scholarly journals Engaging the ‘A’ Class Antibody: Variable-Heavy (VH) region influencing IgA1&2 engagement of FcαRI and superantigen proteins G, A, and L

2021 ◽  
Author(s):  
Wei-Li Ling ◽  
Chinh Tran-To Su ◽  
Wai-Heng Lua ◽  
Joshua Yi Yeo ◽  
Jun-Jie Poh ◽  
...  
Keyword(s):  
Mucosal Surfaces ◽  
Variable Heavy ◽  
Sterically Hinder ◽  
Bacterial Superantigens ◽  
V Region ◽  
Cdr Grafting ◽  
Her2 Antigen ◽  
Suitable Framework ◽  
Insight Into ◽  
Class Antibody

AbstractInterest in IgA as an alternative therapeutic and diagnostic antibody has increased over the years, yet much remains to be investigated especially given their importance in activating immune cells in blood and in mucosal immunity. Recent whole antibody-based investigations have shown significant distal effects between the variable (V) and constant (C)-regions that can be mitigated by the different hinge regions of the human IgA subtypes A1 and A2. Diving deeper into the mechanisms underlying this, systematic VH manipulations retaining the CDRs were performed on a panel of 28 IgA1s and A2s across the Trastuzumab and Pertuzumab models, revealed distal effects on FcαRI binding. Further insights from structural modelling showed these effects to also be mitigated by the differing glycosylation patterns in IgA1 and 2 to explain reversal of trends of IgA1s and 2s effected by slight changes in the CDRs. IgAs bound at the Fc showed similar trends but magnitudes better binding to Her2 with that bound by ppL, showing that ppL can sterically hinder Her2 antigen binding. Contrary to canonical knowledge, we found strong evidence of IgAs binding SpG that was narrowed to be at the CH2-3 region, and that the likely binding with SpA was beyond VH3 FWR and most likely at the CH1. VH1 was found to be the most suitable framework (FWRs) for CDR-grafting for both IgA1 and 2. With relevance to interactions with the microbiome at mucosal surfaces, mechanistic insight of how these IgAs can interact bacterial superantigens proteins G, A, and L are also discovered for potential future interventions.One Sentence SummaryAn insight into the mechanism of distal V-region effects on FCAR and superantigens proteins G, A, and L by both IgA1 and A2.

scholarly journals Factors Facilitating the Implementation of the Sustainable Development Goals in Regional and Local Planning—Experiences from Norway

2021 ◽  
Vol 13 (8) ◽  
pp. 4282
Author(s):  
Kjersti Granås Bardal ◽  
Mathias Brynildsen Reinar ◽  
Aase Kristine Lundberg ◽  
Maiken Bjørkan
Keyword(s):  
Sustainable Development ◽  
Regional Planning ◽  
Sustainable Development Goals ◽  
Successful Implementation ◽  
Local Planning ◽  
The Sustainable Development ◽  
Institutional Contexts ◽  
Development Goals ◽  
Suitable Framework ◽  
Insight Into

Successful implementation of the Sustainable Development Goals (SDGs) depends on regional and local authorities’ ability to implement the goals in their respective contexts. Through a survey and interviews with informants in Norwegian municipalities and county councils, this paper explores and offers new empirical insight into (1) which factors can be identified as facilitating the implementation of the SDGs in Norwegian local and regional planning; (2) how the facilitating factors are conditioned by the different local and regional institutional contexts; and (3) how these factors from the Norwegian context correspond or differ from those in the international literature. We find that the existing Planning and Building Act is considered a suitable framework for the implementation of the SDGs in the Norwegian context, and that the SDGs are high on the national and regional governmental agendas. However, work remains in integrating the SDGs into underlying governmental activities. They must be incorporated into action plans and planning tools, which will require involvement, collaboration and development work across sectors and authority levels, and the development of guidelines for how this can be done. Allocating enough resources for this work will be crucial, and smaller municipalities may need other types and degrees of support than larger ones.

scholarly journals Bioprospecting Antimicrobials from Lactiplantibacillus plantarum: Key Factors Underlying Its Probiotic Action

2021 ◽  
Vol 22 (21) ◽  
pp. 12076
Author(s):  
Maria Teresa Rocchetti ◽  
Pasquale Russo ◽  
Vittorio Capozzi ◽  
Djamel Drider ◽  
Giuseppe Spano ◽  
...  
Keyword(s):  
Therapeutic Potential ◽  
Antiviral Agents ◽  
Key Factors ◽  
Emerging Trends ◽  
Mucosal Surfaces ◽  
Host Health ◽  
Health Promoting ◽  
Conventional Antibiotics ◽  
Insight Into

Lactiplantibacillus plantarum (L. plantarum) is a well-studied and versatile species of lactobacilli. It is found in several niches, including human mucosal surfaces, and it is largely employed in the food industry and boasts a millenary tradition of safe use, sharing a long-lasting relationship with humans. L. plantarum is generally recognised as safe and exhibits a strong probiotic character, so that several strains are commercialised as health-promoting supplements and functional food products. For these reasons, L. plantarum represents a valuable model to gain insight into the nature and mechanisms of antimicrobials as key factors underlying the probiotic action of health-promoting microbes. Probiotic antimicrobials can inhibit the growth of pathogens in the gut ensuring the intestinal homeostasis and contributing to the host health. Furthermore, they may be attractive alternatives to conventional antibiotics, holding potential in several biomedical applications. The aim of this review is to investigate the most relevant papers published in the last ten years, bioprospecting the antimicrobial activity of characterised probiotic L. plantarum strains. Specifically, it focuses on the different chemical nature, the action spectra and the mechanisms underlying the bioactivity of their antibacterial and antiviral agents. Emerging trends in postbiotics, some in vivo applications of L. plantarum antimicrobials, including strengths and limitations of their therapeutic potential, are addressed and discussed.

scholarly journals Quantitative and Qualitative Changes in V-J α Rearrangements During Mouse Thymocytes Differentiation

2002 ◽  
Vol 196 (9) ◽  
pp. 1163-1174 ◽  
Author(s):  
Nicolas Pasqual ◽  
Maighréad Gallagher ◽  
Catherine Aude-Garcia ◽  
Mélanie Loiodice ◽  
Florence Thuderoz ◽  
...  
Keyword(s):  
Normal Mouse ◽  
Accurate Determination ◽  
Pcr Analysis ◽  
Repertoire Size ◽  
Systematic Analysis ◽  
Qualitative And Quantitative ◽  
V Genes ◽  
V Region ◽  
Insight Into ◽  
Qualitative Changes

Knowledge of the complete nucleotide sequence of the mouse TCRAD locus allows an accurate determination V-J rearrangement status. Using multiplex genomic PCR assays and real time PCR analysis, we report a comprehensive and systematic analysis of the V-J recombination of TCR α chain in normal mouse thymocytes during development. These respective qualitative and quantitative approaches give rise to four major points describing the control of gene rearrangements. (a) The V-J recombination pattern is not random during ontogeny and generates a limited TCR α repertoire; (b) V-J rearrangement control is intrinsic to the thymus; (c) each V gene rearranges to a set of contiguous J segments with a gaussian-like frequency; (d) there are more rearrangements involving V genes at the 3′ side than 5′ end of V region. Taken together, this reflects a preferential association of V and J gene segments according to their respective positions in the locus, indicating that accessibility of both V and J regions is coordinately regulated, but in different ways. These results provide a new insight into TCR α repertoire size and suggest a scenario for V usage during differentiation.

Calibration problems in hydrogen luminosities

1966 ◽  
Vol 24 ◽  
pp. 322-330
Author(s):  
A. Beer
Keyword(s):  
Galactic Structure ◽  
B Stars ◽  
Insight Into

The investigations which I should like to summarize in this paper concern recent photo-electric luminosity determinations of O and B stars. Their final aim has been the derivation of new stellar distances, and some insight into certain patterns of galactic structure.

Stochasting modeling of planetary ring systems

1984 ◽  
Vol 75 ◽  
pp. 461-469 ◽  
Author(s):  
Robert W. Hart
Keyword(s):  
Maximum Entropy ◽  
Ring System ◽  
The Sun ◽  
Ultimate State ◽  
Interparticle Interactions ◽  
Ring Systems ◽  
First Order ◽  
Planetary Ring ◽  
Insight Into

ABSTRACTThis paper models maximum entropy configurations of idealized gravitational ring systems. Such configurations are of interest because systems generally evolve toward an ultimate state of maximum randomness. For simplicity, attention is confined to ultimate states for which interparticle interactions are no longer of first order importance. The planets, in their orbits about the sun, are one example of such a ring system. The extent to which the present approximation yields insight into ring systems such as Saturn's is explored briefly.

Skeletal elements of crinoid echinoderms: High-resolution structural and microanalytical results

1983 ◽  
Vol 41 ◽  
pp. 194-195
Author(s):  
D. F. Blake ◽  
L. F. Allard ◽  
D. R. Peacor
Keyword(s):  
High Resolution ◽  
Marine Invertebrates ◽  
Sea Urchins ◽  
Structural Features ◽  
Sea Stars ◽  
High Resolution Tem ◽  
Relationship Of ◽  
The Relationship ◽  
Insight Into

Echinodermata is a phylum of marine invertebrates which has been extant since Cambrian time (c.a. 500 m.y. before the present). Modern examples of echinoderms include sea urchins, sea stars, and sea lilies (crinoids). The endoskeletons of echinoderms are composed of plates or ossicles (Fig. 1) which are with few exceptions, porous, single crystals of high-magnesian calcite. Despite their single crystal nature, fracture surfaces do not exhibit the near-perfect {10.4} cleavage characteristic of inorganic calcite. This paradoxical mix of biogenic and inorganic features has prompted much recent work on echinoderm skeletal crystallography. Furthermore, fossil echinoderm hard parts comprise a volumetrically significant portion of some marine limestones sequences. The ultrastructural and microchemical characterization of modern skeletal material should lend insight into: 1). The nature of the biogenic processes involved, for example, the relationship of Mg heterogeneity to morphological and structural features in modern echinoderm material, and 2). The nature of the diagenetic changes undergone by their ancient, fossilized counterparts. In this study, high resolution TEM (HRTEM), high voltage TEM (HVTEM), and STEM microanalysis are used to characterize tha ultrastructural and microchemical composition of skeletal elements of the modern crinoid Neocrinus blakei.

Structure and function of neural networks in the retina

1988 ◽  
Vol 46 ◽  
pp. 26-27
Author(s):  
Peter Sterling
Keyword(s):  
Ganglion Cells ◽  
Three Dimensional ◽  
Structure And Function ◽  
Synaptic Connections ◽  
Visual Axis ◽  
One Dimensional ◽  
Cat Retina ◽  
Ultrathin Sections ◽  
And Function ◽  
Insight Into

The synaptic connections in cat retina that link photoreceptors to ganglion cells have been analyzed quantitatively. Our approach has been to prepare serial, ultrathin sections and photograph en montage at low magnification (˜2000X) in the electron microscope. Six series, 100-300 sections long, have been prepared over the last decade. They derive from different cats but always from the same region of retina, about one degree from the center of the visual axis. The material has been analyzed by reconstructing adjacent neurons in each array and then identifying systematically the synaptic connections between arrays. Most reconstructions were done manually by tracing the outlines of processes in successive sections onto acetate sheets aligned on a cartoonist's jig. The tracings were then digitized, stacked by computer, and printed with the hidden lines removed. The results have provided rather than the usual one-dimensional account of pathways, a three-dimensional account of circuits. From this has emerged insight into the functional architecture.

Radiation Damage Studies with the HVEM

1972 ◽  
Vol 30 ◽  
pp. 680-681
Author(s):  
J. J. Laidler ◽  
B. Mastel
Keyword(s):  
Radiation Damage ◽  
Stainless Steels ◽  
Volume Expansion ◽  
Austenitic Stainless Steels ◽  
Test Facility ◽  
Fast Breeder Reactors ◽  
Breeder Reactors ◽  
Under Construction ◽  
Development Laboratory ◽  
Insight Into

One of the major materials problems encountered in the development of fast breeder reactors for commercial power generation is the phenomenon of swelling in core structural components and fuel cladding. This volume expansion, which is due to the retention of lattice vacancies by agglomeration into large polyhedral clusters (voids), may amount to ten percent or greater at goal fluences in some austenitic stainless steels. From a design standpoint, this is an undesirable situation, and it is necessary to obtain experimental confirmation that such excessive volume expansion will not occur in materials selected for core applications in the Fast Flux Test Facility, the prototypic LMFBR now under construction at the Hanford Engineering Development Laboratory (HEDL). The HEDL JEM-1000 1 MeV electron microscope is being used to provide an insight into trends of radiation damage accumulation in stainless steels, since it is possible to produce atom displacements at an accelerated rate with 1 MeV electrons, while the specimen is under continuous observation.

Failure Analysis With the Scanning Electron Microscope

1972 ◽  
Vol 30 ◽  
pp. 482-483
Author(s):  
John R. Devaney
Keyword(s):  
Electron Microscope ◽  
Scanning Electron Microscope ◽  
Integrated Circuits ◽  
Failure Analysis ◽  
High Reliability ◽  
Military Applications ◽  
Small Structure ◽  
Useful Life ◽  
Insight Into ◽  
Scanning Electron

Occasionally in history, an event may occur which has a profound influence on a technology. Such an event occurred when the scanning electron microscope became commercially available to industry in the mid 60's. Semiconductors were being increasingly used in high-reliability space and military applications both because of their small volume but, also, because of their inherent reliability. However, they did fail, both early in life and sometimes in middle or old age. Why they failed and how to prevent failure or prolong “useful life” was a worry which resulted in a blossoming of sophisticated failure analysis laboratories across the country. By 1966, the ability to build small structure integrated circuits was forging well ahead of techniques available to dissect and analyze these same failures. The arrival of the scanning electron microscope gave these analysts a new insight into failure mechanisms.

Study of the resistor material of an automotive spark plug by use of the charge-up effect along with elemental mapping in an electron microprobe

1991 ◽  
Vol 49 ◽  
pp. 742-743
Author(s):  
D. R. Liu ◽  
S. S. Shinozaki ◽  
J. S. Park ◽  
B. N. Juterbock
Keyword(s):  
Electron Microprobe ◽  
Present Report ◽  
Coated Sample ◽  
Valuable Insight ◽  
Elemental Mapping ◽  
Spark Plug ◽  
Carbon Coated ◽  
Electron Image ◽  
Electron Imaging ◽  
Insight Into

The electric and thermal properties of the resistor material in an automotive spark plug should be stable during its service lifetime. Containing many elements and many phases, this material has a very complex microstructure. Elemental mapping with an electron microprobe can reveal the distribution of all relevant elements throughout the sample. In this work, it is demonstrated that the charge-up effect, which would distort an electron image and, therefore, is normally to be avoided in an electron imaging work, could be used to advantage to reveal conductive and resistive zones in a sample. Its combination with elemental mapping can provide valuable insight into the underlying conductivity mechanism of the resistor.This work was performed in a CAMECA SX-50 microprobe. The spark plug used in the present report was a commercial product taken from the shelf. It was sectioned to expose the cross section of the resistor. The resistor was known not to contain the precious metal Au as checked on the carbon coated sample. The sample was then stripped of carbon coating and re-coated with Au.

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