scholarly journals Knockout Gene-Based Evidence for PIWI-Interacting RNA Pathway in Mammals

2021 ◽  
Vol 9 ◽  
Author(s):  
Yinuo Li ◽  
Yue Zhang ◽  
Mingxi Liu
Keyword(s):  
Germ Cells ◽  
Current Knowledge ◽  
Conditional Knockout ◽  
Evolutionarily Conserved ◽  
Cell Arrest ◽  
And Function ◽  
Knockout Animals ◽  
Pirna Pathway ◽  
Long Interspersed Nuclear Element ◽  
Knockout Gene

The PIWI-interacting RNA (piRNA) pathway mainly consists of evolutionarily conserved protein factors. Intriguingly, many mutations of piRNA pathway factors lead to meiotic arrest during spermatogenesis. The majority of piRNA factor-knockout animals show arrested meiosis in spermatogenesis, and only a few show post-meiosis male germ cell arrest. It is still unclear whether the majority of piRNA factors expressed in spermatids are involved in long interspersed nuclear element-1 repression after meiosis, but future conditional knockout research is expected to resolve this. In addition, recent hamster knockout studies showed that a piRNA factor is necessary for oocytes—in complete contrast to the findings in mice. This species discrepancy allows researchers to reexamine the function of piRNA in female germ cells. This mini-review focuses on the current knowledge of protein factors derived from mammalian knockout studies and summarizes their roles in the biogenesis and function of piRNAs.

scholarly journals Investigation of Cuprizone-Induced Demyelination in mGFAP-Driven Conditional Transient Receptor Potential Ankyrin 1 (TRPA1) Receptor Knockout Mice

Cells ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 81 ◽  
Author(s):  
Gábor Kriszta ◽  
Balázs Nemes ◽  
Zoltán Sándor ◽  
Péter Ács ◽  
Sámuel Komoly ◽  
...  
Keyword(s):  
Knockout Mice ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Conditional Knockout ◽  
Genetic Deletion ◽  
The Difference ◽  
Magnetic Resonance Imaging Mri ◽  
Transient Receptor ◽  
And Function ◽  
Knockout Animals

Transient receptor potential ankyrin 1 (TRPA1) receptors are non-selective cation channels responsive to a variety of exogenous irritants and endogenous stimuli including products of oxidative stress. It is mainly expressed by primary sensory neurons; however, expression of TRPA1 by astrocytes and oligodendrocytes has recently been detected in the mouse brain. Genetic deletion of TRPA1 was shown to attenuate cuprizone-induced oligodendrocyte apoptosis and myelin loss in mice. In the present study we aimed at investigating mGFAP-Cre conditional TRPA1 knockout mice in the cuprizone model. These animals were generated by crossbreeding GFAP-Cre+/− and floxed TRPA1 (TRPA1Fl/Fl) mice. Cuprizone was administered for 6 weeks and demyelination was followed by magnetic resonance imaging (MRI). At the end of the treatment, demyelination and glial activation was also investigated by histological methods. The results of the MRI showed that demyelination was milder at weeks 3 and 4 in both homozygous (GFAP-Cre+/− TRPA1Fl/Fl) and heterozygous (GFAP-Cre+/− TRPA1Fl/−) conditional knockout animals compared to Cre−/− control mice. However, by week 6 of the treatment the difference was not detectable by either MRI or histological methods. In conclusion, TRPA1 receptors on astrocytes may transiently contribute to the demyelination induced by cuprizone, however, expression and function of TRPA1 receptors by other cells in the brain (oligodendrocytes, microglia, neurons) warrant further investigation.

scholarly journals Cilia Distal Domain: Diversity in Evolutionarily Conserved Structures

Cells ◽  
2019 ◽  
Vol 8 (2) ◽  
pp. 160 ◽  
Author(s):  
Helena Soares ◽  
Bruno Carmona ◽  
Sofia Nolasco ◽  
Luís Viseu Melo ◽  
João Gonçalves
Keyword(s):  
Cell Surface ◽  
Current Knowledge ◽  
Intraflagellar Transport ◽  
Basic Structure ◽  
Structure And Function ◽  
Single Organism ◽  
Evolutionarily Conserved ◽  
And Function ◽  
High Degree ◽  
Structure Diversity

Eukaryotic cilia are microtubule-based organelles that protrude from the cell surface to fulfill sensory and motility functions. Their basic structure consists of an axoneme templated by a centriole/basal body. Striking differences in ciliary ultra-structures can be found at the ciliary base, the axoneme and the tip, not only throughout the eukaryotic tree of life, but within a single organism. Defects in cilia biogenesis and function are at the origin of human ciliopathies. This structural/functional diversity and its relationship with the etiology of these diseases is poorly understood. Some of the important events in cilia function occur at their distal domain, including cilia assembly/disassembly, IFT (intraflagellar transport) complexes’ remodeling, and signal detection/transduction. How axonemal microtubules end at this domain varies with distinct cilia types, originating different tip architectures. Additionally, they show a high degree of dynamic behavior and are able to respond to different stimuli. The existence of microtubule-capping structures (caps) in certain types of cilia contributes to this diversity. It has been proposed that caps play a role in axoneme length control and stabilization, but their roles are still poorly understood. Here, we review the current knowledge on cilia structure diversity with a focus on the cilia distal domain and caps and discuss how they affect cilia structure and function.

scholarly journals Ring 1 and YY1 Binding Protein is Expressed in Murine Spermatocytes but Dispensable for Spermatogenesis

Genes ◽  
2020 ◽  
Vol 11 (1) ◽  
pp. 84
Author(s):  
Zhen He ◽  
Rong-Ge Yan ◽  
Xiao-Na Zhang ◽  
Qi-En Yang
Keyword(s):  
Germ Cells ◽  
Normal Development ◽  
Binding Protein ◽  
Regulation Of Gene Expression ◽  
Polycomb Group ◽  
Conditional Knockout ◽  
Immunofluorescent Staining ◽  
Conditional Deletion ◽  
Important Regulator ◽  
And Function

Spermatogenesis is a complex cellular-differentiation process that relies on the precise regulation of gene expression in spermatogonia, meiotic, and postmeiotic germ cells. The Ring 1 and YY1 binding protein (Rybp) is a member of the mammalian polycomb-group (PcG) protein family that plays multifunctional roles in development. Previous findings indicate that Rybp may function as an important regulator of meiosis. However, its expression in the testes and function in spermatogenesis have not been examined. In this study, we investigated Rybp expression in postnatal mouse testes using qRT-PCR and immunohistochemistry. We also examined the function of Rybp in spermatogenesis by using a conditional-knockout approach. Results showed that the relative expression of Rybp mRNA was significantly upregulated in the testes of postnatal day (PD) 6 mice. Immunofluorescent staining revealed that Rybp was enriched in the spermatocytes. Surprisingly, a conditional deletion of Rybp in fetal germ cells did not affect the fertility or normal development of spermatogenic cells. Further analysis revealed that Rybp deletion resulted in a decreased expression of meiosis-related genes, but that meiosis progression was normal. Together, these findings suggest that Rybp expression was enriched in spermatocytes, but that it was not required for spermatogenesis.

scholarly journals Biomedical potential of mammalian spectraplakin proteins: Progress and prospect

2019 ◽  
Vol 244 (15) ◽  
pp. 1313-1322 ◽  
Author(s):  
Sarah A King ◽  
Han Liu ◽  
Xiaoyang Wu
Keyword(s):  
Current Knowledge ◽  
Essential Element ◽  
Eukaryotic Cell ◽  
Form And Function ◽  
Cellular Processes ◽  
Biological Phenomena ◽  
Evolutionarily Conserved ◽  
Inflammatory Bowel ◽  
Cytoskeletal Networks ◽  
And Function

The cytoskeleton is an essential element of a eukaryotic cell which informs both form and function and ultimately has physiological consequences for the organism. Equally as important as the major cytoskeletal networks are crosslinkers which coordinate and regulate their activities. One such category of crosslinker is the spectraplakins, a family of giant, evolutionarily conserved crosslinking proteins with the rare ability to interact with each of the three major cytoskeletal networks. In particular, a mammalian spectraplakin isotype called MACF1 (microtubule actin crosslinking factor 1), also known as ACF7 (actin crosslinking factor 7), has been of particular interest in the years since its discovery; MACF1 has come under such scrutiny due to the mounting list of biological phenomena in which it has been implicated. This review is an overview of the current knowledge on the structure and function of the known spectraplakin isotypes with an emphasis on MACF1, recent studies on MACF1, and finally, an analysis of the potential of MACF1 to advance medicine. Impact statement Spectraplakins are a highly conserved group of proteins which have the rare ability to bind to each of the three major cytoskeletal networks. The mammalian spectraplakin MACF1/ACF7 has proven to be instrumental in many cellular processes (e.g. signaling and cell migration) since its identification and, as such, has been the focus of various research studies. This review is a synthesis of scientific reports on the structure, confirmed functions, and implicated roles of MACF1/ACF7 as of 2019. Based on what has been revealed thus far in terms of MACF1/ACF7’s role in complex pathologies such as metastatic cancers and inflammatory bowel disease, it appears that MACF1/ACF7 and the continued study thereof hold great potential to both enhance the design of future therapies for various diseases and vastly expand scientific understanding of organismal physiology as a whole.

Effects of Maternal Obesity and Gestational Diabetes Mellitus on the Placenta: Current Knowledge and Targets for Therapeutic Interventions

2020 ◽  
Vol 19 (2) ◽  
pp. 176-192
Author(s):  
Samantha Bedell ◽  
Janine Hutson ◽  
Barbra de Vrijer ◽  
Genevieve Eastabrook
Keyword(s):  
Diabetes Mellitus ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Maternal Obesity ◽  
Environmental Changes ◽  
Current Knowledge ◽  
Therapeutic Interventions ◽  
Placental Development ◽  
Exchange Site ◽  
And Function

: Obesity and gestational diabetes mellitus (GDM) are becoming more common among pregnant women worldwide and are individually associated with a number of placenta-mediated obstetric complications, including preeclampsia, macrosomia, intrauterine growth restriction and stillbirth. The placenta serves several functions throughout pregnancy and is the main exchange site for the transfer of nutrients and gas from mother to fetus. In pregnancies complicated by maternal obesity or GDM, the placenta is exposed to environmental changes, such as increased inflammation and oxidative stress, dyslipidemia, and altered hormone levels. These changes can affect placental development and function and lead to abnormal fetal growth and development as well as metabolic and cardiovascular abnormalities in the offspring. This review aims to summarize current knowledge on the effects of obesity and GDM on placental development and function. Understanding these processes is key in developing therapeutic interventions with the goal of mitigating these effects and preventing future cardiovascular and metabolic pathology in subsequent generations.

The Oxford Handbook of the Auditory Brainstem

2018 ◽  
Keyword(s):  
Current Knowledge ◽  
Auditory Pathway ◽  
Auditory Brainstem ◽  
Auditory Midbrain ◽  
Current State ◽  
Neuronal Mechanisms ◽  
Maladaptive Plasticity ◽  
And Function ◽  
Auditory Field

The Oxford Handbook of the Auditory Brainstem provides an in-depth reference to the organization and function of ascending and descending auditory pathways in the mammalian brainstem. Individual chapters are organized along the auditory pathway, beginning with the cochlea and ending with the auditory midbrain. Each chapter provides an introduction to the respective area and summarizes our current knowledge before discussing the disputes and challenges that the field currently faces.The handbook emphasizes the numerous forms of plasticity that are increasingly observed in many areas of the auditory brainstem. Several chapters focus on neuronal modulation of function and plasticity on the synaptic, neuronal, and circuit level, especially during development, aging, and following peripheral hearing loss. In addition, the book addresses the role of trauma-induced maladaptive plasticity with respect to its contribution in generating central hearing dysfunction, such as hyperacusis and tinnitus.The book is intended for students and postdoctoral fellows starting in the auditory field and for researchers of related fields who wish to get an authoritative and up-to-date summary of the current state of auditory brainstem research. For clinical practitioners in audiology, otolaryngology, and neurology, the book is a valuable resource of information about the neuronal mechanisms that are currently discussed as major candidates for the generation of central hearing dysfunction.

scholarly journals Identification and Functional Analysis of Apoptotic Protease Activating Factor-1 (Apaf-1) from Spodoptera litura

Insects ◽  
2021 ◽  
Vol 12 (1) ◽  
pp. 64
Author(s):  
Haihao Ma ◽  
Xiumei Yan ◽  
Lin Yan ◽  
Jingyan Zhao ◽  
Jiping Song ◽  
...  
Keyword(s):  
Spodoptera Litura ◽  
Actinomycin D ◽  
Titration Calorimetry ◽  
Apoptosis Pathway ◽  
Downstream Effector ◽  
Lepidopteran Insects ◽  
Evolutionarily Conserved ◽  
Effector Caspases ◽  
And Function

Apoptotic protease activating factor-1 (Apaf-1) is an adaptor molecule, essential for activating initiator caspase and downstream effector caspases, which directly cause apoptosis. In fruit flies, nematodes, and mammals, Apaf-1 has been extensively studied. However, the structure and function of Apaf-1 in Lepidoptera remain unclear. This study identified a novel Apaf-1 from Spodoptera litura, named Sl-Apaf-1. Sl-Apaf-1 contains three domains: a CARD domain, as well as NOD and WD motifs, and is very similar to mammalian Apaf-1. Interference of Sl-apaf-1 expression in SL-1 cells blocked apoptosis induced by actinomycin D. Overexpression of Sl-apaf-1 significantly enhances apoptosis induced by actinomycin D in Sf9/SL-1/U2OS cells, suggesting that the function of Sl-Apaf-1 is evolutionarily conserved. Furthermore, Sl-Apaf-1 could interact with Sl-caspase-5 (a homologue of mammalian caspase-9) and yielded a binding affinity of 1.37 × 106 M–1 according isothermal titration calorimetry assay. Initiator caspase (procaspase-5) of S. litura could be activated by Sl-Apaf-1 (without WD motif) in vitro, and the activated Sl-caspase-5 could cleave Sl-procaspase-1 (a homologue of caspase-3 in mammals), which directly caused apoptosis. This study demonstrates the key role of Sl-Apaf-1 in the apoptosis pathway, suggesting that the apoptosis pathway in Lepidopteran insects and mammals is conserved.

scholarly journals The Cross-Talk between Mesenchymal Stem Cells and Immune Cells in Tissue Repair and Regeneration

2021 ◽  
Vol 22 (5) ◽  
pp. 2472
Author(s):  
Carl Randall Harrell ◽  
Valentin Djonov ◽  
Vladislav Volarevic
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Immune Cells ◽  
Tissue Repair ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Multipotent Stem Cells ◽  
Tissue Repair And Regeneration ◽  
Almost All ◽  
And Function

Mesenchymal stem cells (MSCs) are self-renewable, rapidly proliferating, multipotent stem cells which reside in almost all post-natal tissues. MSCs possess potent immunoregulatory properties and, in juxtacrine and paracrine manner, modulate phenotype and function of all immune cells that participate in tissue repair and regeneration. Additionally, MSCs produce various pro-angiogenic factors and promote neo-vascularization in healing tissues, contributing to their enhanced repair and regeneration. In this review article, we summarized current knowledge about molecular mechanisms that regulate the crosstalk between MSCs and immune cells in tissue repair and regeneration.

scholarly journals Antioxidant and Signaling Role of Plastid-Derived Isoprenoid Quinones and Chromanols

2021 ◽  
Vol 22 (6) ◽  
pp. 2950
Author(s):  
Beatrycze Nowicka ◽  
Agnieszka Trela-Makowej ◽  
Dariusz Latowski ◽  
Kazimierz Strzalka ◽  
Renata Szymańska
Keyword(s):  
Current Knowledge ◽  
Stress Factors ◽  
Oxygenic Photosynthesis ◽  
Ros Generation ◽  
Main Site ◽  
Storage Lipids ◽  
Abiotic Stress Factors ◽  
Cell Components ◽  
And Function

Plant prenyllipids, especially isoprenoid chromanols and quinols, are very efficient low-molecular-weight lipophilic antioxidants, protecting membranes and storage lipids from reactive oxygen species (ROS). ROS are byproducts of aerobic metabolism that can damage cell components, they are also known to play a role in signaling. Plants are particularly prone to oxidative damage because oxygenic photosynthesis results in O2 formation in their green tissues. In addition, the photosynthetic electron transfer chain is an important source of ROS. Therefore, chloroplasts are the main site of ROS generation in plant cells during the light reactions of photosynthesis, and plastidic antioxidants are crucial to prevent oxidative stress, which occurs when plants are exposed to various types of stress factors, both biotic and abiotic. The increase in antioxidant content during stress acclimation is a common phenomenon. In the present review, we describe the mechanisms of ROS (singlet oxygen, superoxide, hydrogen peroxide and hydroxyl radical) production in chloroplasts in general and during exposure to abiotic stress factors, such as high light, low temperature, drought and salinity. We highlight the dual role of their presence: negative (i.e., lipid peroxidation, pigment and protein oxidation) and positive (i.e., contribution in redox-based physiological processes). Then we provide a summary of current knowledge concerning plastidic prenyllipid antioxidants belonging to isoprenoid chromanols and quinols, as well as their structure, occurrence, biosynthesis and function both in ROS detoxification and signaling.

scholarly journals Neurons interact with the microbiome: an evolutionary-informed perspective

Neuroforum ◽  
2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Christoph Giez ◽  
Alexander Klimovich ◽  
Thomas C. G. Bosch
Keyword(s):  
Nervous System ◽  
Neural Circuits ◽  
Current Knowledge ◽  
System Development ◽  
Nervous System Development ◽  
Comprehensive Understanding ◽  
Strategic Model ◽  
Microbe Interactions ◽  
Host Microbe Interactions ◽  
And Function

Abstract Animals have evolved within the framework of microbes and are constantly exposed to diverse microbiota. Microbes colonize most, if not all, animal epithelia and influence the activity of many organs, including the nervous system. Therefore, any consideration on nervous system development and function in the absence of the recognition of microbes will be incomplete. Here, we review the current knowledge on the nervous systems of Hydra and its role in the host–microbiome communication. We show that recent advances in molecular and imaging methods are allowing a comprehensive understanding of the capacity of such a seemingly simple nervous system in the context of the metaorganism. We propose that the development, function and evolution of neural circuits must be considered in the context of host–microbe interactions and present Hydra as a strategic model system with great basic and translational relevance for neuroscience.

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