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Silencing of the proteasome and oxidative stress impair endoplasmic reticulum targeting and signal cleavage of a prostate carcinoma antigen.

Biochem Biophys Res Commun 2021 Mar 25;554:56-62. Epub 2021 Mar 25.

Division of Immunology, Department of Biology, University of Konstanz, Konstanz, Germany; Biotechnology Institute Thurgau at the University of Konstanz, Kreuzlingen, Switzerland. Electronic address:

The endoplasmic reticulum (ER) is an organelle with high protein density and therefore prone to be damaged by protein aggregates. One proposed preventive measure is a pre-emptive quality control pathway that attenuates ER import during protein folding stress. ER resident proteins are targeted into the ER via signal peptides cleaved rapidly upon ER insertion by the ER signal peptidase. Read More

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A nuclear factor-kappa B inhibiting peptide suppresses innate immune receptors and gliosis in a transgenic mouse model of Alzheimer's disease.

Biomed Pharmacother 2021 Mar 20;138:111405. Epub 2021 Mar 20.

Department of Oral Pathology, Medicine and Radiology, Indiana University School of Dentistry, United States; Provaidya LLC, Indianapolis, IN, United States. Electronic address:

A disproportionate increase in activated nuclear factor-kappa B (NF-κB) has been shown to drive the Aβ deposition, neuroinflammation and neurodegeneration in Alzheimer's disease (AD). Hence, selective targeting of activated p65 represents an attractive therapeutic approach for AD. Glucocorticoid induced leucine zipper (GILZ) is a NF-κB interactant that binds and sequesters the activated p65 in the cytoplasm. Read More

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Cholesterol and cholesterol bilayer domains inhibit binding of alpha-crystallin to the membranes made of the major phospholipids of eye lens fiber cell plasma membranes.

Exp Eye Res 2021 Mar 17;206:108544. Epub 2021 Mar 17.

Department of Physics, Boise State University, Boise, ID, 83725, USA; Biomolecular Sciences Graduate Program, Boise State University, Boise, ID, 83725, USA. Electronic address:

The concentration of α-crystallin decreases in the eye lens cytoplasm, with a corresponding increase in membrane-bound α-crystallin during cataract formation. The eye lens's fiber cell plasma membrane consists of extremely high cholesterol (Chol) content, forming cholesterol bilayer domains (CBDs) within the membrane. The role of high Chol content in the lens membrane is unclear. Read More

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Optimality in Self-Organized Molecular Sorting.

Phys Rev Lett 2021 Feb;126(8):088101

Institute of Condensed Matter Physics and Complex Systems, Department of Applied Science and Technology, Politecnico di Torino, Corso Duca degli Abruzzi 24, 10129 Torino, Italy.

We introduce a simple physical picture to explain the process of molecular sorting, whereby specific proteins are concentrated and distilled into submicrometric lipid vesicles in eukaryotic cells. To this purpose, we formulate a model based on the coupling of spontaneous molecular aggregation with vesicle nucleation. Its implications are studied by means of a phenomenological theory describing the diffusion of molecules toward multiple sorting centers that grow due to molecule absorption and are extracted when they reach a sufficiently large size. Read More

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February 2021

Aptamer Functionalized Upconversion Nanotheranostic Agent With Nuclear Targeting as the Highly Localized Drug-Delivery System of Doxorubicin.

Front Bioeng Biotechnol 2021 22;9:639487. Epub 2021 Feb 22.

Shandong Provincial Key Laboratory of Detection Technology for Tumor Markers, College of Chemistry and Chemical Engineering, Linyi University, Shandong, China.

As a widely used anticancer drug, doxorubicin (DOX) could induce cell death mainly interfering with DNA activity; thus, DOX could perform therapeutic effects mainly in the cell nucleus. However, most of the reported drug delivery systems lacked the well localization in the nucleus and released DOX molecules into the cytoplasm. Due to formidable barriers formed in the nuclear envelope, only around 1% of DOX could reach the nucleus and keep active. Read More

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February 2021

Mixed signals - how exploits host-cell communication and signaling to establish infection.

J Cell Sci 2021 Mar 10;134(5). Epub 2021 Mar 10.

Departamento de Genética, Ecologia e Evolução, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, 486, Brazil

Chagas disease (American trypanosomiasis) is a 'neglected' pathology that affects millions of people worldwide, mainly in Latin America. , the causative agent, is an obligate intracellular parasite with a complex and diverse biology that infects several mammalian species, including humans. Because of genetic variability among strains and the presence of four biochemically and morphologically distinct parasite forms, the outcome of infection varies considerably depending on host cell type and parasite strain. Read More

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[Research advances on mechanism of exosomes derived from adipose derived stem cells in the treatment of chronic wounds].

Zhonghua Shao Shang Za Zhi 2021 Feb;37(2):191-195

Department of Burns and Plastic Surgery of Subei People's Hospital, Clinical Medical College of Yangzhou University, Yangzhou 225001, China.

Exosomes are a kind of membrane vesicle with a diameter of 30-150 nm. It is formed by the budding of multiple vesicles in cells, which can fuse with the cell membrane and be released into the extracellular matrix. Adipose derived stem cells (ADSCs) have the potential of self-renewal and multi-directional differentiation. Read More

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February 2021

Alohomora! What the entry mechanisms tell us about the evolution and diversification of giant viruses and their hosts.

Curr Opin Virol 2021 Feb 26;47:79-85. Epub 2021 Feb 26.

Laboratório de Vírus, Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, Belo Horizonte, 31270-901, Brasil. Electronic address:

The virosphere is fascinatingly vast and diverse, but as mandatory intracellular parasites, viral particles must reach the intracellular space to guarantee their species' permanence on the planet. While most known viruses that infect animals explore the endocytic pathway to enter the host cell, a diverse group of ancient viruses that make up the phylum Nucleocytoviricota appear to have evolved to explore new access' routes to the cell's cytoplasm. Giant viruses of amoeba take advantage of the phagocytosis process that these organisms exploit a lot, while phycodnavirus must actively break through a algal cellulose cell wall. Read More

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February 2021

Computational Resources and Strategies to Construct Single-Molecule Models of FISH.

Methods Mol Biol 2021 ;2246:317-330

Escuela Superior de Ingeniería Informática (ESEI), University of Vigo, Ourense, Spain.

Currently, the interactions occurring between oligonucleotides and the cellular envelope of bacteria are not fully resolved at the molecular level. Understanding these interactions is essential to gain insights on how to improve the internalization of the tagged oligonucleotides during fluorescence in situ hybridization (FISH). Agent-based modeling (ABM) is a promising in silico tool to dynamically simulate FISH and bring forward new knowledge on this process. Read More

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Delivery of Oligonucleotides into Bacteria by Fusogenic Liposomes.

Methods Mol Biol 2021 ;2246:87-96

LEPABE - Laboratory for Process Engineering, Environment, Biotechnology and Energy, Department of Chemical Engineering, Faculty of Engineering, University of Porto, Porto, Portugal.

Oligonucleotides able to hybridize bacterial RNA via in situ hybridization may potentially act as new antimicrobials, replacing antibiotics, and as fast in vivo diagnostic probes, outperforming current clinical methodologies. Nonetheless, oligonucleotides are not able to efficiently permeate the multi-layered bacterial envelope to reach their target RNA in the cytosol. Cationic fusogenic liposomes are here suggested as vehicles to enable the internalization of oligonucleotides in bacteria. Read More

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Cytoplasmic Trafficking of Nanoparticles Delivers Plasmid DNA for Macrophage Gene-Editing.

Curr Gene Ther 2021 Feb 10. Epub 2021 Feb 10.

Department of Molecular and Translational Medicine, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center at El Paso, 5001 El Paso Drive, El Paso, Texas 79905-2827. United States.

Background: Successful nanoparticle delivery of gene-editing tools is dependent on the ability of nanoparticles to pass through the cellular membrane, move through the cytoplasm, and cross the nuclear envelope to enter the nucleus. It is critical that intracellular nanoparticles interact with the cytoskeletal network to move toward the nucleus and must escape degradation pathways including lysosomal digestion. Without efficient intracellular trafficking, nanoparticles loaded with gene editing tools cannot reach the nucleus for efficient transfection. Read More

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February 2021

Field Sanitation and Foliar Application of PMS-702 for the Control of Rice Sheath Blight.

Plant Pathol J 2021 Feb;37(1):57-71

Department of Plant Pathology, National Chung Hsing University, Taichung 40227, Taiwan.

Rice sheath blight (ShB), caused by Kühn AG1-IA, is one of the destructive rice diseases worldwide. The aims of this study were to develop biocontrol strategies focusing on field sanitation and foliar application with a biocontrol agent for ShB management. PMS-702 showed a great antagonistic activity against . Read More

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February 2021

Functional expression and localisation of HOPS/TMUB1 in mouse lens.

Biosci Rep 2021 Feb;41(2)

Department of Medicine and Surgery, Piazzale L. Severi 1, University of Perugia, Perugia, Italy.

Transparency represents the functional phenotype of eye lens. A number of defined steps including quiescence, proliferation, migration and cell differentiation culminates in cell elongation and organelle degradation, allowing the light to reach the retina. HOPS (Hepatocyte Odd Protein Shuttling)/TMUB1 (Trans Membrane Ubiquitin-like containing protein 1) is a nucleo-cytoplasmic shuttling protein, highly expressed both in vivo and in vitro proliferating systems, bearing a ubiquitin-like domain. Read More

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February 2021

Modification of magnetic molybdenum disulfide by chitosan/carboxymethylcellulose with enhanced dispersibility for targeted photothermal-/chemotherapy of cancer.

J Mater Chem B 2021 02;9(7):1833-1845

School of Pharmacy, Jiangsu University, 212013, China.

In this work, magnetic molybdenum disulfide (mMoS2) was synthesized firstly. Then, layer-by-layer (LbL) self-assembly technology was used for the preparation of chitosan/carboxymethylcellulose functionalized mMoS2 nanocomposites. The nanocomposites with the diameter of 0. Read More

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February 2021

Clearing Traffic Jams During Protein Translocation Across Membranes.

Front Cell Dev Biol 2020 8;8:610689. Epub 2021 Jan 8.

Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, United States.

Protein translocation across membranes is a critical facet of protein biogenesis in compartmentalized cells as proteins synthesized in the cytoplasm often need to traverse across lipid bilayers proteinaceous channels to reach their final destinations. It is well established that protein biogenesis is tightly linked to various protein quality control processes, which monitor errors in protein folding, modification, and localization. However, little is known about how cells cope with translocation defective polypeptides that clog translocation channels (translocons) during protein translocation. Read More

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January 2021

Compartmentation of β -adrenoceptor stimulated cAMP responses by phosphodiesterase types 2 and 3 in cardiac ventricular myocytes.

Br J Pharmacol 2021 Apr 20;178(7):1574-1587. Epub 2021 Feb 20.

Department of Pharmacology, University of Nevada, Reno, Nevada, USA.

Background And Purpose: In cardiac myocytes, cyclic AMP (cAMP) produced by both β - and β -adrenoceptors increases L-type Ca channel activity and myocyte contraction. However, only cAMP produced by β -adrenoceptors enhances myocyte relaxation through phospholamban-dependent regulation of the sarco/endoplasmic reticulum Ca ATPase 2 (SERCA2). Here we have tested the hypothesis that stimulation of β -adrenoceptors produces a cAMP signal that is unable to reach SERCA2 and determine what role, if any, phosphodiesterase (PDE) activity plays in this compartmentation. Read More

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Multivalent dextran hybrids for efficient cytosolic delivery of biomolecular cargoes.

J Pept Sci 2021 Apr 17;27(4):e3298. Epub 2021 Jan 17.

Institute for Organic Chemistry and Biochemistry, Technical University of Darmstadt, Alarich-Weiss-Straße 4, Darmstadt, 64287, Germany.

The development of novel biotherapeutics based on peptides and proteins is often limited to extracellular targets, because these molecules are not able to reach the cytosol. In recent years, several approaches were proposed to overcome this limitation. A plethora of cell-penetrating peptides (CPPs) was developed for cytoplasmic delivery of cell-impermeable cargo molecules. Read More

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Regulation of glial size by eicosapentaenoic acid through a novel Golgi apparatus mechanism.

PLoS Biol 2020 12 28;18(12):e3001051. Epub 2020 Dec 28.

Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina, United States of America.

Coordination of cell growth is essential for the development of the brain, but the molecular mechanisms underlying the regulation of glial and neuronal size are poorly understood. To investigate the mechanisms involved in glial size regulation, we used Caenorhabditis elegans amphid sheath (AMsh) glia as a model and show that a conserved cis-Golgi membrane protein eas-1/GOLT1B negatively regulates glial growth. We found that eas-1 inhibits a conserved E3 ubiquitin ligase rnf-145/RNF145, which, in turn, promotes nuclear activation of sbp-1/ SREBP, a key regulator of sterol and fatty acid synthesis, to restrict cell growth. Read More

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December 2020

Unconventional Secretion of Nigerolysins A from Species.

Microorganisms 2020 Dec 11;8(12). Epub 2020 Dec 11.

National Institute of Chemistry, SI-1000 Ljubljana, Slovenia.

Aegerolysins are small lipid-binding proteins particularly abundant in fungi. Aegerolysins from oyster mushrooms interact with an insect-specific membrane lipid and, together with MACPF proteins produced by the same organism, form pesticidal pore-forming complexes. The specific interaction with the same membrane lipid was recently demonstrated for nigerolysin A2 (NigA2), an aegerolysin from . Read More

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December 2020

Myonuclear content regulates cell size with similar scaling properties in mice and humans.

Nat Commun 2020 12 8;11(1):6288. Epub 2020 Dec 8.

Department of Biosciences, University of Oslo, Oslo, Norway.

Muscle fibers are the largest cells in the body, and one of its few syncytia. Individual cell sizes are variable and adaptable, but what governs cell size has been unclear. We find that muscle fibers are DNA scarce compared to other cells, and that the nuclear number (N) adheres to the relationship N = aV where V is the cytoplasmic volume. Read More

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December 2020

Structure and Biomechanics during Xylem Vessel Transdifferentiation in .

Plants (Basel) 2020 Dec 5;9(12). Epub 2020 Dec 5.

Division of Engineering and Applied Science, California Institute of Technology, Pasadena, CA 91125, USA.

Individual plant cells are the building blocks for all plantae and artificially constructed plant biomaterials, like biocomposites. Secondary cell walls (SCWs) are a key component for mediating mechanical strength and stiffness in both living vascular plants and biocomposite materials. In this paper, we study the structure and biomechanics of cultured plant cells during the cellular developmental stages associated with SCW formation. Read More

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December 2020

Cattle mitogenome variation reveals a post-glacial expansion of haplogroup P and an early incorporation into northeast Asian domestic herds.

Sci Rep 2020 11 30;10(1):20842. Epub 2020 Nov 30.

Dipartimento di Biologia e Biotecnologie "L. Spallanzani", Università di Pavia, Pavia, Italy.

Surveys of mitochondrial DNA (mtDNA) variation have shown that worldwide domestic cattle are characterized by just a few major haplogroups. Two, T and I, are common and characterize Bos taurus and Bos indicus, respectively, while the other three, P, Q and R, are rare and are found only in taurine breeds. Haplogroup P is typical of extinct European aurochs, while intriguingly modern P mtDNAs have only been found in northeast Asian cattle. Read More

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November 2020

Portfolio Targeting Strategy To Realize the Assembly and Membrane Fusion-Mediated Delivery of Gold Nanoparticles to Mitochondria for Enhanced NIR Photothermal Therapies.

Bioconjug Chem 2020 12 23;31(12):2719-2725. Epub 2020 Nov 23.

Translational Medical Center for Stem Cell Therapy & Institute for Regenerative Medicine, Shanghai East Hospital, Tongji University School of Medicine, 1800 Yuntai Road, Shanghai, 200123, China.

Targeting mitochondria has always been a challenging goal for therapeutic nanoparticle agents due to their heterotypic features and size, which usually lead to a lysosome/endosome endocytosis pathway. To overcome this limitation, in this work, a portfolio targeting strategy combining a small targeting molecule with a biomembrane was developed. Modification of small targeting molecule HN-TPP on gold nanoparticles (GNPs) could not only facilitate the mitochondrial targeting but could also induce gold nanoparticle assembly. Read More

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December 2020

Concerted action of kinesins KIF5B and KIF13B promotes efficient secretory vesicle transport to microtubule plus ends.

Elife 2020 11 11;9. Epub 2020 Nov 11.

Cell Biology, Neurobiology and Biophysics, Department of Biology, Faculty of Science, Utrecht University, Utrecht, Netherlands.

Intracellular transport relies on multiple kinesins, but it is poorly understood which kinesins are present on particular cargos, what their contributions are and whether they act simultaneously on the same cargo. Here, we show that Rab6-positive secretory vesicles are transported from the Golgi apparatus to the cell periphery by kinesin-1 KIF5B and kinesin-3 KIF13B, which determine the location of secretion events. KIF5B plays a dominant role, whereas KIF13B helps Rab6 vesicles to reach freshly polymerized microtubule ends, to which KIF5B binds poorly, likely because its cofactors, MAP7-family proteins, are slow in populating these ends. Read More

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November 2020

ER functions are exploited by viruses to support distinct stages of their life cycle.

Biochem Soc Trans 2020 10;48(5):2173-2184

Department of Cell and Developmental Biology, University of Michigan Medical School, 109 Zina Pitcher Place, BSRB 3043, Ann Arbor, MI 48109, USA.

The endoplasmic reticulum (ER), with its expansive membranous system and a vast network of chaperones, enzymes, sensors, and ion channels, orchestrates diverse cellular functions, ranging from protein synthesis, folding, secretion, and degradation to lipid biogenesis and calcium homeostasis. Strikingly, some of the functions of the ER are exploited by viruses to promote their life cycles. During entry, viruses must penetrate a host membrane and reach an intracellular destination to express and replicate their genomes. Read More

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October 2020

Targeting c-Myc with a novel Peptide Nuclear Delivery Device.

Sci Rep 2020 10 20;10(1):17762. Epub 2020 Oct 20.

Institute of Molecular and Cell Biology, Singapore, 138673, Singapore.

Biologics such as peptides and antibodies are a well-established class of therapeutics. However, their intracellular delivery remains problematic. In particular, methods to efficiently inhibit intra-nuclear targets are lacking. Read More

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October 2020

Taking the Scenic Route: Polyomaviruses Utilize Multiple Pathways to Reach the Same Destination.

Viruses 2020 10 15;12(10). Epub 2020 Oct 15.

Department of Molecular and Biomedical Sciences, The University of Maine, Orono, ME 04469, USA.

Members of the family differ in their host range, pathogenesis, and disease severity. To date, some of the most studied polyomaviruses include human JC, BK, and Merkel cell polyomavirus and non-human subspecies murine and simian virus 40 (SV40) polyomavirus. Although dichotomies in host range and pathogenesis exist, overlapping features of the infectious cycle illuminate the similarities within this virus family. Read More

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October 2020

Multisynchrony in Active Microfilaments.

Authors:
Yi Man Eva Kanso

Phys Rev Lett 2020 Oct;125(14):148101

Department of Aerospace and Mechanical Engineering, University of Southern California, Los Angeles, California 90089, USA.

Biological microfilaments exhibit a variety of synchronization modes. Recent experiments observed that a pair of isolated eukaryotic flagella, coupled solely via the fluid medium, display synchrony at nontrivial phase lags in addition to in-phase and antiphase synchrony. Using an elastohydrodynamic filament model in conjunction with numerical simulations and a Floquet-type theoretical analysis, we demonstrate that it is possible to reach multiple synchronization states by varying the intrinsic activity of the filament and the strength of hydrodynamic coupling between the two filaments. Read More

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October 2020

An Analytical Microdosimetric Model for Radioimmunotherapeutic Alpha Emitters.

Radiat Res 2020 10;194(4):403-410

Department of Radiation Oncology, Hospital of The University of Pennsylvania, Philadelphia, Pennsylvania.

In this work, we present a methodology to analytically determine microdosimetric quantities in radioimmunotherapy and targeted radiotherapy with alpha particles. Monte Carlo simulations using the Geant4-DNA toolkit, which provides interaction models at the microscopic level, are performed for monoenergetic alpha particles traversing spherical sites with diameters of 1, 5 and 10 µm. An analytical function is fitted against the data in each case to model the energy imparted by monoenergetic particles to the site, as well as the variance of the distribution of energy imparted. Read More

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October 2020

Nuclear crowding and nonlinear diffusion during interkinetic nuclear migration in the zebrafish retina.

Elife 2020 10 6;9. Epub 2020 Oct 6.

Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdom.

An important question in early neural development is the origin of stochastic nuclear movement between apical and basal surfaces of neuroepithelia during interkinetic nuclear migration. Tracking of nuclear subpopulations has shown evidence of diffusion - mean squared displacements growing linearly in time - and suggested crowding from cell division at the apical surface drives basalward motion. Yet, this hypothesis has not yet been tested, and the forces involved not quantified. Read More

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October 2020