microglia, the resident phagocytes of the retina, are believed to influence the development of retinopathy, but their exact contributions to vascular integrity and neuronal loss are unknown. Therefore, utilizing two models of microglia depletion, we aimed to deplete and repopulate microglia to clarify the contribution of microglia to neuronal loss and vascular damage in the diabetic retina in an STZ-induced model of hyperglycemia. Here, we report that 2 weeks exposure to diphtheria toxin (DTx) in diabetic CX3CR1CreER:R26iDTR transgenic mice induced a 62% increase in Iba1+ microglia associated with an increase in TUJ1+ axonal density and prevention of NeuN+RBPMS+ neuronal loss. Conversely, diabetic PBS controls exhibited robust TUJ1+ axonal and NeuN+RBPMS+ neuronal loss compared to non-diabetic controls. A 2-week recovery period from DTx was associated with a 40% reduction in angiogenesis and an 85% reduction in fibrinogen deposition into the diabetic retina in comparison to diabetic PBS-treated controls. Analysis of microglia morphology and marker expression revealed that following a 2-week recovery period microglia displayed a P2RY12+Ly6C– phenotype and high transformation index (TI) values complimented by a ramified-surveillant morphology closely resembling non-diabetic controls. In contrast, diabetic PBS-treated control mice displayed P2RY12+Ly6C+ microglia, with a 50% reduction in TI values with an amoeboid morphology. To validate these observations were due to microglia depletion, we used PLX-5622 to assess vascular and neuronal damage in the retinas of diabetic mice. Confocal microscopy revealed that PLX-5622 also induced an increase in TUJ1+ axonal density and prevented fibrinogen extravasation into the diabetic retina. mRNAseq gene expression analysis in retinal isolates revealed that PLX-5622-induced microglia depletion and repopulation induced a downregulation in genes associated with microglial activation and phagocytosis, B2m, Cx3cr1, and Trem2, and complement-associated synaptic pruning, C1qa, C1qb, and C1qc. Although the levels of microglia depletion induced with DTx in the CX3CR1CreER:R26iDTR model and those induced with the CSF-1R antagonists are distinct, our results suggest that microglia depletion and replenishment is neuroprotective by inducing the proliferation of a homeostatic microglia pool that supports neuronal and vascular integrity. [ABSTRACT FROM AUTHOR]

The research is framed within the framework of studies on marginality which, in most of the Italian geographical literature, link the conceptual paradigm to much specific territorial dimensions (mountain areas, inland areas, rural areas).The different approaches, however, consider depopulation as a common condition of fragility, cause, and effect of expressions of spatial marginalization. With respect to this perspective, the demographic connotation of small municipalities is analyzed in terms of consistency, distribution and structure, in order to highlight the existence of a territorial pattern of dispersion, which is not geographically dichotomous, but widely spread and consistent throughout the country.Extreme forms of depopulation have also led to cases of abandonment, recognisable in the existence of numerous ’ghost towns’, fractions of territory that are now completely uninhabited; on the other hand, it has produced a constellation of ancient villages, in decay and at risk of abandonment, with respect to which, however, some repopulation hypotheses are beginning to be launched.Actions aimed at recovering and enhancing with the purpose of a new residentiality can be traced back to cases that escape an exhaustive recognition as well as to a superordinate, top-down planning, at a national level, but are entrusted to the action of local and regional actors even if the issue of repopulation of ancient villages is currently at the center of the National Recovery and Resilience Plan, testifying to the relevance of the theme.With respect to this scenario, revitalization hypotheses by local communities seem to be more effective, by regaining awareness of their own and non-reproducible territorial values and following an action in favour of a ’consciousness of place’ in relation to contemporaneity.

Marine forests is a term commonly used for coastal marine habitats formed by dense stands of brown macroalgae, typically consisting of kelp and fucoids. These habitats are highly productive, offer habitat to numerous marine organisms, and support a range of invaluable ecosystem services. Despite their importance, marine forests are declining in many regions around the world as a result of interacting global, regional, and local‐scale stressors. Consequently, interest in restoration as a tool to mitigate these declines and reinstate marine forests is growing.Recent reviews have provided insights into marine forest restoration; however, for the most part, a synthesis of restoration success is lacking. A meta‐analysis and quantitative review of published marine forest restoration efforts was conducted to examine: (i) how restoration affects the abundance and morphology of marine forest species; and (ii) trends in marine forest restoration success.The meta‐analysis of 25 studies revealed that restoration positively influences the abundance and morphology of marine forest species. The quantitative review of 63 studies demonstrated that taxa and restoration technique were important factors influencing restoration success, and revealed a bias towards the monitoring and reporting of abundance and morphological response variables. The review also highlighted a lack of monitoring and/or reporting of environmental variables at restoration sites, and limited comparative research across environmental contexts and restored species.It is shown that successful marine forest restoration is possible at experimental scales, but that better monitoring and reporting of restoration efforts, alongside increased project durations, could improve our understanding of restoration success at the ecosystem level. Considerations for future marine forest restoration efforts are also provided. It is hoped that the review will advance marine forest restoration efforts, allowing the preservation of these valuable ecosystems and their associated services. [ABSTRACT FROM AUTHOR]

Hatchery fish stocking is one of the main actions adopted as a form of conservation and replacement of fishing stocks. Under Brazilian law, the release of fish has become mandatory and is seen as one of the main ways of mitigating the negative effects on fish populations and preserving the ichthyofauna. Since its institution, the efficiency of this method has been questioned by the Brazilian scientific community, due to the lack of monitoring based on scientific criteria. The objective of this work was to discuss the few available reports and to analyze their deficiencies and analyze the real risks and/or benefits arising from the methodologies employed in hatchery stocking activities developed in Brazil. For this, three different studies developed in the Paranapanema River, Southeast/South of Brazil, were evaluated seeking evidence of the efficiency or inefficiency of these actions, such as management of the conservation of fish species and stocks. Our analysis shows that this management policy is poorly evaluated, and review of the planning of the stocking programs is essential, in order to improve, update, modernize, and unify the knowledge of the producing stations with respect to the existing ecological and genetic studies, aiming at better monitoring and greater effectiveness in the results advance. Also, a protocol is suggested to standardize and guide new conservationist policies of hatchery fish stocking. [ABSTRACT FROM AUTHOR]

Microglia are important resident immune cells in the central nervous system (CNS) and play an important role in its development, homeostasis, and disease treatments. Activated microglia perform diverse functions in mouse models of CNS neurodegenerative diseases or deficits. In humans, microglia have been linked to various neurodegenerative diseases. Following brain or spinal cord injury, microglia express pro- and anti-inflammatory phenotypes at different stages of recovery. With the development of pharmacological and genetic tools for microglial depletion, studies have demonstrated that microglial depletion exerts both positive and negative effects in the treatment of CNS diseases. Notably, microglial depletion provides an empty niche that stimulates production of new microglia. Microglial depletion and repopulation can not only treat diseases by eliminating dysfunctional microglia but can also provide an indication of the molecular mechanisms of diseases. Although this approach has shown impressive results, its use is still in its infancy. In this review, we summarize the current pharmacological and genetic tools for microglial depletion and highlight recent advances in microglial repopulation therapy for the treatment and functional recovery of neurological diseases and deficits. Finally, we briefly discuss the therapeutic challenges and prospective uses of microglial repopulation therapy. [ABSTRACT FROM AUTHOR]

Copyright of Intus-Legere Historia is the property of Intus-Legere Historia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Intus-Legere Historia is the property of Intus-Legere Historia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

In the central nervous system, immunologic surveillance and response are carried out, in large part, by microglia. These resident macrophages derive from myeloid precursors in the embryonic yolk sac, migrating to the brain and eventually populating local tissue prior to blood-brain barrier formation. Preserved for the duration of lifespan, microglia serve the host as more than just a central arm of innate immunity, also contributing significantly to the development and maintenance of neurons and neural networks, as well as neuroregeneration. The critical nature of these varied functions makes the characterization of key roles played by microglia in neurodegenerative disorders, especially Alzheimer’s disease, of paramount importance. While genetic models and rudimentary pharmacologic approaches for microglial manipulation have greatly improved our understanding of central nervous system health and disease, significant advances in the selective and near complete in vitro and in vivo depletion of microglia for neuroscience application continue to push the boundaries of research. Here we discuss the research efficacy and utility of various microglial depletion strategies, including the highly effective CSF1R inhibitor models, noteworthy insights into the relationship between microglia and neurodegeneration, and the potential for therapeutic repurposing of microglial depletion and repopulation.

While the specific mechanisms driving the migration and cell death of excess microglia resulting from clonal expansion are unclear, the phenomena suggest the tendency for microglia to reorganize and restore their homeostasis alongside clinical recovery. Colony-stimulating factor 1 receptor signaling is necessary for microglia viability, unmasking a microglia progenitor cell in the adult brain. Keywords: microglia; clonality; development; homeostasis; repopulation; neurodegeneration EN microglia clonality development homeostasis repopulation neurodegeneration 1 9 9 02/02/22 20220131 NES 220131 Introduction Microglia are brain-resident macrophages that carry out immune surveillance, support neurogenesis and neuronal survival, shape the neuronal network, and maintain tissue homeostasis (Nimmerjahn et al., [65]; Hanisch and Kettenmann, [42]; Sierra et al., [83]; Tremblay et al., [96]; Schafer et al., [79]; Ueno et al., [97]; Squarzoni et al., [86]; Schafer and Stevens, [80]; Diaz-Aparicio et al., [19]). It is currently unclear if microglia expressing "MGnD", "DAM", and similar non-homeostatic microglial phenotypes could be clonally related, or if clonally expanded microglia display transcriptomic heterogeneity in response to their microenvironment. Migration of microglia containing A from old I Cx3cr1 i SP +/- sp I 5xFAD i brain slice to healthy young wildtype brain tissue further argues for the active involvement of microglia in disease propagation (d'Errico et al., [18]). [Extracted from the article]

The well-established 3D organoid culture method enabled efficient expansion of cholangiocyte-like cells from intrahepatic (IHBD) and extrahepatic bile duct (EHBD) tissue biopsies. The extensive expansion capacity of these organoids enables various applications, from cholangiocyte disease modelling to bile duct tissue engineering. Recent research demonstrated the feasibility of culturing cholangiocyte organoids from bile, which was minimal-invasive collected via endoscopic retrograde pancreaticography (ERCP). However, a detailed analysis of these bile cholangiocyte organoids (BCOs) and the cellular region of origin was not yet demonstrated. In this study, we characterize BCOs and mirror them to the already established organoids initiated from IHBD- and EHBD-tissue. We demonstrate successful organoid-initiation from extrahepatic bile collected from gallbladder after resection and by ERCP or percutaneous transhepatic cholangiopathy from a variety of patients. BCOs initiated from these three sources of bile all show features similar to in vivo cholangiocytes. The regionalspecific characteristics of the BCOs are reflected by the exclusive expression of regional common bile duct genes (HOXB2 and HOXB3) by ERCP-derived BCOs and gallbladder-derived BCOs expressing gallbladder-specific genes. Moreover, BCOs have limited hepatocyte-fate differentiation potential compared to intrahepatic cholangiocyte organoids. These results indicate that organoid-initiating cells in bile are likely of local (extrahepatic) origin and are not of intrahepatic origin. Regarding the functionality of organoid initiating cells in bile, we demonstrate that BCOs efficiently repopulate decellularizedEHBDscaffolds and restore the monolayer of cholangiocyte-like cells in vitro. Bile samples obtained through minimally invasive procedures provide a safe and effective alternative source of cholangiocyte organoids. The shedding of (organoid-initiating) cholangiocytes in bile provides a convenient source of organoids for regenerative medicine. [ABSTRACT FROM AUTHOR]

Copyright of Anuario del Instituto de Historia Argentina is the property of Universidad Nacional de La Plata and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: The development of functional bioengineered small-diameter vascular grafts (SDVGs), represents a major challenge of tissue engineering. This study aimed to evaluate the repopulation efficacy of biological vessels, utilizing the cord blood platelet lysate (CBPL). Methods: Human umbilical arteries (hUAs, n = 10) were submitted to decellularization. Then, an evaluation of decellularized hUAs, involving histological, biochemical and biomechanical analysis, was performed. Wharton's Jelly (WJ) Mesenchymal Stromal Cells (MSCs) were isolated and characterized for their properties. Then, WJ-MSCs (1.5 x 106 cells) were seeded on decellularized hUAs (n = 5) and cultivated with (Group A) or without the presence of the CBPL, (Group B) for 30 days. Histological analysis involving immunohistochemistry (against Ki67, for determination of cell proliferation) and indirect immunofluorescence (against activated MAP kinase, additional marker for cell growth and proliferation) was performed. Results: The decellularized hUAs retained their initial vessel's properties, in terms of key-specific proteins, the biochemical and biomechanical characteristics were preserved. The evaluation of the repopulation process indicated a more uniform distribution of WJ-MSCs in group A compared to group B. The repopulated vascular grafts of group B were characterized by greater Ki67 and MAP kinase expression compared to group A. Conclusion: The results of this study indicated that the CBPL may improve the repopulation efficacy, thus bringing the biological SDVGs one step closer to clinical application. [ABSTRACT FROM AUTHOR]

Microglia, the brain’s resident myeloid cells, play central roles in brain defense, homeostasis, and disease. Using a prolonged colony-stimulating factor 1 receptor inhibitor (CSF1Ri) approach, we report an unprecedented level of microglial depletion and establish a model system that achieves an empty microglial niche in the adult brain. We identify a myeloid cell that migrates from the subventricular zone and associated white matter areas. Following CSF1Ri, these amoeboid cells migrate radially and tangentially in a dynamic wave filling the brain in a distinct pattern, to replace the microglial-depleted brain. These repopulating cells are enriched in disease-associated microglia genes and exhibit similar phenotypic and transcriptional profiles to white-matter-associated microglia. Our findings shed light on the overlapping and distinct functional complexity and diversity of myeloid cells of the CNS and provide new insight into repopulating microglia function and dynamics in the mouse brain.

Microglia are the brain’s resident immune cells with a tremendous capacity to autonomously self-renew. Because microglial self-renewal has largely been studied using static tools, its mechanisms and kinetics are not well understood. Using chronic in vivo two-photon imaging in awake mice, we confirm that cortical microglia show limited turnover and migration under basal conditions. Following depletion, however, microglial repopulation is remarkably rapid and is sustained by the dynamic division of remaining microglia, in a manner that is largely independent of signaling through the P2Y12 receptor. Mathematical modeling of microglial division demonstrates that the observed division rates can account for the rapid repopulation observed in vivo. Additionally, newly born microglia resemble mature microglia within days of repopulation, although morphological maturation is different in newly born microglia in P2Y12 knock out mice. Our work suggests that microglia rapidly locally and that newly born microglia do not recapitulate the slow maturation seen in development but instead take on mature roles in the CNS.

In this paper, I examine two alternative responses to the depopulation of marginal rural areas: 'repeopling' (repopulation) and 'rewilding' (often defined as ecosystem restoration via mammal reintroductions). Specifically, I aim to clarify large-scale land managers' perspectives on rewilding and repeopling, as well as how these perspectives relate to their land management practices. I focus my research on Scotland for three reasons: (1.) it is a country with significant marginal rural areas; (2.) it hosts many large-scale landowners; and (3.) 'rewilding' and 'repeopling' are present in the country's political discourse. To answer my research questions, I conducted structured interviews with eight large-scale land managers (representing conservation NGOs, community land trusts, and private estates) in a single marginal rural area in the Scottish Highlands. I conducted a thematic analysis of their perspectives on rewilding and repeopling, as well as their land management practices. In relation to perspectives, I found that 'rewilding' is a controversial term in the study site, and this controversy seems in part to relate to the term's diverse, often ambiguous, interpretations. Repeopling was more broadly supported, though with qualifications. In relation to land management practices, I found that conservation activities were dominant in the study site. From a political ecological perspective, the prominence of conservation activities even on lands managed by interviewees who opposed rewilding might be seen as an example of territorialisation by conservation actors. In contrast, one interviewee focused on renewable energy development which, by bridging conservation and repopulation concerns, could be interpreted as an instance of counterterritorialisation. • Highlights for "Rewilding and repeopling in Scotland: large-scale land managers' perspectives and practices". • 'Rewilding' is a controversial term in this study site. • 'Repeopling' is more broadly supported, though with qualifications. • Available funding steers land management towards conservation activities. • Renewable energy offers a controversial alternative to conservation activities. [ABSTRACT FROM AUTHOR]

Microglia are the resident immune cells of the central nervous system (CNS) and are increasingly recognized as critical players in development, brain homeostasis, and disease pathogenesis. The lifespan, maintenance, proliferation, and turnover of microglia are important factors that regulate microglial behavior and affect their roles in the CNS. However, emerging evidence suggests that microglia are morphologically and phenotypically distinct in different brain areas, at different ages, and during disease. Ongoing research focuses on understanding how microglia acquire specific phenotypes in response to extrinsic cues in the environment and how phenotypes are specified by intrinsic properties of different populations of microglia. With the development of pharmacological and genetic tools that allow the investigation of microglia in vivo, there have been considerable advances in understanding molecular signatures of both homeostatic microglia and those reacting to injury and disease. Here, we review the master gene regulators that define microglia as well as discuss the evidence that microglia are heterogeneous and fall into distinct clusters that display specific intrinsic properties and perform unique tasks in different settings. Taken together, the information presented supports the idea that microglia morphology and transcriptional heterogeneity should be considered when studying the complex nature of microglia and their roles in brain health and disease. [ABSTRACT FROM AUTHOR]

As an integral part of the innate immune system of the brain, resident microglia must react rapidly to the onset of brain injury and neurological disease. These dynamic cells then continue to shift their phenotype along a multidimensional continuum with overlapping pro- and anti-inflammatory states, allowing them to adapt to microenvironmental changes during the progression of brain disorders. However, the ability of microglia to shift phenotype through nimble molecular, structural, and functional changes comes at a cost, as the extreme pro-inflammatory states may prevent these professional phagocytes from clearing toxic debris and secreting tissue-repairing neurotrophic factors. Evolution has strongly favored heterogeneity in microglia in both the spatial and temporal dimensions—they can assume diverse roles in different brain regions, throughout the course of brain development and aging, and during the spatiotemporal progression of brain injuries and neurological diseases. Age and sex differences add further diversity to microglia functional status under physiological and pathological conditions. This article reviews recent advances in our knowledge of microglia with emphases on molecular mediators of phenotype shifts and functional diversity. We describe microglia-targeted therapeutic opportunities, including pharmacologic modulation of phenotype and repopulation of the brain with fresh microglia. With the advent of powerful new tools, research on microglia has recently accelerated in pace and may translate into potential therapeutics against brain injury and neurological disease. [ABSTRACT FROM AUTHOR]

Stroke is a leading cause of disability and mortality, with limited treatment options. After stroke injury, microglia and CNS‐resident macrophages are rapidly activated and regulate neuropathological processes to steer the course of functional recovery. To accelerate this recovery, microglia can engulf dying cells and clear irreparably‐damaged tissues, thereby creating a microenvironment that is more suitable for the formation of new neural circuitry. In addition, monocyte‐derived macrophages cross the compromised blood‐brain barrier to infiltrate the injured brain. The specific functions of myeloid lineage cells in brain injury and repair are diverse and dependent on phenotypic polarization statuses. However, it remains to be determined to what degree the CNS‐invading macrophages occupy different functional niches from CNS‐resident microglia. In this review, we describe the physiological characteristics and functions of microglia in the developing and adult brain. We also review (a) the activation and phenotypic polarization of microglia and macrophages after stroke, (b) molecular mechanisms that control polarization status, and (c) the contribution of microglia to brain pathology versus repair. Finally, we summarize current breakthroughs in therapeutic strategies that calibrate microglia/macrophage responses after stroke. The present review summarizes recent advances in microglial research in relation to stroke with emphases on microglial/macrophage phenotypic polarization and function in brain injury and repair. It also reviews the physiological characteristics and functions of microglia in the developing and adult brain, and describes current breakthroughs in therapeutic strategies that calibrate microglia/macrophage responses after stroke. [ABSTRACT FROM AUTHOR]

Purpose: To analyze the multimodal imaging features in a case showing resolution of retinal pigment epithelium (RPE) apertures in association with an avascular pigment epithelium detachment secondary to nonneovascular age-related macular degeneration. Methods: Report of a case diagnosed with aperture of the RPE with multimodal imaging long-term follow-up. Color fundus photography, fundus autofluorescence, eye-tracked spectral domain optical coherence tomography (OCT), and OCT angiography findings are discussed. Results: A 71-year-old man diagnosed with nonneovascular age-related macular degeneration presented with three different areas of RPE aperture in his right eye. At baseline, best-corrected visual acuity was 20/100 in his right eye. Dilated fundus examination showed three round areas of RPE atrophy, and fundus autofluorescence demonstrated marked hypoautofluorescence in the corresponding areas. The OCT scans showed discontinuities of the RPE band with no evidence of RPE tear. The OCT angiography showed no evidence of abnormal blood flow within the sub-RPE space. Over time, fundus autofluorescence and eye-tracked spectral domain OCT scans demonstrated spontaneous resolution of two of the RPE defects and reduction of the size of the third one, with complete flattening of the pigment epithelium detachment. Conclusion: Distinction between RPE tears and apertures is important due to their different etiopathogenic mechanism and prognosis. To the best of our knowledge, this is the first report of a case of complete closure of an RPE aperture. The mechanism of the observed RPE closure remains unknown, and further studies are warranted to better understand the mechanisms of RPE restoration and remodeling. [ABSTRACT FROM AUTHOR]

Background: In spite of advances in the treatment of cartilage defects using cell and scaffold-based therapeutic strategies, the long-term outcome is still not satisfying since clinical scores decline years after treatment. Scaffold materials currently used in clinical settings have shown limitations in providing suitable biomechanical properties and an authentic and protective environment for regenerative cells. To tackle this problem, we developed a scaffold material based on decellularised human articular cartilage. Methods: Human articular cartilage matrix was engraved using a CO2 laser and treated for decellularisation and glycosaminoglycan removal. Characterisation of the resulting scaffold was performed via mechanical testing, DNA and GAG quantification and in vitro cultivation with adipose-derived stromal cells (ASC). Cell vitality, adhesion and chondrogenic differentiation were assessed. An ectopic, unloaded mouse model was used for the assessment of the in vivo performance of the scaffold in combination with ASC and human as well as bovine chondrocytes. The novel scaffold was compared to a commercial collagen type I/III scaffold. Findings: Crossed line engravings of the matrix allowed for a most regular and ubiquitous distribution of cells and chemical as well as enzymatic matrix treatment was performed to increase cell adhesion. The biomechanical characteristics of this novel scaffold that we term CartiScaff were found to be superior to those of commercially available materials. Neo-tissue was integrated excellently into the scaffold matrix and new collagen fibres were guided by the laser incisions towards a vertical alignment, a typical feature of native cartilage important for nutrition and biomechanics. In an ectopic, unloaded in vivo model, chondrocytes and mesenchymal stromal cells differentiated within the incisions despite the lack of growth factors and load, indicating a strong chondrogenic microenvironment within the scaffold incisions. Cells, most noticeably bone marrow-derived cells, were able to repopulate the empty chondrocyte lacunae inside the scaffold matrix. Interpretation: Due to the better load-bearing, its chondrogenic effect and the ability to guide matrix-deposition, CartiScaff is a promising biomaterial to accelerate rehabilitation and to improve long term clinical success of cartilage defect treatment. Funding: Austrian Research Promotion Agency FFG (“CartiScaff” #842455), Lorenz Böhler Fonds (16/13), City of Vienna Competence Team Project Signaltissue (MA23, #18-08)