Academic literature on the topic 'Linker-less'

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Journal articles on the topic "Linker-less":

1

Plater, M. John, Abbie J. Esslemont, and William T. A. Harrison. "Porous and Close Packed Supramolecular Assemblies from 2,4-Difluoronitrobenzene with Three Different Linkers and an n-Butylamine Cap." International Journal of Molecular Sciences 24, no. 19 (September 28, 2023): 14683. http://dx.doi.org/10.3390/ijms241914683.

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A porous structure formed from sheets with cavities and two close packed structures were crystallised from building blocks prepared from 2,4-difluoronitrobenzene, a diamine linker and n-butylamine. The porous structure crystallised from a flexible building block prepared using 1,4-diaminobutane as linker. The close packed structures were prepared using either piperazine or 1,4-bis(aminomethyl)benzene as a linker and have less conformational freedom.
2

Thielen, Nathalie, Margot Neefjes, Renske Wiegertjes, Guus van den Akker, Elly Vitters, Henk van Beuningen, Esmeralda Blaney Davidson, et al. "Osteoarthritis-Related Inflammation Blocks TGF-β’s Protective Effect on Chondrocyte Hypertrophy via (de)Phosphorylation of the SMAD2/3 Linker Region." International Journal of Molecular Sciences 22, no. 15 (July 29, 2021): 8124. http://dx.doi.org/10.3390/ijms22158124.

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Osteoarthritis (OA) is a degenerative joint disease characterized by irreversible cartilage damage, inflammation and altered chondrocyte phenotype. Transforming growth factor-β (TGF-β) signaling via SMAD2/3 is crucial for blocking hypertrophy. The post-translational modifications of these SMAD proteins in the linker domain regulate their function and these can be triggered by inflammation through the activation of kinases or phosphatases. Therefore, we investigated if OA-related inflammation affects TGF-β signaling via SMAD2/3 linker-modifications in chondrocytes. We found that both Interleukin (IL)-1β and OA-synovium conditioned medium negated SMAD2/3 transcriptional activity in chondrocytes. This inhibition of TGF-β signaling was enhanced if SMAD3 could not be phosphorylated on Ser213 in the linker region and the inhibition by IL-1β was less if the SMAD3 linker could not be phosphorylated at Ser204. Our study shows evidence that inflammation inhibits SMAD2/3 signaling in chondrocytes via SMAD linker (de)-phosphorylation. The involvement of linker region modifications may represent a new therapeutic target for OA.
3

Thiriet, C., and J. J. Hayes. "Assembly into chromatin and subtype-specific transcriptional effects of exogenous linker histones directly introduced into a living Physarum cell." Journal of Cell Science 114, no. 5 (March 1, 2001): 965–73. http://dx.doi.org/10.1242/jcs.114.5.965.

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The apparent diversity of linker histone subtypes may be related to their specific roles in defining functional states of chromatin in vivo. We have developed a novel method to study constitutive peptides throughout the cell cycle and have demonstrated that an exogenous linker histone could be introduced into a living cell of the slime mold Physarum polycephalum. Here, we have used this method to assess the functional differences between three somatic linker histone subtypes in vivo, and to demonstrate the general applicability of this method. Exogenous linker histone proteins H1 degrees, H5 and H1 were directly absorbed into living cell segments of the naturally synchronous Physarum macroplasmodia at precise cell cycle stages. Fluorescence microscopy, native nucleoprotein gels and immunoblotting of nuclei and chromatin with subtype-specific antibodies revealed that exogenous linker histones were efficiently transported into nuclei and were integrated into chromatin. The immunoreactivity of a preparation of anti-H1 degrees antibodies that are blocked from binding to specific H1 degrees epitopes in native chromatin indicates that the exogenous linker histones were similarly associated into Physarum chromatin. Interestingly, linker histones were found to be less stably associated with Physarum chromatin during S-phase than during G(2)-phase. Furthermore, we show that exogenous linker histones incorporated in early G(2)-phase inhibited transcription and that the level of inhibition correlates with the apparent role of the linker histone subtype in regulating transcription in cells where it normally occurs.
4

BLACK, Gary W., Jane E. RIXON, Jonathan H. CLARKE, Geoffrey P. HAZLEWOOD, Michael K. THEODOROU, Philip MORRIS, and Harry J. GILBERT. "Evidence that linker sequences and cellulose-binding domains enhance the activity of hemicellulases against complex substrates." Biochemical Journal 319, no. 2 (October 15, 1996): 515–20. http://dx.doi.org/10.1042/bj3190515.

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Xylanase A (XYLA) and arabinofuranosidase C (XYLC) from Pseudomonas fluorescens subsp. cellulosa are modular enzymes consisting of discrete cellulose-binding domains (CBDs) and catalytic domains joined by serine-rich linker sequences. To evaluate the role of the CBDs and interdomain regions, the capacity of full-length and truncated derivatives of the two enzymes, lacking either the linker sequences or CBDs, to hydrolyse a range of substrates, and bind to cellulose, was determined. Removal of the CBDs did not affect either the activity of XYLA or XYLC against soluble arabinoxylan. Similarly, deletion of the linker sequences did not alter the affinity of the enzymes for cellulose or their activity against soluble substrates, even when bound to cellulose via the CBDs. Truncated derivatives of XYLA lacking either the linker sequences or the CBD were less active against xylan contained in cellulose-hemicellulose complexes, compared with the full-length xylanase. Similarly, removal of the CBD from XYLC diminished the activity of the enzyme (XYLC´´´) against plant-cell-wall material containing highly substituted arabinoxylan. The role of CBDs and linker sequences in the catalytic activity of hemicellulases against the plant cell wall is discussed.
5

Mathur, Rajesh, Jie Zheng, Yangyang Yan, and Fred J. Sigworth. "Role of the S3-S4 Linker in Shaker Potassium Channel Activation." Journal of General Physiology 109, no. 2 (February 1, 1997): 191–99. http://dx.doi.org/10.1085/jgp.109.2.191.

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Structural models of voltage-gated channels suggest that flexibility of the S3-S4 linker region may be important in allowing the S4 region to undergo large conformational changes in its putative voltage-sensing function. We report here the initial characterization of 18 mutations in the S3-S4 linker of the Shaker channel, including deletions, insertions, charge changes, substitution of prolines, and chimeras replacing the 25-residue Shaker linker with 7- or 9-residue sequences from Shab, Shaw, or Shal. As measured in Xenopus oocytes with a two-microelectrode voltage clamp, each mutant construct yielded robust currents. Changes in the voltage dependence of activation were small, with activation voltage shifts of 13 mV or less. Substitution of linkers from the slowly activating Shab and Shaw channels resulted in a three- to fourfold slowing of activation and deactivation. It is concluded that the S3-S4 linker is unlikely to participate in a large conformational change during channel activation. The linker, which in some channel subfamilies has highly conserved sequences, may however be a determinant of activation kinetics in potassium channels, as previously has been suggested in the case of calcium channels.
6

Tomar, Rachana, Pankaj Sharma, Ankit Srivastava, Saurabh Bansal, Ashish, and Bishwajit Kundu. "Structural and functional insights into an archaealL-asparaginase obtained through the linker-less assembly of constituent domains." Acta Crystallographica Section D Biological Crystallography 70, no. 12 (November 22, 2014): 3187–97. http://dx.doi.org/10.1107/s1399004714023414.

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Covalent linkers bridging the domains of multidomain proteins are considered to be crucial for assembly and function. In this report, an exception in which the linker of a two-domain dimeric L-asparaginase fromPyrococcus furiosus(PfA) was found to be dispensable is presented. Domains of this enzyme assembled without the linker into a conjoined tetrameric form that exhibited higher activity than the parent enzyme. The global shape and quaternary structure of the conjoined PfA were also similar to the wild-type PfA, as observed by their solution scattering profiles and X-ray crystallographic data. Comparison of the crystal structures of substrate-bound and unbound enzymes revealed an altogether new active-site composition and mechanism of action. Thus, conjoined PfA is presented as a unique enzyme obtained through noncovalent, linker-less assembly of constituent domains that is stable enough to function efficiently at elevated temperatures.
7

Al-Kutubi, Hanan, Alla Dikhtiarenko, Hamid Reza Zafarani, Ernst J. R. Sudhölter, Jorge Gascon, and Liza Rassaei. "Facile formation of ZIF-8 thin films on ZnO nanorods." CrystEngComm 17, no. 29 (2015): 5360–64. http://dx.doi.org/10.1039/c5ce00590f.

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Shi, Fei, Song Qin, and Yin-Chu Wang. "The Coevolution of Phycobilisomes: Molecular Structure Adapting to Functional Evolution." Comparative and Functional Genomics 2011 (2011): 1–9. http://dx.doi.org/10.1155/2011/230236.

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Phycobilisome is the major light-harvesting complex in cyanobacteria and red alga. It consists of phycobiliproteins and their associated linker peptides which play key role in absorption and unidirectional transfer of light energy and the stability of the whole complex system, respectively. Former researches on the evolution among PBPs and linker peptides had mainly focused on the phylogenetic analysis and selective evolution. Coevolution is the change that the conformation of one residue is interrupted by mutation and a compensatory change selected for in its interacting partner. Here, coevolutionary analysis of allophycocyanin, phycocyanin, and phycoerythrin and covariation analysis of linker peptides were performed. Coevolution analyses reveal that these sites are significantly correlated, showing strong evidence of the functional and structural importance of interactions among these residues. According to interprotein coevolution analysis, less interaction was found between PBPs and linker peptides. Our results also revealed the correlations between the coevolution and adaptive selection in PBS were not directly related, but probably demonstrated by the sites coupled under physical-chemical interactions.
9

Bašić, Ivana, and Irena Zovko Dinković. "Sintaktički, značenjski i uporabni status složenog veznika kao i." Jezikoslovlje 23, no. 2 (January 11, 2023): 281–99. http://dx.doi.org/10.29162/jez.2022.11.

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This paper examines coordinated structures introduced by means of the multi-word linker kao i, which can link syntactic units ranging from phrases, clause constituents and clauses to sentences and parts of discourse. We first discuss the coordinating properties of the linker – structural independence, order of conjoining, concord – as well as its usage and interchangeability with other single and multi-word linkers and correlatives. Together with the structural properties, different meanings of the linker are discussed, namely, its core meaning of addition, complemented by the meanings of comparison or gradation. When used in its comparative meaning, the linker kao i links units in parenthetic coordination and is interchangeable with the preposition poput, while its usage in the meaning of gradation is similar to the usage of the correlative coordinator ne samo... nego/već. Although most of its syntactic properties would place the linker kao i in the category of coordinators with additive meaning, its meaning does not fully correspond with the meanings of single-word coordinators i and te, multi-word coordinators a i and ali i or the correlative i... i, with which it generally bears most resemblance and is largely interchangeable. The difference is that kao i exhibits some properties typical of either subordinated or juxtaposed structures, for example, a lower degree of conceptual distance and instability in terms of concord. To further investigate these findings, we compared the multi-word linker kao i to its corresponding linker in English, as well as, and concluded that in both languages these linkers are less prototypical additive coordinators that frequently express parenthetic (additional information) coordination of comparative or gradational nature.
10

Zhang, Shaodong, Ralph-Olivier Moussodia, Sabine Vértesy, Sabine André, Michael L. Klein, Hans-Joachim Gabius, and Virgil Percec. "Unraveling functional significance of natural variations of a human galectin by glycodendrimersomes with programmable glycan surface." Proceedings of the National Academy of Sciences 112, no. 18 (April 20, 2015): 5585–90. http://dx.doi.org/10.1073/pnas.1506220112.

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Surface-presented glycans (complex carbohydrates) are docking sites for adhesion/growth-regulatory galectins within cell–cell/matrix interactions. Alteration of the linker length in human galectin-8 and single-site mutation (F19Y) are used herein to illustrate the potential of glycodendrimersomes with programmable glycan displays as a model system to reveal the functional impact of natural sequence variations in trans recognition. Extension of the linker length slightly reduces lectin capacity as agglutinin and slows down aggregate formation at low ligand surface density. The mutant protein is considerably less active as agglutinin and less sensitive to low-level ligand presentation. The present results suggest that mimicking glycan complexity and microdomain occurrence on the glycodendrimersome surface can provide key insights into mechanisms to accomplish natural selectivity and specificity of lectins in structural and topological terms.

Dissertations / Theses on the topic "Linker-less":

1

Turelli, Lorenzo. "Étude de nouveaux motifs d'espaceurs dans la construction de conjugués anticorps-médicaments." Electronic Thesis or Diss., Strasbourg, 2023. http://www.theses.fr/2023STRAF063.

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La classe des conjugués anticorps-médicaments (ADC) représente l'un des traitements à la croissance la plus rapide en oncologie, permettant l'utilisation de composés hautement cytotoxiques liés de manière covalente à un anticorps monoclonal (mAb) qui peut se fixer sélectivement à un antigène exprimé à la surface de la cellule cancéreuse, assurant ainsi la précision de cette thérapie. Le motif de liaison, qui relie le mAb au médicament, est essentiel pour contrôler la libération du médicament ainsi que pour la pharmacocinétique et la pharmacodynamique de l'ensemble du conjugué. Cependant, le développement d'un nouveau linker est un processus long et coûteux, dans lequel le motif idéal doit assurer à la fois la stabilité en circulation sanguine et une cinétique rapide dans la libération du médicament à l'intérieur de la cellule cancéreuse. Le travail décrit ici vise à répondre aux limitations présentes dans ce domaine de deux manières différentes : premièrement, en introduisant un nouveau linker clivable sensible à l'acide avec une excellente stabilité extracellulaire et une clivabilité sélective dans la cellule cancéreuse ; deuxièmement, en adoptant une approche sans linker, en introduisant un nouveau format d'ADC, appelé Self Drugged Antibody (SDA), dans lequel le médicament est construit sur le mAb par une réaction multicomposant Ugi
The class of Antibody Drug Conjugates (ADCs) represents one of the most fast-growing treatments in oncology therapeutics, enabling the use of highly cytotoxic compounds covalently linked to a monoclonal antibody (mAb) which can selectively get attached to an antigen expressed on the surface of the cancer cell, assuring the precision of this therapy. The linker motif, connecting the mAb to the drug, is key to dictate the modality of the drug’s release as for the pharmacokinetic and pharmacodynamic of the whole conjugate. However, the development of a novel linker is a costly and time-consuming process, in which the ideal motif has to assure both the stability in blood circulation and a fast kinetic in the release of the warhead inside the cancer cell. The work here described aims at addressing the limitations present in this field in two different ways: first by introducing a novel acid sensitive cleavable linker with excellent extracellular stability and selective cleavability in the cancer cell; secondly, embracing a linker-less approach, by introducing a new format of ADC, coined Self Drugged Antibody (SDA), in which the drug is built on the mAb through a Ugi multicomponent reaction

Conference papers on the topic "Linker-less":

1

Kellie, Benjamin, and Shaurya Prakash. "Fabrication of Ceramic High Temperature Microsystems." In ASME 2011 International Mechanical Engineering Congress and Exposition. ASMEDC, 2011. http://dx.doi.org/10.1115/imece2011-64476.

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This paper reports on recent advances in fabricating alumina-based ceramic microcombustors for applications in high temperature microsystems. We have fabricated alumina structures with critical dimensions on the order of 1 mm or less by using a gel-casting approach with poly(vinyl) alcohol (PVA) as a non-toxic polymeric binder. Polymer binder content, alumina weight ratio, and thermal cycling were varied systematically to develop microcombustors that can sustain stable flames in a spiral configuration allowing for better mixing of fuel and oxidizer streams for a more uniform heat output. The polymer binder and cross-linker content varied between 10 and 20% (w/v to DI water) and 50 and 100% (w/w to PVA) respectively to obtain an optimal binder content. The weight ratio of alumina (w/w 30–50%) in the binder solution was evaluated with 1.1 micron particles to observe the effect on the green body density. The green body was then fired in a high temperature furnace in air to burn-out the polymeric binder and sinter the ceramic. Heating and cooling rates, maximum operation temperature, and dwell times were evaluated to obtain high density ceramic structures with 50% or higher alumina content. Thermal stress and heating and cooling rates appear to be major parameters to control in order to obtain high-quality microcombustors.

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