•Coordinated calcium transport processes produce Ca2+ signatures in plant cells.•Magnesium transporters acquire and distribute Mg2+ throughout the plant.•CBL-CIPK signaling networks link calcium and ...magnesium homeostasis together.
Calcium (Ca2+) and magnesium (Mg2+) are the most abundant divalent cations in plants. As a nutrient and a signaling ion, Ca2+ levels in the cell are tightly controlled by an array of channels and carriers that provide mechanistic basis for Ca2+ homeostasis and the generation of Ca2+ signals. Although a family of CorA-type Mg2+ transporters plays a key role in controlling Mg2+ homeostasis in plants, more components are yet to be identified. Ca2+ and Mg2+ appear to have antagonistic interactions in plant cells, and therefore plants depend on a homeostatic balance between Ca2+ and Mg2+ for optimal growth and development. Maintenance of such a balance in response to changing nutrient status in the soil emerges as a critical feature of plant mineral nutrition. Studies have uncovered signaling mechanisms that perceive nutrient status as a signal and regulate transport activities as adaptive responses. This ‘nutrient sensing’ network is exemplified by the Ca2+-dependent CBL (calcineurin B-like)-CIPK (CBL-interacting protein kinase) pathway that serves as a major link between environmental nutrient status and transport activities. In this review, we analyze the recent literature on Ca2+ and Mg2+ transport systems and their regulation and provide our perspectives on future research.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Calcium (Ca2+) serves as an essential nutrient as well as a signaling agent in all eukaryotes. In plants, calcineurin B-like proteins (CBLs) are a unique group of Ca2+ sensors that decode Ca2+ ...signals by activating a family of plant-specific protein kinases known as CBL-interacting protein kinases (CIPKs). Interactions between CBLs and CIPKs constitute a signaling network that enables information integration and physiological coordination in response to a variety of extracellular cues such as nutrient deprivation and abiotic stresses. Studies in the past two decades have established a unified paradigm that illustrates the functions of CBL–CIPK complexes in controlling membrane transport through targeting transporters and channels in the plasma membrane and tonoplast.
A novel type of Ca2+ sensors, termed as calcineurin B-like proteins (CBLs), were identified in plant cells 20 years ago. They specifically target a family of plant-specific CBL-interacting protein kinases (CIPKs).To decode a Ca2+ signal, CBL binds Ca2+ and interacts with CIPK, leading to activation of the kinase. The CBL–CIPK complex phosphorylates downstream target proteins and changes their biological activities.Most CBL proteins are localized to the cell membranes and, as a result, CBL–CIPK complexes are largely associated with membranes. This unique feature underlies the core function of the CBL–CIPK network in regulating various membrane transport processes in the plasma membrane and the tonoplast, thereby linking Ca2+ signaling to plant nutrient sensing and homeostasis.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
3.
Long-Term Efficacy of a Hepatitis E Vaccine Zhang, Jun; Zhang, Xue-Feng; Huang, Shou-Jie ...
New England journal of medicine/The New England journal of medicine,
03/2015, Volume:
372, Issue:
10
Journal Article
Peer reviewed
Open access
Hepatitis E virus is a common cause of illness worldwide and is associated with severe complications, especially in pregnant women. In this report, the long-term efficacy, immunogenicity, and safety ...of a hepatitis E vaccine are described.
Hepatitis E virus (HEV) is a common cause of acute hepatitis worldwide.
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HEV infection occurs in two distinct epidemiologic patterns.
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The most common pattern is waterborne infection, which is caused by HEV genotype 1 or 2 and occurs mainly in resource-limited countries, often in large, protracted outbreaks or in sporadic cases associated with high mortality among pregnant women.
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The other pattern is transmission from animals and humans, which is caused by HEV genotype 3 or 4 and occurs widely in both resource-limited and developed countries.
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Rein et al.
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estimated the incidence of hepatitis E in areas . . .
Under low-potassium (K
) stress, a Ca
signaling network consisting of calcineurin B-like proteins (CBLs) and CBL-interacting kinases (CIPKs) play essential roles. Specifically, the plasma membrane ...CBL1/9-CIPK pathway and the tonoplast CBL2/3-CIPK pathway promotes K
uptake and remobilization, respectively, by activating a series of K
channels. While the dual CBL-CIPK pathways enable plants to cope with low-K
stress, little is known about the early events that link external K
levels to the CBL-CIPK proteins. Here we show that K
status regulates the protein abundance and phosphorylation of the CBL-CIPK-channel modules. Further analysis revealed low K
-induced activation of VM-CBL2/3 happened earlier and was required for full activation of PM-CBL1/9 pathway. Moreover, we identified CIPK9/23 kinases to be responsible for phosphorylation of CBL1/9/2/3 in plant response to low-K
stress and the HAB1/ABI1/ABI2/PP2CA phosphatases to be responsible for CBL2/3-CIPK9 dephosphorylation upon K
-repletion. Further genetic analysis showed that HAB1/ABI1/ABI2/PP2CA phosphatases are negative regulators for plant growth under low-K
, countering the CBL-CIPK network in plant response and adaptation to low-K
stress.
Two types of tonoplast proton pumps, H⁺-pyrophosphatase (V-PPase) and the H⁺-ATPase (V-ATPase), establish the proton gradient that powers molecular traffic across the tonoplast thereby facilitating ...turgor regulation and nutrient homeostasis. However, how proton pumps regulate development remains unclear.
In this study, we investigated the function of two types of proton pumps in Arabidopsis embryo development and pattern formation. While disruption of either V-PPase or V-ATPase had no obvious effect on plant embryo development, knocking out both resulted in severe defects in embryo pattern formation from the early stage.
While the first division in wild-type zygote was asymmetrical, a nearly symmetrical division occurred in the mutant, followed by abnormal pattern formation at all stages of embryo development. The embryonic defects were accompanied by dramatic differences in vacuole morphology and distribution, as well as disturbed localisation of PIN1. The development of mutant cotyledons and root, and the auxin response of mutant seedlings supported the hypothesis that mutants lacking tonoplast proton pumps were defective in auxin transport and distribution.
Taking together, we proposed that two tonoplast proton pumps are required for vacuole morphology and PIN1 localisation, thereby controlling vacuole and auxin-related developmental processes in Arabidopsis embryos and seedlings.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NMLJ, NUK, OILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
Significance Plant growth requires a balanced supply of mineral nutrients. However, the availability of minerals varies constantly in the environment. How do plants adapt to low or high levels of ...minerals in the soil? The answer to this question holds the key to sustainable crop production. Mg is an essential macronutrient for plants, but high levels of Mg ²⁺ can become toxic. This study uncovered a regulatory mechanism, consisting of two calcineurin B-like (CBL) Ca sensors partnering with four CBL-interacting protein kinases (CIPKs) forming a CBL–CIPK network that allows plant cells to sequester the extra Mg ²⁺ into vacuoles, thereby protecting plant cells from high-Mg toxicity. To our knowledge, this report is the first that describes such a signaling mechanism for regulation of Mg homeostasis.
Although Mg ²⁺ is essential for a myriad of cellular processes, high levels of Mg ²⁺ in the environment, such as those found in serpentine soils, become toxic to plants. In this study, we identified two calcineurin B-like (CBL) proteins, CBL2 and CBL3, as key regulators for plant growth under high-Mg conditions. The Arabidopsis mutant lacking both CBL2 and CBL3 displayed severe growth retardation in the presence of excess Mg ²⁺, implying elevated Mg ²⁺ toxicity in these plants. Unexpectedly, the cbl2 cbl3 mutant plants retained lower Mg content than wild-type plants under either normal or high-Mg conditions, suggesting that CBL2 and CBL3 may be required for vacuolar Mg ²⁺ sequestration. Indeed, patch-clamp analysis showed that the cbl2 cbl3 mutant exhibited reduced Mg ²⁺ influx into the vacuole. We further identified four CBL-interacting protein kinases (CIPKs), CIPK3, -9, -23, and -26, as functionally overlapping components downstream of CBL2/3 in the signaling pathway that facilitates Mg ²⁺ homeostasis. The cipk3 cipk9 cipk23 cipk26 quadruple mutant, like the cbl2 cbl3 double mutant, was hypersensitive to high-Mg conditions; furthermore, CIPK3/9/23/26 physically interacted with CBL2/3 at the vacuolar membrane. Our results thus provide evidence that CBL2/3 and CIPK3/9/23/26 constitute a multivalent interacting network that regulates the vacuolar sequestration of Mg ²⁺, thereby protecting plants from Mg ²⁺ toxicity.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Multiple transporters and channels mediate cation transport across the plasma membrane and tonoplast to regulate ionic homeostasis in plant cells. However, much less is known about the molecular ...function of transporters that facilitate cation transport in other organelles such as Golgi. We report here that Arabidopsis KEA4, KEA5, and KEA6, members of cation/proton antiporters‐2 (CPA2) superfamily were colocalized with the known Golgi marker, SYP32‐mCherry. Although single kea4,5,6 mutants showed similar phenotype as the wild type under various conditions, kea4/5/6 triple mutants showed hypersensitivity to low pH, high K+, and high Na+ and displayed growth defects in darkness, suggesting that these three KEA‐type transporters function redundantly in controlling etiolated seedling growth and ion homeostasis. Detailed analysis indicated that the kea4/5/6 triple mutant exhibited cell wall biosynthesis defect during the rapid etiolated seedling growth and under high K+/Na+ condition. The cell wall‐derived pectin homogalacturonan (GalA)3 partially suppressed the growth defects and ionic toxicity in the kea4/5/6 triple mutants when grown in the dark but not in the light conditions. Together, these data support the hypothesis that the Golgi‐localized KEAs play key roles in the maintenance of ionic and pH homeostasis, thereby facilitating Golgi function in cell wall biosynthesis during rapid etiolated seedling growth and in coping with high K+/Na+ stress.
Plastidial K+ transporters KEA1, KEA2, and KEA3 have been reported to play important roles in chloroplast osmoregulation, integrity, and pH regulation in Arabidopsis. However, much less is known about the molecular identity and function of KEA4, KEA5, and KEA6. In our report, we demonstrate that the Golgi‐localized KEA4, KEA5, and KEA6 play key roles in the maintenance of ionic and pH homeostasis, thereby facilitating Golgi function in cell wall biosynthesis during rapid cell growth of etiolated seedlings and in coping with high K+/Na+ stress. This study represents the first functional analysis of these three transporters in any plant species.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Light‐sheet fluorescence microscopy (LSFM), sectioning biological samples by illuminating a thin slice of fluorescently labelled live cells or tissues typically with a Bessel beam, requires dithering ...the beam to form a two‐dimensional (2D) light sheet. It usually suffers from severe phototoxicity and low signal‐to‐noise ratio (SNR) mainly caused by the side‐lobe illumination generating unfavorable bio‐fluorescence from the adjacent tissues. Here, the first proof‐of‐concept experimental implementation of genetic algorithm (GA) generated metalens is provided to address the above challenges. It is shown that a dithering‐free 2D light sheet produced by a GaN‐based metalens with GA‐generated prism‐like yet non‐analytical phase profile, can significantly suppress the side‐lobe intensity of the resultant light sheet down to 7.3% of the main lobe intensity and also extends its depth of focus up to 4 mm, surpassing the latest results reported in the literature. When applied under two‐photon excitation, the light sheet exhibits an enhanced axial resolution and SNR. These results demonstrate the feasibility of applying artificial intelligence generated metalens in addressing some special issues encountered by conventional analytical design approaches, and the metalens device produced here could find an important role in fast‐LSFM‐based large‐scale bioimaging applications without mechanical dithering.
Experimental implementation demonstrates that a genetic algorithm (GA) generated one‐dimensional (1D) non‐analytical phase profile can be assianged to a gallium nitride (GaN)‐based metalens, to produce a 4 mm long two‐dimensional (2D) non‐diffractive optical pattern with significant side‐lobe suppression, which can promisingly address some of the typical issues encountered by conventional Gaussian beam or Bessel beam based light sheet fluorescence microscopy.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Plant responses to developmental and environmental cues are often mediated by calcium （Ca2＋） signals that are transmitted by diverse calcium sensors. The calcineurin B-like （CBL） protein family ...represents calcium sensors that decode calcium signals through specific interactions with a group of CBL-interacting protein kinases. We report functional analysis ofArabidopsis CBL2 and CBL3, two closely related CBL members that are localized to the vacuolar membrane through the N-terminal tonoplast-targeting sequence. While cbl2 or cbl3 single mutant did not show any phenotypic difference from the wild type, the cbl2 cbl3 double mutant was stunted with leaf tip necrosis, under- developed roots, shorter siliques and fewer seeds. These defects were reminiscent of those in the vha-a2 vha-a3 double mutant deficient in vacuolar H＋-ATPase （V-ATPase）. Indeed, the V-ATPase activity was reduced in the cbl2 cbl3 double mutant, connecting tonoplast CBL-type calcium sensors to the regulation of V-ATPase. Furthermore, cbl2 cbl3 double mutant was compromised in ionic tolerance and micronutrient accumulation, consistent with the defect in V-ATPase activity that has been shown to function in ion compartmentalization. Our results suggest that calcium sensors CBL2 and CBL3 serve as molecular links between calcium signaling and V-ATPase, a central regulator of in- tracellular ion homeostasis.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The anterior pituitary gland plays a central role in regulating various physiological processes, including body growth, reproduction, metabolism and stress response. Here, we perform single-cell ...RNA-sequencing (scRNA-seq) of 4113 individual cells from human fetal pituitaries. We characterize divergent developmental trajectories with distinct transitional intermediate states in five hormone-producing cell lineages. Corticotropes exhibit an early intermediate state prior to full differentiation. Three cell types of the PIT-1 lineage (somatotropes, lactotropes and thyrotropes) segregate from a common progenitor coexpressing lineage-specific transcription factors of different sublineages. Gonadotropes experience two multistep developmental trajectories. Furthermore, we identify a fetal gonadotrope cell subtype expressing the primate-specific hormone chorionic gonadotropin. We also characterize the cellular heterogeneity of pituitary stem cells and identify a hybrid epithelial/mesenchymal state and an early-to-late state transition. Here, our results provide insights into the transcriptional landscape of human pituitary development, defining distinct cell substates and subtypes and illustrating transcription factor dynamics during cell fate commitment.
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