Multiple Facets of Cellular Homeostasis and Regeneration of the Mammalian Liver.

Liver regeneration occurs in response to diverse injuries and is capable of functionally reestablishing the lost parenchyma. This phenomenon has been known since antiquity, encapsulated in the Greek myth where Prometheus was to be punished by Zeus for sharing the gift of fire with humanity by having an eagle eat his liver daily, only to have the liver regrow back, thus ensuring eternal suffering and punishment. Today, this process is actively leveraged clinically during living donor liver transplantation whereby up to a two-thirds hepatectomy (resection or removal of part of the liver) on a donor is used for transplant to a recipient. The donor liver rapidly regenerates to recover the lost parenchymal mass to form a functional tissue. This astonishing regenerative process and unique capacity of the liver are examined in further detail in this review.

A ZNRF3-dependent Wnt/ß-catenin signaling gradient is required for adrenal homeostasis.

Spatiotemporal control of Wnt signaling is essential for the development and homeostasis of many tissues. The transmembrane E3 ubiquitin ligases ZNRF3 (zinc and ring finger 3) and RNF43 (ring finger protein 43) antagonize Wnt signaling by promoting degradation of frizzled receptors. ZNRF3 and RNF43 are frequently inactivated in human cancer, but the molecular and therapeutic implications remain unclear. Here, we demonstrate that adrenocortical-specific loss of ZNRF3, but not RNF43, results in adrenal hyperplasia that depends on Porcupine-mediated Wnt ligand secretion. Furthermore, we discovered a Wnt/ß-catenin signaling gradient in the adrenal cortex that is disrupted upon loss of ZNRF3. Unlike ß-catenin gain-of-function models, which induce high Wnt/ß-catenin activation and expansion of the peripheral cortex, ZNRF3 loss triggers activation of moderate-level Wnt/ß-catenin signaling that drives proliferative expansion of only the histologically and functionally distinct inner cortex. Genetically reducing ß-catenin dosage significantly reverses the ZNRF3-deficient phenotype. Thus, homeostatic maintenance of the adrenal cortex is dependent on varying levels of Wnt/ß-catenin activation, which is regulated by ZNRF3.

Genetic dissection of intercellular interactions in vivo by membrane-permeable protein.

Unraveling cell-cell interaction is fundamental to understanding many biological processes. To date, genetic tools for labeling neighboring cells in mammals are not available. Here, we developed a labeling strategy based on the Cre-induced intercellular labeling protein (CILP). Cre-expressing donor cells release a lipid-soluble and membrane-permeable fluorescent protein that is then taken up by recipient cells, enabling fluorescent labeling of neighboring cells. Using CILP, we specifically labeled endothelial cells surrounding a special population of hepatocytes in adult mice and revealed their distinct gene signatures. Our results highlight the potential of CILP as a platform to reveal cell-cell interactions and communications in vivo.

Spatial transcriptomics unravels palmitoylation and zonation-dependent gene regulation by AEG-1 in mouse liver.

Obesity-induced metabolic dysfunction-associated steatohepatitis (MASH) leads to hepatocellular carcinoma (HCC). Astrocyte-elevated gene-1/Metadherin (AEG-1/MTDH) plays a key role in promoting MASH and HCC. AEG-1 is palmitoylated at residue cysteine 75 (Cys75) and a knock-in mouse representing mutated Cys75 to serine (AEG-1-C75S) showed activation of MASH- and HCC-promoting gene signature when compared to wild-type littermates (AEG-1-WT). The liver consists of three zones, periportal, mid-lobular, and pericentral, and zone-specific dysregulated gene expression impairs metabolic homeostasis in the liver, contributing to MASH and HCC. Here, to elucidate how palmitoylation influences AEG-1-mediated gene regulation in regard to hepatic zonation, we performed spatial transcriptomics (ST) in the livers of AEG-1-WT and AEG-1-C75S littermates. ST identified six different clusters in livers and using zone- and cell-type-specific markers we attributed specific zones and cell types to specific clusters. Ingenuity Pathway Analysis (IPA) of differentially expressed genes in each cluster unraveled activation of pro-inflammatory and MASH- and HCC-promoting pathways, mainly in periportal and pericentral hepatocytes, in AEG-1-C75S liver compared to AEG-1-WT. Interestingly, in AEG-1-C75S liver, the mid-lobular zone exhibited widespread inhibition of xenobiotic metabolism pathways and inhibition of PXR/RXR and LXR/RXR activation, versus AEG-1-WT. In conclusion, AEG-1-C75S mutant exhibited zone-specific differential gene expression, which might contribute to metabolic dysfunction and dysregulated drug metabolism leading to MASH and HCC.

Spatial lipidomics reveals zone-specific hepatic lipid alteration and remodeling in metabolic dysfunction-associated steatohepatitis.

Alteration in lipid metabolism plays a pivotal role in developing metabolic dysfunction-associated steatohepatitis (MASH). However, our understanding of alteration in lipid metabolism across liver zonation in MASH remains limited. Within this study, we investigated MASH-associated zone-specific lipid metabolism in a diet and chemical-induced MASH mouse model. Spatial lipidomics using mass spectrometry imaging in a MASH mouse model revealed 130 lipids from various classes altered across liver zonation and exhibited zone-specific lipid signatures in MASH. Triacylglycerols, diacylglycerols, sphingolipids and ceramides showed distinct zone-specific changes and re-distribution from pericentral to periportal localization in MASH. Saturated and monounsaturated fatty acids (FA) were the primary FA composition of increased lipids in MASH, while polyunsaturated FAs were the major FA composition of decreased lipids. We observed elevated fibrosis in the periportal region, which could be the result of observed metabolic alteration across zonation. Our study provides valuable insights into zone-specific hepatic lipid metabolism and demonstrates the significance of spatial lipidomics in understanding liver lipid metabolism. Identifying unique lipid distribution patterns may offer valuable insights into the pathophysiology of MASH and facilitate the discovery of diagnostic markers associated with liver zonation.

Role of endothelial PDGFB in arterio-venous malformations pathogenesis.

Arterial-venous malformations (AVMs) are direct connections between arteries and veins without an intervening capillary bed. Either familial inherited or sporadically occurring, localized pericytes (PCs) drop is among the AVMs' hallmarks. Whether impaired PC coverage triggers AVMs or it is a secondary event is unclear. Here we evaluated the role of the master regulator of PC recruitment, Platelet derived growth factor B (PDGFB) in AVM pathogenesis. Using tamoxifen-inducible deletion of Pdgfb in endothelial cells (ECs), we show that disruption of EC Pdgfb-mediated PC recruitment and maintenance leads to capillary enlargement and organotypic AVM-like structures. These vascular lesions contain non-proliferative hyperplastic, hypertrophic and miss-oriented capillary ECs with an altered capillary EC fate identity. Mechanistically, we propose that PDGFB maintains capillary EC size and caliber to limit hemodynamic changes, thus restricting expression of Krüppel like factor 4 and activation of Bone morphogenic protein, Transforming growth factor ß and NOTCH signaling in ECs. Furthermore, our study emphasizes that inducing or activating PDGFB signaling may be a viable therapeutic approach for treating vascular malformations.

MitoTracker Red for isolation of zone-specific hepatocytes and characterization of hepatic sublobular metabolism.

BACKGROUND: The liver lobule is divided into three zones or regions: periportal (PP or Zone 1) that is highly oxidative and active in ureagenesis, pericentral (PC or Zone 3) that is more glycolytic, and midzonal (MZ or Zone 2) with intermediate characteristics. AIM: Our goal was to isolate and metabolically characterize hepatocytes from specific sublobular zones. METHODS: Mice were administered rhodamine123 (Rh123) or MitoTracker Red (MTR) prior to intravital imaging, liver fixation, or hepatocyte isolation. After in vivo MTR, hepatocytes were isolated and sorted based on MTR fluorescence intensity. Alternatively, E-cadherin (Ecad) and cytochrome P450 2E1 (CYP2E1) immunolabeling was performed in fixed liver slices. Ecad and CYP2E1 gene expression in sorted hepatocytes was assessed by qPCR. Oxygen consumption rates (OCR) of sorted hepatocytes were also assessed. RESULTS: Multiphoton microscopy showed Rh123 and MTR fluorescence distributed zonally, decreasing from PP to PC in a flow-dependent fashion. In liver cross-sections, Ecad was expressed periportally and CYP2E1 pericentrally in association with high and low MTR labeling, respectively. Based on MTR fluorescence, hepatocytes were sorted into PP, MZ, and PC populations with PP and PC hepatocytes enriched in Ecad and CYP2E1, respectively. OCR of PP hepatocytes was ∼4 times that of PC hepatocytes. CONCLUSIONS: MTR treatment in vivo delineates sublobular hepatic zones and can be used to sort hepatocytes zonally. PP hepatocytes have substantially greater OCR compared to PC and MZ. The results also indicate a sharp midzonal demarcation between hepatocytes with PP characteristics (Ecad) and those with PC features (CYP2E1). This new method to sort hepatocytes in a zone-specific fashion holds the potential to shed light on sublobular hepatocyte metabolism and regulatory pathways in health and disease.

Zonated iron deposition in the periportal zone of the liver is associated with selectively enhanced lipid synthesis.

BACKGROUND AND AIMS: Disorders in liver lipid metabolism have been implicated in a range of metabolic conditions, including fatty liver and liver cancer. Altered lipid distribution within the liver, shifting from the pericentral to the periportal zone under pathological circumstances, has been observed; however, the underlying mechanism remains elusive. Iron, an essential metal, exhibits a zonal distribution in the liver similar to that of lipids. Nevertheless, the precise relationship between iron and lipid distribution, especially in the pericentral and periportal zones, remains poorly understood. METHODS: We conducted comprehensive in vitro and in vivo experiments, combining with in situ analysis and RNA sequencing, aiming for a detailed exploration of the causal relationship between iron accumulation and lipid metabolism. RESULTS: Our research suggests that iron overload can disrupt the normal distribution of lipids within the liver, particularly in the periportal zone. Through meticulous gene expression profiling in both the pericentral and periportal zones, we identified pyruvate carboxylase (PC) as a pivotal regulator in iron overload-induced lipid accumulation. Additionally, we revealed that the activation of cyclic adenosine monophosphate response element binding protein (CREB) was indispensable for Pc gene expression when in response to iron overload. CONCLUSIONS: In summary, our investigation unveils the crucial involvement of iron overload in fostering hepatic lipid accumulation in the periportal zone, at least partly mediated by the modulation of Pc expression. These insights offer new perspectives for understanding the pathogenesis of fatty liver diseases and their progression.

Spatial prioritization for widespread invasive species control: Trade-offs between current impact and future spread.

Spatially explicit prioritization of invasive species control is a complex issue, requiring consideration of trade-offs between immediate and future benefits. This study aimed to prioritize management efforts to account for current and future threats from widespread invasions and examine the strength of the trade-off between these different management goals. As a case study, we identified spatially explicit management priorities for the widespread invasion of introduced willow into riparian and wetland habitats across a 102,145-km2 region in eastern Australia. In addition to targeting places where willow threatens biodiversity now, a second set of management goals was to limit reinfestation and further spread that could occur via two different mechanisms (downstream and by wind). A model of likely willow distribution across the region was combined with spatial data for biodiversity (native vegetation, threatened species and communities), ecological conditions, management costs, and two potential dispersal layers. We used systematic conservation planning software (Zonation) to prioritize where willow management should be focussed across more than 100,000 catchments for a range of different scenarios that reflected different weights between management goals. For willow invasion, we found that we could prioritize willow management to reduce the future threat of dispersal downstream with little reduction in the protection of biodiversity. However, accounting for future threats from wind dispersal resulted in a stronger trade-off with protection of threatened biodiversity. The strongest trade-off was observed when both dispersal mechanisms were considered together. This study shows that considering current and future goals together offers the potential to substantially improve conservation outcomes for invasive species management. Our approach also informs land managers about the relative trade-offs among different management goals under different control scenarios, helping to make management decisions more transparent. This approach can be used for other widespread invasive species to help improve invasive species management decisions.

Zonation of bulk and rhizosphere soil bacterial communities and their covariation patterns along the elevation gradient in riparian zones of three Gorges reservoir, China.

Zonation is a typical pattern of soil distribution and species assembly across riparian habitats. Microorganisms are essential members of riparian ecosystems and whether soil microbial communities demonstrate similar zonation patterns and how bulk and rhizosphere soil microorganisms interact along the elevation (submergence stress) gradient remain largely unknown. In this study, bulk and rhizosphere (dominant plant) soil samples were collected and investigated across riparian zones where the submergence stress intensity increased as the elevation decreased. Results showed that the richness of bacterial communities in bulk and rhizosphere soil samples was significantly different and presented a zonation pattern along with the submergence stress gradient. Bulk soil at medium elevation that underwent moderate submergence stress had the most abundant bacterial communities, while the species richness of rhizobacteria at low elevation that experienced serious submergence stress was the highest. Additionally, principal coordinate analysis (PCoA) and significance tests showed that bulk and rhizosphere soil samples were distinguished according to the structure of bacterial communities, and so were bulk or rhizosphere soil samples from different elevations. Redundancy analysis (RDA) and Mantel test suggested that bacterial communities of bulk soil mainly relied on the contents of soil organic matter, total carbon (TC), total nitrogen (TN), sodium (Na), calcium (Ca) and magnesium (Mg). Contrastingly, the contents of Na and Mg were the main factors explaining the variation in rhizobacterial community composition. Correlation and microbial source tracking analyses showed thatthe relationship of bulk and rhizosphere soil bacteria became much stronger, and the rhizosphere soil may get more bacterial communities from bulk soil with the increase in submergence severity. Our results suggest that the abiotic and biotic components of the riparian ecosystem are closely covariant along the submergence stress gradient and imply that the bacterial community may be a key node linking soil physiochemical properties and vegetation communities.

Acetaminophen overdose causes a breach of the blood-bile barrier in mice but not in rats.

Acetaminophen (APAP) is known to cause a breach of the blood-bile barrier in mice that, via a mechanism called futile bile acid (BA) cycling, increases BA concentrations in hepatocytes above cytotoxic thresholds. Here, we compared this mechanism in mice and rats, because both species differ massively in their susceptibility to APAP and compared the results to available human data. Dose and time-dependent APAP experiments were performed in male C57BL6/N mice and Wistar rats. The time course of BA concentrations in liver tissue and in blood was analyzed by MALDI-MSI and LC-MS/MS. APAP and its derivatives were measured in the blood by LC-MS. APAP-induced liver damage was analyzed by histopathology, immunohistochemistry, and by clinical chemistry. In mice, a transient increase of BA in blood and in peri-central hepatocytes preceded hepatocyte death. The BA increase coincided with oxidative stress in liver tissue and a compromised morphology of bile canaliculi and immunohistochemically visualized tight junction proteins. Rats showed a reduced metabolic activation of APAP compared to mice. However, even at very high doses that caused cell death of hepatocytes, no increase of BA concentrations was observed neither in liver tissue nor in the blood. Correspondingly, no oxidative stress was detectable, and the morphology of bile canaliculi and tight junction proteins remained unaltered. In conclusion, different mechanisms cause cell death in rats and mice, whereby oxidative stress and a breach of the blood-bile barrier are seen only in mice. Since transient cholestasis also occurs in human patients with APAP overdose, mice are a clinically relevant species to study APAP hepatotoxicity but not rats.

Current status of coral disease prevalence at Karimunjawa Island: correlation between land zonation and lesion occurrence.

Coral diseases have contributed significantly to the decline of coral populations at both local and global scales. The Karimunjawa Archipelago, located off the coast of Java in Indonesia, is a marine national park with a zonation-based approach, designated by the local government due to its rich coral reef biodiversity. Unfortunately, there is a limited amount of research regarding the prevalence of coral diseases in coral reefs located on the islands. We analyzed the coral reef lesion assemblages at 6 sites within 3 designated zones, namely Tourism, Aquaculture, and Core zones. Our investigation aimed to determine (1) the types, prevalence, and patterns of coral lesions, (2) the correlation between coral cover and lesion prevalence, and (3) the susceptibility of coral taxa to lesions. A significant difference of 80.54% in the total number of coral lesions was observed between the tourism zone (24.34%) and the core zone (10.36%). Fourteen different lesion types were identified; among the non-disease lesions, sediment damage was the most prevalent (9.95%), followed by disease lesions caused by white syndrome (3.7%). A correlation was found between the cover of dominant coral taxa and the prevalence of lesions (disease and non-disease) at all sites. Mean lesion prevalence across all zones ranged from moderate to high categories. These findings present current data on the distribution of coral lesions and their patterns across zones around Karimunjawa Island. Research on the etiology and epidemiology of coral lesions should be promoted to identify ways to prevent the spread of coral diseases in Karimunjawa.

The interior climate and its microclimatic variation of temperate forests in Northern Patagonia, Argentina.

Knowledge on mesoclimatic zonation and microclimatic variations within mountain forest ecosystems is crucial for understanding regional species turnover and effects of climate change on these systems. The temperate mountain forests in the Andean region of South America are among the largest and contiguous natural deciduous forest areas in the world. Due to their pronounced disturbance regime and different successional stages, a climatic zonation combined with the characterisation of its microclimatic variation is important to identify thresholds of species occurrences.We used micro-loggers to measure air temperature and relative humidity for one year at 40 measurement locations along longitudinal and elevation gradients in mountain forests in Northern Patagonia, Argentina. Our results unveil mesoclimatic patterns within these forests characterised by variations in temperature and vapour pressure deficit along the elevational gradient in general, but also at different times of the year. For example, Austrocedrus chilensis and Nothofagus dombeyi forests differed mainly by temperature and its diurnal range in the warmest months of the year. Also, differences between forest stands and gaps were more pronounced in the warmest months of the year and at lower elevations, with up to 2.5 K higher temperatures in the second half of the day in gaps. We found clear indications that shrubland of Nothofagus antarctica representing a successional stage after disturbances alters the mesoclimatic pattern, favouring forest fire ignition. Such mesoclimatic variations have a major influence on tree species turnover and ecological processes within these forest ecosystems.The findings contribute to our understanding of the complex interplay between topography, climate, and vegetation in shaping the spatial patterns of species occurrences.

The adrenal capsule is a signaling center controlling cell renewal and zonation through Rspo3.

Adrenal glands are zonated endocrine organs that are essential in controlling body homeostasis. How zonation is induced and maintained and how renewal of the adrenal cortex is ensured remain a mystery. Here we show that capsular RSPO3 signals to the underlying steroidogenic compartment to induce ß-catenin signaling and imprint glomerulosa cell fate. Deletion of RSPO3 leads to loss of SHH signaling and impaired organ growth. Importantly, Rspo3 function remains essential in adult life to ensure replenishment of lost cells and maintain the properties of the zona glomerulosa. Thus, the adrenal capsule acts as a central signaling center that ensures replacement of damaged cells and is required to maintain zonation throughout life.

Multi-objective ecological restoration priority in China: Cost-benefit optimization in different ecological performance regimes based on planetary boundaries.

In the context of the "United Nations Decade on Ecosystem Restoration", optimizing spatiotemporal arrangements for ecological restoration is an important approach to enhancing overall socioecological benefits for sustainable development. However, against the background of ecological degradation caused by the human use of most natural resources at levels that have approached or exceeded the safe and sustainable boundaries of ecosystems, it is key to explain how to optimize ecological restoration by classified management and optimal total benefits. In response to these issues, we combined spatial heterogeneity and temporal dynamics at the national scale in China to construct five ecological performance regimes defined by indicators that use planetary boundaries and ecological pressures which served as the basis for prioritizing ecological restoration areas and implementing zoning control. By integrating habitat conservation, biodiversity, water supply, and restoration cost constraints, seven ecological restoration scenarios were simulated to optimize the spatial layout of ecological restoration projects (ERPs). The results indicated that the provinces with unsustainable freshwater use, climate change, and land use accounted for more than 25%, 66.7%, and 25%, respectively, of the total area. Only 30% of the provinces experienced a decrease in environmental pressure. Based on the ecological performance regimes, ERP sites spanning the past 20 years were identified, and more than 50% of the priority areas were clustered in regime areas with increased ecological stress. As the restoration area targets doubled (40%) from the baseline (20%), a multi-objective scenario presents a trade-off between expanded ERPs in areas with highly beneficial effects and minimal restoration costs. In conclusion, a reasonable classification and management regime is the basis for targeted restoration. Coordinating multiple objectives and costs in ecological restoration is the key to maximizing socio-ecological benefits. Our study offered new perspectives on systematic and sustainable planning for ecological restoration.

Strategic restoration planning for land birds in the Colorado River Delta, Mexico.

Ecological restoration is an essential strategy for mitigating the current biodiversity crisis, yet restoration actions are costly. We used systematic conservation planning principles to design an approach that prioritizes restoration sites for birds and tested it in a riparian forest restoration program in the Colorado River Delta. Restoration goals were to maximize the abundance and diversity of 15 priority birds with a variety of habitat preferences. We built abundance models for priority birds based on the current landscape, and predicted bird distributions and relative abundances under a scenario of complete riparian forest restoration throughout our study area. Then, we used Zonation conservation planning software to rank this restored landscape based on core areas for all priority birds. The locations with the highest ranks represented the highest priorities for restoration and were located throughout the river reach. We optimized how much of the available landscape to restore by simulating restoration of the top 10-90% of ranked sites in 10% intervals. We found that total diversity was maximized when 40% of the landscape was restored, and mean relative abundance was maximized when 80% of the landscape was restored. The results suggest that complete restoration is not optimal for this community of priority birds and restoration of approximately 60% of the landscape would provide a balance between maximum relative abundance and diversity. Subsequent planning efforts will combine our results with an assessment of restoration costs to provide further decision support for the restoration-siting process. Our approach can be applied to any landscape-scale restoration program to improve the return on investment of limited economic resources for restoration.

In-reservoir transformation of dissolved organic matter as a function of hydrological flow.

Reservoirs are vital to meet the ever-increasing demands for freshwater in a warming climate. Dissolved organic matter (DOM) represents an important pool of carbon and can be a major concern in drinking water sources. However, insights into DOM dynamics in temperate, semi-arid reservoirs remain limited. Therefore, we investigated the variations in DOM properties in Lake Diefenbaker, a large reservoir on the Canadian Prairies, by analyzing eight years of DOM concentrations and composition through linear mixed effect modeling. Contrary to expectations, reservoir dissolved organic carbon (DOC) concentration showed no correlation with inflow from the South Saskatchewan River (p = 0.12), while dissolved organic nitrogen (DON) increased with decreasing inflow (p = 0.002). DOM optical indices (SUVA254 and E4:E6 ratio) and DOC:DON ratio revealed a pronounced influence of inflow on reservoir DOM composition (p < 0.001), i.e., allochthonous characteristics increased with increasing flow, and autochthonous characteristics increased with declining flow. Travel time corrected comparison of approximately the same water parcel along the reservoir length revealed that increasing water residence time in downstream regions led to a significant transformation in DOM composition, favoring autochthonous characteristics (mean SUVA254 reduced by 0.52 L mg-C-1 m-1, and the E4:E6 and spectral slope ratio increased by 1.6 and 0.06, respectively). Autochthonous DOC inputs likely offset the allochthonous DOC losses, which resulted in a relatively stable DOC concentration throughout the reservoir (mean 3.7 mg L-1). Additionally, the effect of a large aquaculture operation on reservoir DOM properties was investigated, but no effect was detected. The results have significant implications for managing large river-reservoirs. Autochthonous DOM poses challenges to water processing, necessitating monitoring of DOM composition for reservoir drinking water quality. Insights on climate-induced changes in DOM properties will also assist with understanding changes to habitat conditions and contaminant transport.

Assessing forest fire dynamics and risk zones in Central Indian forests: a comparative study of the Khandwa and North Betul forest divisions of Madhya Pradesh.

Forest fires pose significant environmental and socioeconomic threats, particularly in regions such as Central India, where forest ecosystems are vital for biodiversity and local livelihoods. Understanding forest fire dynamics and identifying fire risk zones are crucial for effective mitigation. The current study explores the spatiotemporal dynamics of forest fires in the Khandwa and North Betul forest divisions in the Central Indian region over 22 years using Mann-Kendall and Sen's slope tests on MODIS (Moderate Resolution Imaging Spectroradiometer) fire point data. We found a nonsignificant increase in forest fires in both divisions. Khandwa showed a nonsignificant slope rise of more than three events per year, while North Betul revealed an increase of around one event per year. The lack of statistical significance suggests that upward trends of forest fire events may result from random fluctuations rather than consistent patterns. Spatial autocorrelation analysis revealed significant clustering of fire incidents in both regions. Khandwa confirmed moderate clustering (Moran's I = 0.043), whereas North Betul showed robust clustering (Moran's I = 0.096). Kernel density estimation further identified high-risk clusters in both divisions, necessitating zonal-wise targeted fire management strategies. Fire risk zonation was developed using the analytic hierarchy process (AHP), combining 10 environmental and socioeconomic factors. The AHP model, validated using MODIS fire data, showed reliable accuracy. The results revealed many of both divisions in the high- to very high-risk categories. Approximately, 45% of the area of the Khandwa and nearly 50% of the area of North Betul fall under high to very high fire risk zones. Khandwa's high-risk areas mainly lie in the northern and southeastern parts, while North Betul lies in the northwestern and north-eastern regions. The identified fire-prone areas indicate the pressing need for local or region-specific fire prevention and mitigation strategies. Thus, the findings of this study provide valuable insights into forest fire risk management and contribute to more focused research and methodological developments.

Logic of the Temporal Compartmentalization of the Hepatic Metabolic Cycle.

The mammalian liver must cope with various metabolic and physiological changes that normally recur every day and result primarily from rest-activity and fasting-feeding cycles. In this article, I present evidence supporting a temporal compartmentalization of rhythmic hepatic metabolic processes into four main clusters: regulation of energy homeostasis, maintenance of information integrity, immune response, and genetic information flow. I further review literatures and discuss how both the circadian and the newly discovered 12-h ultradian clock work together to regulate these four temporally separated processes in mouse liver, which, interestingly, is largely uncoupled from the liver zonation regulation.

In-Depth Quantification of Cell Division and Elongation Dynamics at the Tip of Growing Arabidopsis Roots Using 4D Microscopy, AI-Assisted Image Processing and Data Sonification.

One of the fundamental questions in plant developmental biology is how cell proliferation and cell expansion coordinately determine organ growth and morphology. An amenable system to address this question is the Arabidopsis root tip, where cell proliferation and elongation occur in spatially separated domains, and cell morphologies can easily be observed using a confocal microscope. While past studies revealed numerous elements of root growth regulation including gene regulatory networks, hormone transport and signaling, cell mechanics and environmental perception, how cells divide and elongate under possible constraints from cell lineages and neighboring cell files has not been analyzed quantitatively. This is mainly due to the technical difficulties in capturing cell division and elongation dynamics at the tip of growing roots, as well as an extremely labor-intensive task of tracing the lineages of frequently dividing cells. Here, we developed a motion-tracking confocal microscope and an Artificial Intelligence (AI)-assisted image-processing pipeline that enables semi-automated quantification of cell division and elongation dynamics at the tip of vertically growing Arabidopsis roots. We also implemented a data sonification tool that facilitates human recognition of cell division synchrony. Using these tools, we revealed previously unnoted lineage-constrained dynamics of cell division and elongation, and their contribution to the root zonation boundaries.