Loss of the extraproteasomal ubiquitin receptor Rings lost impairs ring canal growth in Drosophila oogenesis

In Drosophila melanogaster oogenesis, there are 16 germline cells that form a cyst and stay connected to each other by ring canals. Ring canals allow the cytoplasmic transport of proteins, messenger ribonucleic acids, and yolk components from the nurse cells into the oocyte. In this paper, we describe the protein Rings lost (Rngo) and show that it is required for ring canal growth in germline cysts. rngo is an essential gene, and germline clones of a rngo-null allele show defects in ovary development, including mislocalization of ring canal proteins and fusion of germline cells. Rngo appears to be a ubiquitin receptor that possesses a ubiquitin-like domain, a ubiquitin-associated domain, and a retroviral-like aspartate protease (RVP) domain. Rngo binds to ubiquitin and to the 26S proteasome and colocalizes with both in germline cells, and its RVP domain is required for dimerization of Rngo and for its function in vivo. Our results thus show, for the first time, a function for a ubiquitin receptor in Drosophila development.

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Nessun Dorma, a novel centralspindlin partner, is required for cytokinesis in Drosophila spermatocytes

The Journal of Cell Biology ◽

10.1083/jcb.201007060 ◽

2010 ◽

Vol 191 (7) ◽

pp. 1351-1365 ◽

Cited By ~ 17

Author(s):

Emilie Montembault ◽

Wei Zhang ◽

Marcin R. Przewloka ◽

Vincent Archambault ◽

Emeric W. Sevin ◽

...

Keyword(s):

Essential Gene ◽

Male Meiosis ◽

Carbohydrate Binding ◽

Ring Canal ◽

Daughter Cells ◽

High Affinity ◽

Evolutionarily Conserved ◽

Ring Canals ◽

Female Germline

Cytokinesis, the final step of cell division, usually ends with the abscission of the two daughter cells. In some tissues, however, daughter cells never completely separate and remain interconnected by intercellular bridges or ring canals. In this paper, we report the identification and analysis of a novel ring canal component, Nessun Dorma (Nesd), isolated as an evolutionarily conserved partner of the centralspindlin complex, a key regulator of cytokinesis. Nesd contains a pectin lyase–like domain found in proteins that bind to polysaccharides, and we present evidence that it has high affinity for β-galactosides in vitro. Moreover, nesd is an essential gene in Drosophila melanogaster, in which it is required for completion of cytokinesis during male meiosis and possibly in female germline cells. Our findings indicate that Nesd is a novel carbohydrate-binding protein that functions together with centralspindlin in late cytokinesis, thus highlighting the importance of glycosylation in this process.

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An A-kinase anchoring protein is required for Protein kinase A regulatory subunit localization and morphology of actin structures during oogenesis inDrosophila

Development ◽

10.1242/dev.129.19.4423 ◽

2002 ◽

Vol 129 (19) ◽

pp. 4423-4433 ◽

Cited By ~ 1

Author(s):

Stephen M. Jackson ◽

Celeste A. Berg

Keyword(s):

Protein Kinase ◽

Protein Kinase A ◽

Membrane Integrity ◽

Regulatory Subunit ◽

Small Ring ◽

Nurse Cells ◽

Ring Canal ◽

Ring Canals ◽

Germline Cells ◽

Kinase A

Protein kinase A (PKA) holoenzyme is anchored to specific subcellular regions by interactions between regulatory subunits (Pka-R) and A-kinase anchoring proteins (AKAPs). We examine the functional importance of PKA anchoring during Drosophila oogenesis by analyzing membrane integrity and actin structures in mutants with disruptions in Akap200, an AKAP. In wild-type ovaries, Pka-RII and Akap200 localized to membranes and to the outer rim of ring canals, actin-rich structures that connect germline cells. In Akap200 mutant ovaries, Pka-RII membrane localization decreased, leading to a destabilization of membrane structures and the formation of binucleate nurse cells. Defects in membrane integrity could be mimicked by expressing a constitutively active PKA catalytic subunit (Pka-C) throughout germline cells. Unexpectedly, nurse cells in Akap200 mutant ovaries also had enlarged, thin ring canals. In contrast, overexpressing Akap200 in the germline resulted in thicker, smaller ring canals. To investigate the role of Akap200 in regulating ring canal growth, we examined genetic interactions with other genes that are known to regulate ring canal morphology. Akap200 mutations suppressed the small ring canal phenotype produced by Src64B mutants, linking Akap200 with the non-receptor tyrosine kinase pathway. Together, these results provide the first evidence that PKA localization is required for morphogenesis of actin structures in an intact organism.

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A subset of dynamic actin rearrangements in Drosophila requires the Arp2/3 complex

The Journal of Cell Biology ◽

10.1083/jcb.200109065 ◽

2002 ◽

Vol 156 (4) ◽

pp. 677-687 ◽

Cited By ~ 107

Author(s):

Andrew M. Hudson ◽

Lynn Cooley

Keyword(s):

Actin Filaments ◽

Nurse Cell ◽

Loss Of Function ◽

Ring Canal ◽

Cell Cytoplasm ◽

Ring Canals ◽

Genes Encoding ◽

Related Proteins

The Arp2/3 complex has been shown to dramatically increase the slow spontaneous rate of actin filament nucleation in vitro, and it is known to be important for remodeling the actin cytoskeleton in vivo. We isolated and characterized loss of function mutations in genes encoding two subunits of the Drosophila Arp2/3 complex: Arpc1, which encodes the homologue of the p40 subunit, and Arp3, encoding one of the two actin-related proteins. We used these mutations to study how the Arp2/3 complex contributes to well-characterized actin structures in the ovary and the pupal epithelium. We found that the Arp2/3 complex is required for ring canal expansion during oogenesis but not for the formation of parallel actin bundles in nurse cell cytoplasm and bristle shaft cells. The requirement for Arp2/3 in ring canals indicates that the polymerization of actin filaments at the ring canal plasma membrane is important for driving ring canal growth.

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Hexapod Assassins’ Potion: Venom Composition and Bioactivity from the Eurasian Assassin Bug Rhynocoris iracundus

Biomedicines ◽

10.3390/biomedicines9070819 ◽

2021 ◽

Vol 9 (7) ◽

pp. 819

Author(s):

Nicolai Rügen ◽

Timothy P. Jenkins ◽

Natalie Wielsch ◽

Heiko Vogel ◽

Benjamin-Florian Hempel ◽

...

Keyword(s):

Biomedical Applications ◽

Galleria Mellonella ◽

Systemic Reactions ◽

Venom Composition ◽

Assassin Bug ◽

Molecular Components ◽

First Time ◽

Tissue Digestion

Assassin bug venoms are potent and exert diverse biological functions, making them potential biomedical goldmines. Besides feeding functions on arthropods, assassin bugs also use their venom for defense purposes causing localized and systemic reactions in vertebrates. However, assassin bug venoms remain poorly characterized. We collected the venom from the assassin bug Rhynocoris iracundus and investigated its composition and bioactivity in vitro and in vivo. It caused lysis of murine neuroblastoma, hepatoma cells, and healthy murine myoblasts. We demonstrated, for the first time, that assassin bug venom induces neurolysis and suggest that it counteracts paralysis locally via the destruction of neural networks, contributing to tissue digestion. Furthermore, the venom caused paralysis and melanization of Galleria mellonella larvae and pupae, whilst also possessing specific antibacterial activity against Escherichia coli, but not Listeria grayi and Pseudomonas aeruginosa. A combinatorial proteo-transcriptomic approach was performed to identify potential toxins responsible for the observed effects. We identified neurotoxic Ptu1, an inhibitory cystin knot (ICK) toxin homologous to ω-conotoxins from cone snails, cytolytic redulysins homologous to trialysins from hematophagous kissing bugs, and pore-forming hemolysins. Additionally, chitinases and kininogens were found and may be responsible for insecticidal and cytolytic activities. We demonstrate the multifunctionality and complexity of assassin bug venom, which renders its molecular components interesting for potential biomedical applications.

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Carbon dots derived from Fusobacterium nucleatum for intracellular determination of Fe3+ and bioimaging both in vitro and in vivo

Analytical Methods ◽

10.1039/d1ay00020a ◽

2021 ◽

Author(s):

Lijuan Liu ◽

Shengting Zhang ◽

Xiaodan Zheng ◽

Hongmei Li ◽

Qi Chen ◽

...

Keyword(s):

Carbon Dots ◽

Fusobacterium Nucleatum ◽

Living Cells ◽

First Time ◽

Fluorescent Carbon Dots ◽

Fluorescent Carbon

Fusobacterium nucleatum has been employed for the first time to synthesize fluorescent carbon dots which could be applied for the determination of Fe3+ ions in living cells and bioimaging in vitro and in vivo with excellent biocompatibility.

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Anti-Tumor and Anti-Inflammatory Activity In Vivo of Apodanthera congestiflora Cogn. (Cucurbitaceae)

Pharmaceutics ◽

10.3390/pharmaceutics13050743 ◽

2021 ◽

Vol 13 (5) ◽

pp. 743

Author(s):

Geovana F. G. Silvestre ◽

Renally P. Lucena ◽

Genil D. Oliveira ◽

Helimarcos N. Pereira ◽

Jhonatta A. B. Dias ◽

...

Keyword(s):

Inflammatory Activity ◽

Phytochemical Investigation ◽

Significant Toxicity ◽

Biological Tests ◽

Ehrlich's Carcinoma ◽

Anti Inflammatory ◽

Pharmacological Potential ◽

First Time ◽

Anti Tumor Activity

This work aimed to carry out a study of Apodanthera congestiflora by investigating its chemical composition and pharmacological potential. From the dichloromethane phase (Dic-Ac) of the A. congestiflora stems, three compounds were identified: cayaponoside C5b (Ac-1), cabenoside C (Ac-2) and fevicordin C2 glucoside (Ac-3), being last identified for the first time as a natural product. These compounds were obtained by chromatographic methods and their structures were elucidated by means of spectroscopic analysis of IR, MS and NMR. In the quantification of Dic-Ac, it was possible to observe the presence of 7% of cayaponoside C5b. Dic-Ac showed significant toxicity for in vivo tests, with macroscopic and biochemical changes. The anti-inflammatory activity of Dic-Ac was investigated using the paw edema model. A decrease in inflammatory signs was observed in the first 5 h and the most effective dose in reducing edema with was 7.5 mg kg−1 (66.6%). Anti-tumor activity of Dic-Ac was evaluated by Ehrlich’s carcinoma model, which showed inhibition rate of 78.46% at 15 mg kg−1 dosage. The phytochemical investigation, together with the biological tests carried out in this study, demonstrated that A. congestiflora is a promising species in the search for therapeutics, since it contains substances with high pharmacological potential in its composition.

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The antimicrobial potential of cannabidiol

Communications Biology ◽

10.1038/s42003-020-01530-y ◽

2021 ◽

Vol 4 (1) ◽

Author(s):

Mark A. T. Blaskovich ◽

Angela M. Kavanagh ◽

Alysha G. Elliott ◽

Bing Zhang ◽

Soumya Ramu ◽

...

Keyword(s):

Bacterial Infections ◽

Modern Medicine ◽

Gram Negative Bacteria ◽

Gram Negative ◽

New Class ◽

Clostridioides Difficile ◽

Excellent Activity ◽

Induce Resistance ◽

First Time

AbstractAntimicrobial resistance threatens the viability of modern medicine, which is largely dependent on the successful prevention and treatment of bacterial infections. Unfortunately, there are few new therapeutics in the clinical pipeline, particularly for Gram-negative bacteria. We now present a detailed evaluation of the antimicrobial activity of cannabidiol, the main non-psychoactive component of cannabis. We confirm previous reports of Gram-positive activity and expand the breadth of pathogens tested, including highly resistant Staphylococcus aureus, Streptococcus pneumoniae, and Clostridioides difficile. Our results demonstrate that cannabidiol has excellent activity against biofilms, little propensity to induce resistance, and topical in vivo efficacy. Multiple mode-of-action studies point to membrane disruption as cannabidiol’s primary mechanism. More importantly, we now report for the first time that cannabidiol can selectively kill a subset of Gram-negative bacteria that includes the ‘urgent threat’ pathogen Neisseria gonorrhoeae. Structure-activity relationship studies demonstrate the potential to advance cannabidiol analogs as a much-needed new class of antibiotics.

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Autophagy Deficiency by Atg4B Loss Leads to Metabolomic Alterations in Mice

Metabolites ◽

10.3390/metabo11080481 ◽

2021 ◽

Vol 11 (8) ◽

pp. 481

Author(s):

Gemma G. Martínez-García ◽

Raúl F. Pérez ◽

Álvaro F. Fernández ◽

Sylvere Durand ◽

Guido Kroemer ◽

...

Keyword(s):

Skeletal Muscle ◽

Amino Acids ◽

Mammalian Cells ◽

Tissue Homeostasis ◽

In Vivo Studies ◽

Protective Mechanism ◽

Cardiac Damage ◽

Wide Range ◽

First Time

Autophagy is an essential protective mechanism that allows mammalian cells to cope with a variety of stressors and contributes to maintaining cellular and tissue homeostasis. Due to these crucial roles and also to the fact that autophagy malfunction has been described in a wide range of pathologies, an increasing number of in vivo studies involving animal models targeting autophagy genes have been developed. In mammals, total autophagy inactivation is lethal, and constitutive knockout models lacking effectors of this route are not viable, which has hindered so far the analysis of the consequences of a systemic autophagy decline. Here, we take advantage of atg4b−/− mice, an autophagy-deficient model with only partial disruption of the process, to assess the effects of systemic reduction of autophagy on the metabolome. We describe for the first time the metabolic footprint of systemic autophagy decline, showing that impaired autophagy results in highly tissue-dependent alterations that are more accentuated in the skeletal muscle and plasma. These changes, which include changes in the levels of amino-acids, lipids, or nucleosides, sometimes resemble those that are frequently described in conditions like aging, obesity, or cardiac damage. We also discuss different hypotheses on how impaired autophagy may affect the metabolism of several tissues in mammals.

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Electro-Quasistatic Animal Body Communication for Untethered Rodent Biopotential Recording

Scientific Reports ◽

10.1038/s41598-021-81108-8 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Shreeya Sriram ◽

Shitij Avlani ◽

Matthew P. Ward ◽

Shreyas Sen

Keyword(s):

Lower Energy ◽

Sensor Node ◽

State Of The Art ◽

The Body ◽

Animal Body ◽

Current State ◽

Communication Modalities ◽

First Time ◽

Biopotential Recording

AbstractContinuous multi-channel monitoring of biopotential signals is vital in understanding the body as a whole, facilitating accurate models and predictions in neural research. The current state of the art in wireless technologies for untethered biopotential recordings rely on radiative electromagnetic (EM) fields. In such transmissions, only a small fraction of this energy is received since the EM fields are widely radiated resulting in lossy inefficient systems. Using the body as a communication medium (similar to a ’wire’) allows for the containment of the energy within the body, yielding order(s) of magnitude lower energy than radiative EM communication. In this work, we introduce Animal Body Communication (ABC), which utilizes the concept of using the body as a medium into the domain of untethered animal biopotential recording. This work, for the first time, develops the theory and models for animal body communication circuitry and channel loss. Using this theoretical model, a sub-inch$$^3$$ 3 [1″ × 1″ × 0.4″], custom-designed sensor node is built using off the shelf components which is capable of sensing and transmitting biopotential signals, through the body of the rat at significantly lower powers compared to traditional wireless transmissions. In-vivo experimental analysis proves that ABC successfully transmits acquired electrocardiogram (EKG) signals through the body with correlation $$>99\%$$ > 99 % when compared to traditional wireless communication modalities, with a 50$$\times$$ × reduction in power consumption.

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Fe3O4@Pt nanoparticles to enable combinational electrodynamic/chemodynamic therapy

Journal of Nanobiotechnology ◽

10.1186/s12951-021-00957-7 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Tong Chen ◽

Qiang Chu ◽

Mengyang Li ◽

Gaorong Han ◽

Xiang Li

Keyword(s):

Fenton Reaction ◽

Pt Nanoparticles ◽

Therapeutic Modality ◽

Ros Generation ◽

Tumor Treatment ◽

Superior Efficacy ◽

Platinum Nanocrystals ◽

First Time

AbstractElectrodynamic therapy (EDT) has recently emerged as a potential external field responsive approach for tumor treatment. While it presents a number of clear superiorities, EDT inherits the intrinsic challenges of current reactive oxygen species (ROS) based therapeutic treatments owing to the complex tumor microenvironment, including glutathione (GSH) overexpression, acidity and others. Herein for the first time, iron oxide nanoparticles are decorated using platinum nanocrystals (Fe3O4@Pt NPs) to integrate the current EDT with chemodynamic phenomenon and GSH depletion. Fe3O4@Pt NPs can effectively induce ROS generation based on the catalytic reaction on the surface of Pt nanoparticles triggered by electric field (E), and meanwhile it may catalyze intracellular H2O2 into ROS via Fenton reaction. In addition, Fe3+ ions released from Fe3O4@Pt NPs under the acidic condition in tumor cells consume GSH in a rapid fashion, inhibiting ROS clearance to enhance its antitumor efficacy. As a result, considerable in vitro and in vivo tumor inhibition phenomena are observed. This study has demonstrated an alternative concept of combinational therapeutic modality with superior efficacy.

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