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1.
Receptor-Like Kinases Sustain Symbiotic Scrutiny.
Chiu, CH, Paszkowski, U
Plant physiology. 2020;(4):1597-1612
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Abstract
Plant receptor-like kinases (RLKs) control the initiation, development, and maintenance of symbioses with beneficial mycorrhizal fungi and nitrogen-fixing bacteria. Carbohydrate perception activates symbiosis signaling via Lysin-motif RLKs and subsequently the common symbiosis signaling pathway. As the receptors activated are often also immune receptors in multiple species, exactly how carbohydrate identities avoid immune activation and drive symbiotic outcome is still not fully understood. This may involve the coincident detection of additional signaling molecules that provide specificity. Because of the metabolic costs of supporting symbionts, the level of symbiosis development is fine-tuned by a range of local and mobile signals that are activated by various RLKs. Beyond early, precontact symbiotic signaling, signal exchanges ensue throughout infection, nutrient exchange, and turnover of symbiosis. Here, we review the latest understanding of plant symbiosis signaling from the perspective of RLK-mediated pathways.
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The Evolving Complexity of Treating Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor-2 (HER2)-Negative Breast Cancer: Special Considerations in Older Breast Cancer Patients-Part I: Early-Stage Disease.
Sammons, S, Sedrak, MS, Kimmick, GG
Drugs & aging. 2020;(5):331-348
Abstract
The median age for breast cancer diagnosis is 62 years, but a disproportionate number of patients are over the age of 75 years and the majority of those have hormone receptor-positive, human epidermal growth factor receptor-2 (HER2)-negative cancers. This review provides a logical algorithm to guide providers through the many complicated issues involved in adjuvant systemic therapy decisions in older patients with hormone receptor-positive, HER2-negative breast cancer. For this subtype of breast cancer, the mainstay of treatment is surgery and adjuvant endocrine therapy with tamoxifen or an aromatase inhibitor (AI). Adjuvant chemotherapy is added to the treatment regimen when the benefits of treatment are deemed to outweigh the risks, making the risk-benefit discussion particularly important in older women. Traditional tools for cancer risk assessment and genomic expression profiles (GEPs) are under-utilized in older patients, but yield equally useful information about cancer prognosis as they do in younger patients. Additionally, there are tools that estimate life-limiting toxicity risk from chemotherapy and life expectancy, which are both important issues in the risk-benefit discussion. For very low-risk cancers, such as non-invasive and small lymph node (LN)-negative cancers, the benefits of any adjuvant therapy is likely outweighed by the risks, but endocrine therapy might be considered to prevent future new breast cancers. For invasive tumors that are > 5 mm (T1b or larger) or involve LNs, adjuvant endocrine therapy is recommended. Generally, AIs should be included, though tamoxifen is effective and should be offered when AIs are not tolerated. Bone-preserving agents and high-dose vitamin D are options to preserve bone density or treat osteoporosis, especially in older women who are taking AIs. Where the risk-reducing benefit from adjuvant chemotherapy outweighs the toxicity risk, adjuvant chemotherapy should be considered. Adjuvant chemotherapy has similar benefits in older and younger patients and standard regimens are preferred. Several exciting clinic trials are underway and have included older patients, including those adding molecularly targeted agents, cyclin-dependent kinase (CDK) 4/6 inhibitors and everolimus, to endocrine therapy in the adjuvant setting. The high incidence of breast cancer in older women should drive us to design clinical trials for this population and emphasize their inclusion in ongoing trials as much as possible.
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Clinical, genetic, and molecular characterization of hyperphosphatasia with mental retardation: a case report and literature review.
Abi Farraj, L, Khatoun, WD, Abou Chebel, N, Wakim, V, Dawali, K, Ghassibe-Sabbagh, M
Diagnostic pathology. 2019;(1):123
Abstract
BACKGROUND Hyperphosphatasia with mental retardation syndrome (HPMRS) is a recessive disorder characterized by high blood levels of alkaline phosphatase together with typical dysmorphic signs such as cleft palate, intellectual disability, cardiac abnormalities, and developmental delay. Genes involved in the glycosylphosphatidylinositol pathway and known to be mutated in HPMRS have never been characterized in the Lebanese population. CASE PRESENTATION Herein, we describe a pair of monozygotic twins presenting with severe intellectual disability, distinct facial dysmorphism, developmental delay, and increased alkaline phosphatase level. Two individuals underwent whole exome sequencing followed by Sanger sequencing to confirm the co-segregation of the mutation in the consanguineous family. A biallelic loss of function mutation in PGAP3 was detected. Both patients were homozygous for the c.203delC (p.C68LfsX88) mutation and the parents were carriers confirming the founder effect of the mutation. High ALP serum levels confirmed the molecular diagnosis. CONCLUSION Our findings have illustrated the genomic profile of PGAP3-related HPMRS which is essential for targeted molecular and genetic testing. Moreover, we found previously unreported clinical findings such as hypodontia and skin hyperpigmentation. These features, together with the novel mutation expand the phenotypic and genotypic spectrum of this rare recessive disorder.
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4.
Platelet Apoptosis Can Be Triggered Bypassing the Death Receptors.
Leytin, V, Gyulkhandanyan, AV, Freedman, J
Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis. 2019;:1076029619853641
Abstract
In nucleated cells, the extrinsic pathway of the programmed cell death (apoptosis) is triggered by interaction of death ligands of the tumor necrosis factor superfamily with the death receptors on external cell surface membrane. In this review, we present evidence that, in contrast to nucleated cells, apoptosis in anucleate platelets can be induced through bypassing the death receptors, using instead specific receptors on the platelet surface mediating platelet activation, aggregation, and blood coagulation. These platelet surface receptors include the protease-activated receptor 1 of thrombin and glycoproteins IIbIIIa and Ibα, receptors of fibrinogen, and von Willebrand factor. The pro-apoptotic BH3 mimetic ABT-737 and calcium ionophore A23187 also trigger platelet apoptosis without using death receptors. These agents induce the intrinsic pathway of platelet apoptosis by direct targeting mitochondrial and extra-mitochondrial apoptotic responses.
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5.
Potential Astrocytic Receptors and Transporters in the Pathogenesis of Alzheimer's Disease.
Zhang, X, Lao, K, Qiu, Z, Rahman, MS, Zhang, Y, Gou, X
Journal of Alzheimer's disease : JAD. 2019;(4):1109-1122
Abstract
Alzheimer's disease (AD) is the most common cause of dementia and is characterized by the progressive loss of memory and cognition in the aging population. However, the etiology of and therapies for AD remain far from understood. Astrocytes, the most abundant neuroglia in the brain, have recently aroused substantial concern due to their involvement in synaptotoxicity, amyloidosis, neuroinflammation, and oxidative stress. In this review, we summarize the candidate molecules of astrocytes, especially receptors and transporters, that may be involved in AD pathogenesis. These molecules include excitatory amino acid transporters (EAATs), metabotropic glutamate receptor 5 (mGluR5), the adenosine 2A receptor (A2AR), the α7-nicotinic acetylcholine receptor (α7-nAChR), the calcium-sensing receptor (CaSR), S100β, and cannabinoid receptors. We describe the characteristics of these molecules and the neurological and pharmacological underpinnings of these molecules in AD. Among these molecules, EAATs, A2AR, and mGluR5 are strongly related to glutamate-mediated synaptotoxicity and are involved in glutamate transmission or the clearance of extrasynaptic glutamate in the AD brain. The α7-nAChR, CaSR, and mGluR5 are receptors of Aβ and can induce a plethora of toxic effects, such as the production of excess Aβ, synaptotoxicity, and NO production triggered by changes in intracellular calcium signaling. Antagonists or positive allosteric modulators of these receptors can repair cognitive ability and modify neurobiological changes. Moreover, blocking S100β or activating cannabinoid receptors reduces neuroinflammation, oxidative stress, and reactive astrogliosis. Thus, targeting these molecules might provide alternative approaches for treating AD.
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6.
Light and temperature cues: multitasking receptors and transcriptional integrators.
Casal, JJ, Qüesta, JI
The New phytologist. 2018;(3):1029-1034
Abstract
Contents Summary 1029 I. Introduction 1029 II. Convergence at the receptor 1030 III. Convergence at transcriptional hubs 1031 IV. Convergence involving clock components 1033 V. Conclusions 1033 Acknowledgements 1033 References 1033 SUMMARY The combined information provided by light and temperature cues helps to optimise plant body architecture and physiology. Plants possess elaborate systems to sense and respond to these stimuli. Simultaneous perception of light and temperature by dual receptors such as phytochrome B and phototropin leads to immediate signalling convergence. Conversely, cue asynchronies initiate separate pathways and the information of the earliest cue is stored, awaiting the arrival of the later cue to control transcription. Storage mechanisms can involve changes in the activity of selected clock components or epigenetic modifications, depending on the time delay between cues (hours, days or several months). We propose a conceptual framework in which the mechanisms of integration relate to the timing of cue sensing.
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7.
Ethylene receptors and related proteins in climacteric and non-climacteric fruits.
Chen, Y, Grimplet, J, David, K, Castellarin, SD, Terol, J, Wong, DCJ, Luo, Z, Schaffer, R, Celton, JM, Talon, M, et al
Plant science : an international journal of experimental plant biology. 2018;:63-72
Abstract
Fruits have been traditionally classified into two categories based on their capacity to produce and respond to ethylene during ripening. Fruits whose ripening is associated to a peak of ethylene production and a respiration burst are referred to as climacteric, while those that are not are referred to as non-climacteric. However, an increasing body of literature supports an important role for ethylene in the ripening of both climacteric and non-climacteric fruits. Genome and transcriptomic data have become available across a variety of fruits and we leverage these data to compare the structure and transcriptional regulation of the ethylene receptors and related proteins. Through the analysis of four economically important fruits, two climacteric (tomato and apple), and two non-climacteric (grape and citrus), this review compares the structure and transcriptional regulation of the ethylene receptors and related proteins in both types of fruit, establishing a basis for the annotation of ethylene-related genes. This analysis reveals two interesting differences between climacteric and non-climacteric fruit: i) a higher number of ETR genes are found in climacteric fruits, and ii) non-climacteric fruits are characterized by an earlier ETR expression peak relative to sugar accumulation.
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8.
Cell-Surface and Nuclear Receptors in the Colon as Targets for Bacterial Metabolites and Its Relevance to Colon Health.
Sivaprakasam, S, Bhutia, YD, Ramachandran, S, Ganapathy, V
Nutrients. 2017;(8)
Abstract
The symbiotic co-habitation of bacteria in the host colon is mutually beneficial to both partners. While the host provides the place and food for the bacteria to colonize and live, the bacteria in turn help the host in energy and nutritional homeostasis, development and maturation of the mucosal immune system, and protection against inflammation and carcinogenesis. In this review, we highlight the molecular mediators of the effective communication between the bacteria and the host, focusing on selective metabolites from the bacteria that serve as messengers to the host by acting through selective receptors in the host colon. These bacterial metabolites include the short-chain fatty acids acetate, propionate, and butyrate, the tryptophan degradation products indole-3-aldehyde, indole-3-acetic, acid and indole-3-propionic acid, and derivatives of endogenous bile acids. The targets for these bacterial products in the host include the cell-surface G-protein-coupled receptors GPR41, GPR43, and GPR109A and the nuclear receptors aryl hydrocarbon receptor (AhR), pregnane X receptor (PXR), and farnesoid X receptor (FXR). The chemical communication between these bacterial metabolite messengers and the host targets collectively has the ability to impact metabolism, gene expression, and epigenetics in colonic epithelial cells as well as in mucosal immune cells. The end result, for the most part, is the maintenance of optimal colonic health.
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9.
The role of receptor-like protein kinases (RLKs) in abiotic stress response in plants.
Ye, Y, Ding, Y, Jiang, Q, Wang, F, Sun, J, Zhu, C
Plant cell reports. 2017;(2):235-242
Abstract
We review and introduce recent studies on RLK s involved in the abiotic stress response and provide insights into potential regulatory mechanisms for alleviating abiotic stress. Abiotic stresses are important factors affecting plant growth and development, resulting in crop production reduction and even plant death. To survive, plants utilize different mechanisms to respond and adapt to continuously changing environmental factors. Understanding of the molecular mechanisms of plant response to various stresses will aid in improving tolerance of plants to abiotic stress through genetic engineering, which would greatly promote the development of modern agriculture. RLKs, the largest gene family in plants, play critical roles in the regulation of plant developmental processes, signaling networks and disease resistance. Many RLKs have been shown to be involved in abiotic stress responses, including the abscisic acid response, calcium signaling and antioxidant defense. This review summarizes recent studies on RLKs involved in plant responses to abiotic stress, including drought, salt, cold, toxic metals/metalloids and other stresses, and emphasizes the upstream and downstream factors in RLK signal transduction pathways under abiotic stress.
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10.
Calcium Channels and Associated Receptors in Malignant Brain Tumor Therapy.
Morrone, FB, Gehring, MP, Nicoletti, NF
Molecular pharmacology. 2016;(3):403-9
Abstract
Malignant brain tumors are highly lethal and aggressive. Despite recent advances in the current therapies, which include the combination of surgery and radio/chemotherapy, the average survival rate remains poor. Altered regulation of ion channels is part of the neoplastic transformation, which suggests that ion channels are involved in cancer. Distinct classes of calcium-permeable channels are abnormally expressed in cancer and are likely involved in the alterations underlying malignant growth. Specifically, cytosolic Ca(2+) activity plays an important role in the regulation of cell proliferation, and Ca(2+) signaling is altered in proliferating tumor cells. A series of previous studies emphasized the importance of the T-type low-voltage-gated calcium channels (VGCC) in different cancer types, including gliomas, and remarkably, pharmacologic inhibition of T-type VGCC caused antiproliferative effects and triggered apoptosis of human glioma cells. Other calcium permeable channels, such as transient receptor potential (TRP) channels, contribute to changes in Ca(2+) by modulating the driving force for Ca(2+) entry, and some TRP channels are required for proliferation and migration in gliomas. Furthermore, recent evidence shows that TRP channels contribute to the progression and survival of the glioblastoma patients. Likewise, the purinergic P2X7 receptor acts as a direct conduit for Ca(2+)-influx and an indirect activator of voltage-gated Ca(2+)-channel. Evidence also shows that P2X7 receptor activation is linked to elevated expression of inflammation promoting factors, tumor cell migration, an increase in intracellular mobilization of Ca(2+), and membrane depolarization in gliomas. Therefore, this review summarizes the recent findings on calcium channels and associated receptors as potential targets to treat malignant gliomas.