Liquid-Liquid Phase Separation Phenomenon on Protein Sorting Within Chloroplasts

In higher plants, chloroplasts are vital organelles possessing highly complex compartmentalization. As most chloroplast-located proteins are encoded in the nucleus and synthesized in the cytosol, the correct sorting of these proteins to appropriate compartments is critical for the proper functions of chloroplasts as well as plant survival. Nuclear-encoded chloroplast proteins are imported into stroma and further sorted to distinct compartments via different pathways. The proteins predicted to be sorted to the thylakoid lumen by the chloroplast twin arginine transport (cpTAT) pathway are shown to be facilitated by STT1/2 driven liquid-liquid phase separation (LLPS). Liquid-liquid phase separation is a novel mechanism to facilitate the formation of membrane-less sub-cellular compartments and accelerate biochemical reactions temporally and spatially. In this review, we introduce the sorting mechanisms within chloroplasts, and briefly summarize the properties and significance of LLPS, with an emphasis on the novel function of LLPS in the sorting of cpTAT substrate proteins. We conclude with perspectives for the future research on chloroplast protein sorting and targeting mechanisms.

CRITICAL REVIEW ON THE CONCEPT OF JATARAGNI

Proper functions of Agni (fire) in the body signify good health of the individual while an abnormal state leads to manifestations of diseases. The word Jatara means Udara (abdomen) and the Agni located in Jatara is Jataragni (digestive fire) and its Pramana (quantity) differs in each organism. There are various anatomical structures relat- ed to Jataragni that contribute towards its normal functioning. The physiological process of digestion and metab- olism including biophysical and biochemical changes in the ingested food is carried out by the influence of Jata- ragni. It also influences the status of Dosha, Dhatu and Mala in the body. The objective of this study is to know the anatomical and physiological aspects of Jataragni to understand the pathological states in the body. Keywords: Agni; Jataragni; Koshtanga; Grahani.

The Most Common Functional Disorders and Factors Affecting Female Pelvic Floor

The pelvic floor (PF) is made of muscles, ligaments, and fascia, which ensure organ statics, maintain muscle tone, and are involved in contractions. This review describes the myofascial relationships of PF with other parts of the body that determine the proper functions of PF, and also provides insight into PF disorders and the factors contributing to them. PF plays an important role in continence, pelvic support, micturition, defecation, sexual function, childbirth, and locomotion, as well as in stabilizing body posture and breathing, and cooperates with the diaphragm and postural muscles. In addition, PF associates with distant parts of the body, such as the feet and neck, through myofascial connections. Due to tissue continuity, functional disorders of muscles, ligaments, and fascia, even in the areas that are distant from PF, will lead to PF disorders, including urinary incontinence, fecal incontinence, prolapse, sexual dysfunction, and pain. Dysfunctions of PF will also affect the rest of the body.

An Overview of the Primary Cilium and RPGRIP1L: The Signalling Hub’s Anchor for Organ Development and Homeostasis

Research on the primary cilium has been growing exponentially in the past several decades due to its functions as a cell signalling hub, which defects leads to several disorders and abnormalities collectively known as ciliopathies. Among other parts of the primary cilium structures, the transition zone is the area whose defects lead to the most severe clinical manifestations and high lethality. The ciliary transition zone consists of multiple protein modules that are hypothesized to be anchored by the RPGRIP1L protein. Despite its importance, RPGRIP1L studies remain hidden from the limelight, and our understanding of the protein remains scattered. This review summarizes the clinical manifestations and molecular mechanisms of the RPGRIP1L in the primary cilium. We then take a closer look at each RPGRIP1L’s protein domain to understand how each domain ensures proper functions and localization of RPGRIP1L. The three domains of RPGRIP1L are postulated to be involved in different roles. While the coiled coil domain is vital for scaffolding the protein to the centriolar structure, the ability of the C2 domain to interact with lipid allows the formation of ‘lipid gate’ at the transition zone. The high variability of the RPGR interaction domain enable the RPGRIP1L to interact with multiple different proteins, making it an ideal anchor for other ciliary protein modules in the transition zone.

A genetic bottleneck of mitochondrial DNA during human lymphocyte development

Mitochondria are essential organelles in eukaryotic cells that provide critical support for energetic and metabolic homeostasis. Mutations that accumulate in mitochondrial DNA (mtDNA) in somatic cells have been implicated in cancer, degenerative diseases, and the aging process. However, the mechanisms used by somatic cells to maintain proper functions despite their mtDNA mutation load are poorly understood. Here, we analyzed somatic mtDNA mutations in more than 30,000 human single peripheral and bone marrow mononuclear cells and observed a significant overrepresentation of homoplastic mtDNA mutations in B, T and NK lymphocytes despite their lower mutational burden than other hematopoietic cells. The characteristic mutational landscape of mtDNA in lymphocytes were validated with data from multiple platforms and individuals. Single-cell RNA-seq and computational modeling demonstrated a stringent mitochondrial bottleneck during lymphocyte development likely caused by lagging mtDNA replication relative to cell proliferation. These results illuminate a potential mechanism used by highly metabolically active immune cells for quality control of their mitochondrial genomes.

Charging Up the Periphery: Glial Ionic Regulation in Sensory Perception

The peripheral nervous system (PNS) receives diverse sensory stimuli from the environment and transmits this information to the central nervous system (CNS) for subsequent processing. Thus, proper functions of cells in peripheral sense organs are a critical gate-keeper to generating appropriate animal sensory behaviors, and indeed their dysfunction tracks sensory deficits, sensorineural disorders, and aging. Like the CNS, the PNS comprises two major cell types, neurons (or sensory cells) and glia (or glia-like supporting neuroepithelial cells). One classic function of PNS glia is to modulate the ionic concentration around associated sensory cells. Here, we review current knowledge of how non-myelinating support cell glia of the PNS regulate the ionic milieu around sensory cell endings across species and systems. Molecular studies reviewed here suggest that, rather than being a passive homeostatic response, glial ionic regulation may in fact actively modulate sensory perception, implying that PNS glia may be active contributors to sensorineural information processing. This is reminiscent of emerging studies suggesting analogous roles for CNS glia in modulating neural circuit processing. We therefore suggest that deeper molecular mechanistic investigations into critical PNS glial functions like ionic regulation are essential to comprehensively understand sensorineural health, disease, and aging.

Hotair and Malat1 Long Noncoding RNAs regulate Bdnf Expression and Oligodendrocyte Precursor Cells Differentiation

BDNF has remarkable protective roles in the central nervous system to ensure neurons and glial cell survival and proper functions. The regulatory processes behind the BDNF expression have not been revealed completely. Here, it was explored whether Malat1 and Hotair lncRNAs play roles in the regulation of Bdnf expression level, modification of fingolimod downstream pathway, and oligodendrocytes precursor cells maturation. By Hotair and Malat1 downregulation, their regulatory mechanism on Bdnf expression was investigated. Immunostaining and RT-qPCR assays were employed to assess the effects of fingolimod and lncRNAs on OPCs maturation. The results represented that Hotair and Malat1 lncRNAs may regulate Bdnf expression in primary glial cells significantly, and also can coordinate fingolimod stimulatory effect on Bdnf expression. Furthermore, Malat1 may have a role in the last stages of the intrinsic oligodendrocyte myelination. Here it was demonstrated that these lncRNAs have critical roles in the Bdnf level, fingolimod mechanism of action, and OPCs maturation. Understanding the regulatory mechanism of neurotrophins leads to a better comprehension of the pathogenesis of the neurodegenerative disorder and designing more effective treatments.

Fucoidan from Sargassum Hemiphyllum Inhibits Infection and Inflammation of Helicobacter Pylori

When infected by Helicobacter pylori, it often causes gastritis, gastric ulcer, or gastric cancer. Antibiotics are used to treat H. pylori infection, as they inhibit or kill H. pylori often ex-tending to reduce the incidences of gastric adenoma and cancer. However, H. pylori has developed drug resistance to many clinically used antibiotics over the years, thereby providing no warranty of successful treatment whenever H. pylori infection befalls. We report here that fucoidan from Sargassumhemiphyllum can effectively reduce infection of H. pylori without development of drug resistance. Fucoidan demonstrated a strong anti-inflammation activity in RAW264.7 cell model. Using AGS cell model, fucoidan decreased H. pylori adhesion to host cells and thus reduced its infection rate, especially in post-treatment where the infection rate was reduced to 40%. Mechanistically, fucoidan intervenes the proper functions of adhesion molecules BabA and AlpA of H. pylori. Moreover, fucoidan is able to significantly lower the total count of H. pylori and the levels of IL-6 and TNF-α in vivo. Added together, these convergent results suggest that fucoidan is an effective agent in a position to protect stomach from H. pylori infection by reducing its total count and induced inflammation.

A Genetic Titration of Membrane Composition in C. elegans Reveals its Importance for Multiple Cellular and Physiological Traits

The composition and biophysical properties of cellular membranes must be tightly regulated to maintain the proper functions of myriad processes within cells. To better understand the importance of membrane homeostasis, we assembled a panel of five C. elegans strains that show a wide span of membrane composition and properties, ranging from excessively rich in saturated fatty acids (SFAs) and rigid to excessively rich in polyunsaturated fatty acids (PUFAs) and fluid. The genotypes of the five strain are, from most rigid to most fluid: paqr-1(tm3262);paqr-2(tm3410), paqr-2(tm3410), N2 (wild-type), mdt-15(et14);nhr-49(et8), and mdt-15(et14);nhr-49(et8);acs-13(et54). We confirmed the excess SFA/rigidity-to-excess PUFA/fluid gradient using the methods of fluorescence recovery after photobleaching (FRAP) and lipidomics analysis. The five strains were then studied for a variety of cellular and physiological traits and found to exhibit defects in: permeability, lipid peroxidation, growth at different temperatures, tolerance to SFA-rich diets, lifespan, brood size, vitellogenin trafficking, oogenesis and autophagy during starvation. The excessively rigid strains often exhibited defects in opposite directions compared to the excessively fluid strains. We conclude that deviation from wild-type membrane homeostasis is pleiotropically deleterious for numerous cellular/physiological traits. The strains introduced here should prove useful to further study the cellular and physiological consequences of impaired membrane homeostasis.

Alterations of Golgi Structural Proteins and Glycosylation Defects in Cancer

As the central hub in the secretory and endocytic pathways, the Golgi apparatus continually receives the flow of cargos and serves as a major processing station in the cell. Due to its dynamic nature, a sophisticated and constantly remodeling mechanism needs to be set up to maintain the Golgi architecture and function in the non-stop trafficking of proteins and lipids. Abundant evidence has been accumulated that a well-organized Golgi structure is required for its proper functions, especially protein glycosylation. Remarkably, altered glycosylation has been a hallmark of most cancer cells. To understand the causes of Golgi defects in cancer, efforts have been made to characterize Golgi structural proteins under physiological and pathological conditions. This review summarizes the current knowledge of crucial Golgi structural proteins and their connections with tumor progression. We foresee that understanding the Golgi structural and functional defects may help solve the puzzle of whether glycosylation defect is a cause or effect of oncogenesis.