scholarly journals Regulated Expression of nullo Is Required for the Formation of Distinct Apical and Basal Adherens Junctions in the Drosophila Blastoderm

2000 ◽  
Vol 150 (2) ◽  
pp. 391-402 ◽  
Author(s):  
Christine Hunter ◽  
Eric Wieschaus
Keyword(s):  
Large Scale ◽  
De Novo ◽  
Adherens Junctions ◽  
Leading Edge ◽  
Drosophila Embryo ◽  
The Novel ◽  
Junction Formation ◽  
Morphological Defects ◽  
The Many ◽  
And Function

During cellularization, the Drosophila embryo undergoes a large-scale cytokinetic event that packages thousands of syncytial nuclei into individual cells, resulting in the de novo formation of an epithelial monolayer in the cortex of the embryo. The formation of adherens junctions is one of the many aspects of epithelial polarity that is established during cellularization: at the onset of cellularization, the Drosophila β-catenin homologue Armadillo (Arm) accumulates at the leading edge of the cleavage furrow, and later to the apicolateral region where the zonula adherens precursors are formed. In this paper, we show that the basal accumulation of Arm colocalizes with DE-cadherin and Dα-catenin, and corresponds to a region of tight membrane association, which we refer to as the basal junction. Although the two junctions are similar in components and function, they differ in their response to the novel cellularization protein Nullo. Nullo is present in the basal junction and is required for its formation at the onset of cellularization. In contrast, Nullo is degraded before apical junction formation, and prolonged expression of Nullo blocks the apical clustering of junctional components, leading to morphological defects in the developing embryo. These observations reveal differences in the formation of the apical and basal junctions, and offer insight into the role of Nullo in basal junction formation.

scholarly journals Limited role of differential fractionation in genome content variation and function in maize (Zea mays L.) inbred lines

2017 ◽  
Author(s):  
Alex B. Brohammer ◽  
Thomas JY. Kono ◽  
Nathan M. Springer ◽  
Suzanne E. McGaugh ◽  
Candice N. Hirsch
Keyword(s):  
Large Scale ◽  
De Novo ◽  
Duplicate Gene ◽  
Duplication Event ◽  
Inbred Lines ◽  
Whole Genome ◽  
Ancestral State ◽  
Genome Duplication Event ◽  
Number Variation ◽  
And Function

SUMMARYMaize is a diverse paleotetraploid species with widespread presence/absence variation and copy number variation. One mechanism through which presence/absence variation can arise is differential fractionation. Fractionation refers to the loss of duplicate gene pairs from one of the maize subgenomes during diploidization and differential fractionation refers to non-shared gene loss events between individuals. We investigated the prevalence of presence/absence variation resulting from differential fractionation in the syntenic portion of the genome using two whole genome de novo assemblies of the inbred lines B73 and PH207. Between these two genomes, syntenic genes were highly conserved with less than 1% of syntenic genes being subject to differential fractionation. The few variable syntenic genes that were identified are unlikely to contribute to functional phenotypic variation, as there is a significant depletion of these genes in annotated gene sets. In further comparisons of 60 diverse inbred lines, non-syntenic genes were six times more likely to be variable compared to syntenic genes, suggesting that comparisons among additional genome assemblies are not likely to result in the discovery of large-scale presence/absence variation among syntenic genes.SIGNIFICANCE STATEMENTThere is a large amount of presence/absence variation for gene content in maize. One mechanism that has been hypothesized to contribute to this variation is differential fractionation between individuals following the maize whole genome duplication event. Using comparative genomics, with sorghum and rice representing the ancestral state, we observed little evidence of differential fractionation among elite inbred lines and the few differentially fractionated genes identified did not appear to confer functional significance.

scholarly journals DLG-1 Is a MAGUK Similar to SAP97 and Is Required for Adherens Junction Formation

2001 ◽  
Vol 12 (11) ◽  
pp. 3465-3475 ◽  
Author(s):  
Bonnie L. Firestein ◽  
Christopher Rongo
Keyword(s):  
Cell Polarity ◽  
Adherens Junctions ◽  
Adherens Junction ◽  
Cell Junctions ◽  
Permeability Barrier ◽  
Cortical Actin ◽  
Interaction Domain ◽  
Amino Terminal ◽  
Junction Formation ◽  
And Function

Cellular junctions are critical for intercellular communication and for the assembly of cells into tissues. Cell junctions often consist of tight junctions, which form a permeability barrier and prevent the diffusion of lipids and proteins between cell compartments, and adherens junctions, which control the adhesion of cells and link cortical actin filaments to attachment sites on the plasma membrane. Proper tight junction formation and cell polarity require the function of membrane-associated guanylate kinases (MAGUKs) that contain the PDZ protein-protein interaction domain. In contrast, less is known about how adherens junctions are assembled. Here we describe how the PDZ-containing protein DLG-1 is required for the proper formation and function of adherens junctions in Caenorhabditis elegans. DLG-1 is a MAGUK protein that is most similar in sequence to mammalian SAP97, which is found at both synapses of the CNS, as well as at cell junctions of epithelia. DLG-1 is localized to adherens junctions, and DLG-1 localization is mediated by an amino-terminal domain shared with SAP97 but not found in other MAGUK family members. DLG-1 recruits other proteins and signaling molecules to adherens junctions, while embryos that lack DLG-1 fail to recruit the proteins AJM-1 and CPI-1 to adherens junctions. DLG-1 is required for the proper organization of the actin cytoskeleton and for the morphological elongation of embryos. In contrast to other proteins that have been observed to affect adherens junction assembly and function, DLG-1 is not required to maintain cell polarity. Our results suggest a new function for MAGUK proteins distinct from their role in cell polarity.

Not Just a Simple Sugar: Arabinose Metabolism and Function in Plants

2021 ◽  
Author(s):  
Alban Mariette ◽  
Hee Sung Kang ◽  
Joshua L Heazlewood ◽  
Staffan Persson ◽  
Berit Ebert ◽  
...  
Keyword(s):  
Cell Wall ◽  
De Novo ◽  
Research Area ◽  
Land Plant ◽  
Future Research ◽  
Wall Structures ◽  
The Many ◽  
And Function ◽  
Simple Sugar ◽  
Development Structure

Abstract Growth, development, structure as well as dynamic adaptations and remodelling processes in plants are largely controlled by the properties of their cell walls. These intricate wall structures are mostly made up of different sugars connected through specific glycosidic linkages but also contain many glycosylated proteins. A key plant sugar that is present throughout the plantae, even before the divergence of the land plant lineage, but is not found in animals, is L-Arabinose (L-Ara). Here, we summarize and discuss the processes and proteins involved in L-Ara de novo synthesis, L-Ara interconversion, and the assembly and recycling of L-Ara-containing cell wall polymers and proteins. We also discuss the biological function of L-Ara in a context focused manner, mainly addressing cell wall related functions that are conferred by the basic physical properties of arabinose containing polymers/compounds. In this article we explore these processes with the goal of directing future research efforts to the many exciting yet unanswered questions in this research area.

Plant hormones, plant growth regulators

2014 ◽  
Vol 155 (26) ◽  
pp. 1011-1018 ◽  
Author(s):  
György Végvári ◽  
Edina Vidéki
Keyword(s):  
Nervous System ◽  
Growth And Development ◽  
Large Scale ◽  
Essential Role ◽  
Higher Plants ◽  
Structure And Function ◽  
Wide Sense ◽  
Large Scale Integration ◽  
Scale Integration ◽  
And Function

Plants seem to be rather defenceless, they are unable to do motion, have no nervous system or immune system unlike animals. Besides this, plants do have hormones, though these substances are produced not in glands. In view of their complexity they lagged behind animals, however, plant organisms show large scale integration in their structure and function. In higher plants, such as in animals, the intercellular communication is fulfilled through chemical messengers. These specific compounds in plants are called phytohormones, or in a wide sense, bioregulators. Even a small quantity of these endogenous organic compounds are able to regulate the operation, growth and development of higher plants, and keep the connection between cells, tissues and synergy beween organs. Since they do not have nervous and immume systems, phytohormones play essential role in plants’ life. Orv. Hetil., 2014, 155(26), 1011–1018.

Target-Templated de novo Design of Macrocyclic D-/L-Peptides: Inhibitors of the PD-1/PD-L1 Interaction

2020 ◽  
Author(s):  
Salvador Guardiola ◽  
Monica Varese ◽  
Xavier Roig ◽  
Jesús Garcia ◽  
Ernest Giralt
Keyword(s):  
Protein Interactions ◽  
Cyclic Peptides ◽  
General Framework ◽  
Large Scale ◽  
De Novo ◽  
Inhibitory Effect ◽  
Original Text ◽  
Protein Protein Interactions ◽  
Retraction Notice ◽  
Pharmaceutical Properties

<p>NOTE: This preprint has been retracted by consensus from all authors. See the retraction notice in place above; the original text can be found under "Version 1", accessible from the version selector above.</p><p><br></p><p>------------------------------------------------------------------------</p><p><br></p><p>Peptides, together with antibodies, are among the most potent biochemical tools to modulate challenging protein-protein interactions. However, current structure-based methods are largely limited to natural peptides and are not suitable for designing target-specific binders with improved pharmaceutical properties, such as macrocyclic peptides. Here we report a general framework that leverages the computational power of Rosetta for large-scale backbone sampling and energy scoring, followed by side-chain composition, to design heterochiral cyclic peptides that bind to a protein surface of interest. To showcase the applicability of our approach, we identified two peptides (PD-<i>i</i>3 and PD-<i>i</i>6) that target PD-1, a key immune checkpoint, and work as protein ligand decoys. A comprehensive biophysical evaluation confirmed their binding mechanism to PD-1 and their inhibitory effect on the PD-1/PD-L1 interaction. Finally, elucidation of their solution structures by NMR served as validation of our <i>de novo </i>design approach. We anticipate that our results will provide a general framework for designing target-specific drug-like peptides.<i></i></p>

A Target-Based Method for Designing Heterochiral Cyclic Peptide Binders: De Novo Inhibitors of the PD-1/PD-L1 Interaction

2020 ◽  
Author(s):  
Salvador Guardiola ◽  
Monica Varese ◽  
Xavier Roig ◽  
Jesús Garcia ◽  
Ernest Giralt
Keyword(s):  
Protein Interactions ◽  
Cyclic Peptides ◽  
General Framework ◽  
Large Scale ◽  
Cyclic Peptide ◽  
De Novo ◽  
Inhibitory Effect ◽  
Original Text ◽  
Retraction Notice ◽  
Pharmaceutical Properties

<p>NOTE: This preprint has been retracted by consensus from all authors. See the retraction notice in place above; the original text can be found under "Version 1", accessible from the version selector above.</p><p><br></p><p>------------------------------------------------------------------------</p><p><br></p><p>Peptides, together with antibodies, are among the most potent biochemical tools to modulate challenging protein-protein interactions. However, current structure-based methods are largely limited to natural peptides and are not suitable for designing target-specific binders with improved pharmaceutical properties, such as macrocyclic peptides. Here we report a general framework that leverages the computational power of Rosetta for large-scale backbone sampling and energy scoring, followed by side-chain composition, to design heterochiral cyclic peptides that bind to a protein surface of interest. To showcase the applicability of our approach, we identified two peptides (PD-<i>i</i>3 and PD-<i>i</i>6) that target PD-1, a key immune checkpoint, and work as protein ligand decoys. A comprehensive biophysical evaluation confirmed their binding mechanism to PD-1 and their inhibitory effect on the PD-1/PD-L1 interaction. Finally, elucidation of their solution structures by NMR served as validation of our <i>de novo </i>design approach. We anticipate that our results will provide a general framework for designing target-specific drug-like peptides.<i></i></p>

Target-Templated de novo Design of Macrocyclic D-/L-Peptides: Inhibitors of the PD-1/PD-L1 Interaction

2020 ◽  
Author(s):  
Salvador Guardiola ◽  
Monica Varese ◽  
Xavier Roig ◽  
Jesús Garcia ◽  
Ernest Giralt
Keyword(s):  
Protein Interactions ◽  
Cyclic Peptides ◽  
General Framework ◽  
Large Scale ◽  
De Novo ◽  
Inhibitory Effect ◽  
Original Text ◽  
Protein Protein Interactions ◽  
Retraction Notice ◽  
Pharmaceutical Properties

<p>NOTE: This preprint has been retracted by consensus from all authors. See the retraction notice in place above; the original text can be found under "Version 1", accessible from the version selector above.</p><p><br></p><p>------------------------------------------------------------------------</p><p><br></p><p>Peptides, together with antibodies, are among the most potent biochemical tools to modulate challenging protein-protein interactions. However, current structure-based methods are largely limited to natural peptides and are not suitable for designing target-specific binders with improved pharmaceutical properties, such as macrocyclic peptides. Here we report a general framework that leverages the computational power of Rosetta for large-scale backbone sampling and energy scoring, followed by side-chain composition, to design heterochiral cyclic peptides that bind to a protein surface of interest. To showcase the applicability of our approach, we identified two peptides (PD-<i>i</i>3 and PD-<i>i</i>6) that target PD-1, a key immune checkpoint, and work as protein ligand decoys. A comprehensive biophysical evaluation confirmed their binding mechanism to PD-1 and their inhibitory effect on the PD-1/PD-L1 interaction. Finally, elucidation of their solution structures by NMR served as validation of our <i>de novo </i>design approach. We anticipate that our results will provide a general framework for designing target-specific drug-like peptides.<i></i></p>

Covalent Atomic Bridges Enable Unidirectional Enhancement of Electronic Transport in Aligned Carbon Nanotubes

2019 ◽  
Author(s):  
Mingguang Chen ◽  
Wangxiang Li ◽  
Anshuman Kumar ◽  
Guanghui Li ◽  
Mikhail Itkis ◽  
...  
Keyword(s):  
Carbon Nanotubes ◽  
Electrical Transport ◽  
Large Scale ◽  
The Novel ◽  
Electrical Measurements ◽  
Metal Atoms ◽  
Aligned Carbon Nanotubes ◽  
Transport Channels ◽  
Walled Carbon Nanotubes ◽  
Bulk Structures

<p>Interconnecting the surfaces of nanomaterials without compromising their outstanding mechanical, thermal, and electronic properties is critical in the design of advanced bulk structures that still preserve the novel properties of their nanoscale constituents. As such, bridging the p-conjugated carbon surfaces of single-walled carbon nanotubes (SWNTs) has special implications in next-generation electronics. This study presents a rational path towards improvement of the electrical transport in aligned semiconducting SWNT films by deposition of metal atoms. The formation of conducting Cr-mediated pathways between the parallel SWNTs increases the transverse (intertube) conductance, while having negligible effect on the parallel (intratube) transport. In contrast, doping with Li has a predominant effect on the intratube electrical transport of aligned SWNT films. Large-scale first-principles calculations of electrical transport on aligned SWNTs show good agreement with the experimental electrical measurements and provide insight into the changes that different metal atoms exert on the density of states near the Fermi level of the SWNTs and the formation of transport channels. </p>

Integration of Ecological and Engineering Aspects in Planning Large Scale Tidal Power Development in the Bay of Fundy, Canada

1984 ◽  
Vol 16 (1-2) ◽  
pp. 281-295 ◽  
Author(s):  
Donald C Gordon
Keyword(s):  
Large Scale ◽  
Feasibility Studies ◽  
Bay Of Fundy ◽  
Final Decision ◽  
Power Development ◽  
Tidal Power ◽  
History Of ◽  
Scientists And Engineers ◽  
The Many ◽  
University Scientists

Large-scale tidal power development in the Bay of Fundy has been given serious consideration for over 60 years. There has been a long history of productive interaction between environmental scientists and engineers durinn the many feasibility studies undertaken. Up until recently, tidal power proposals were dropped on economic grounds. However, large-scale development in the upper reaches of the Bay of Fundy now appears to be economically viable and a pre-commitment design program is highly likely in the near future. A large number of basic scientific research studies have been and are being conducted by government and university scientists. Likely environmental impacts have been examined by scientists and engineers together in a preliminary fashion on several occasions. A full environmental assessment will be conducted before a final decision is made and the results will definately influence the outcome.

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