scholarly journals Discovery of Cell Aggregate-Inducing Peptides

Processes ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 538
Author(s):  
Yudai Futaki ◽  
Ikumi Amimoto ◽  
Megumi Tanaka ◽  
Tomoki Ito ◽  
Yoshiaki Hirano
Keyword(s):  
3D Cell Culture ◽  
Basic Research ◽  
Physical Method ◽  
Cell Physiology ◽  
Cell Aggregate ◽  
Tissue Microenvironment ◽  
A Cell ◽  
Cell Aggregations ◽  
The Relationship ◽  
Cell Cell

Most cells within the human body interact with neighboring cells and extracellular matrix (ECM) components to establish a unique 3D organization. These cell–cell and cell–ECM interactions form a complex communication network of biochemical and mechanical signals critical for normal cell physiology. The behavior of cells in a 3D environment is fundamentally different from that of cells in monolayer culture. Aggregation can affect cell–cell interactions, being more representative of the normal tissue microenvironment. Therefore, 3D cell culture technologies have been developed. The general method for cell aggregate is a physical method; it is difficult to control the size and number of cell aggregates. In any case, no chemical method has been discovered yet, so a new method to solve these problems is needed. In this paper, we describe the induction of a cell aggregate of the newly discovered (Lys-Pro)12(KP24) peptide. Since it was revealed that KP24 had cell aggregate-inducing activity, its derivatives were molecularly designed to clarify the importance of the KP24 sequence. We report that cell aggregations were induced by KP24 to form aggregates of fibroblast cells. We evaluated KP24 derivative periodic peptides such as (Lys-Pro-Pro)8(KPP24) and (Lys-Lys-Pro)8(KKP24). The relationship between the structure of the peptide chain and the activity induced by the cell aggregations was investigated from the viewpoint of basic research and the biomedical engineering field.

Lysosome Targeting Chimeras (LYTACs) for the Degradation of Secreted and Membrane Proteins

2019 ◽  
Author(s):  
Steven Banik ◽  
Kayvon Pedram ◽  
Simon Wisnovsky ◽  
Nicholas Riley ◽  
Carolyn Bertozzi
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Membrane Proteins ◽  
Growth Factor Receptor ◽  
Basic Research ◽  
Biochemical Pathway ◽  
Programmed Death Ligand 1 ◽  
Programmed Death ◽  
A Cell ◽  
Epidermal Growth ◽  
Powerful Strategy

<p>Targeted protein degradation is a powerful strategy to address the canonically undruggable proteome. However, current technologies are limited to targets with cytosolically-accessible and ligandable domains. Here, we designed and synthesized conjugates capable of binding both a cell surface lysosome targeting receptor and the extracellular domain of a target protein. These lysosome targeting chimeras (LYTACs) consist of an antibody fused to agonist glycopeptide ligands for the cation-independent mannose-6-phosphate receptor (CI-M6PR). LYTACs enabled a CRISPRi knockdown screen revealing the biochemical pathway for CI-M6PR-mediated cargo internalization. We demonstrated that LYTACs mediate efficient degradation of Apolipoprotein-E4, epidermal growth factor receptor (EGFR), CD71, and programmed death-ligand 1 (PD-L1). LYTACs represent a modular strategy for directing secreted and membrane proteins for degradation in the context of both basic research and therapy. <b></b></p>

scholarly journals Individual quality of life and the environment – towards a concept of livable areas for persons with disabilities in Poland

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Izabela Grabowska ◽  
Radosław Antczak ◽  
Jan Zwierzchowski ◽  
Tomasz Panek
Keyword(s):  
Quality Of Life ◽  
Environmental Conditions ◽  
Basic Research ◽  
Research Problem ◽  
Individual Characteristics ◽  
Living Conditions ◽  
Special Focus ◽  
Persons With Disabilities ◽  
The Relationship

Abstract Background The United Nations Convention on the Rights of Persons with Disabilities [1] highlights the need to create proper socioeconomic and political conditions for persons with disabilities, with a special focus on their immediate living conditions. According to the Convention, these conditions should be built to ensure that persons with disabilities have the potential to enjoy a high quality of life (QoL), and this principle is reflected in the notion of livable areas. The crucial aspect of this framework is the relationship between the individual QoL and the environment, broadly understood as the socioeconomic as well as the technical conditions in which persons with disabilities function. Methods The basic research problem was to assess the relationship between individual QoL for the population with disabilities as a dependent variable and livability indicators as independent variables, controlling for individual characteristics. The study used a dataset from the EU-SILC (European Union Statistics on Income and Living Conditions) survey carried out in 2015 in Poland. The research concept involved several steps. First, we created a variable measuring the QoL for the entire population with disabilities. To measure the multidimensional QoL, we used Sen’s capability approach as a general concept, which was operationalized by the MIMIC (multiple indicators multiple causes) model. In the second step, we identified the livability indicators available in the official statistics, and merged them with survey data. Finally, in the last step, we ran the regression analysis. We also checked the data for the nested structure. Results We confirmed that the general environmental conditions, focused on creating livable areas, played a significant role in shaping the QoL of persons with disabilities; i.e., we found that the higher the level of the local Human Development Index, the higher the quality of life of the individuals living in this area. This relationship held even after controlling for the demographic characteristics of the respondents. Moreover, we found that in addition to the general environmental conditions, the conditions created especially for persons with disabilities (i.e., services for this group and support for their living conditions) affected the QoL of these individuals. Conclusions The results illustrate the need to strengthen policies aimed at promoting the QoL of persons with disabilities by creating access to community assets and services that can contribute to improving the life chances of this population.

scholarly journals DIAPH2, PTPRD and HIC1 Gene Polymorphisms and Laryngeal Cancer Risk

2021 ◽  
Vol 18 (14) ◽  
pp. 7486
Author(s):  
Mirosław Śnit ◽  
Maciej Misiołek ◽  
Wojciech Ścierski ◽  
Anna Koniewska ◽  
Grażyna Stryjewska-Makuch ◽  
...  
Keyword(s):  
Cancer Risk ◽  
Laryngeal Cancer ◽  
Basic Research ◽  
Control Groups ◽  
Allele Distribution ◽  
Study Results ◽  
Risk Patients ◽  
And Control ◽  
The Relationship

AIM, DIAPH2, PTPRD and HIC1 are the cell glycoprotein, which play an important role in the occurrence and development of tumors. This study was designed to assess the association between DIAPH2, PTPRD and HIC1 SNPs and laryngeal cancer risk. PATIENTS AND METHODS: This study including 267 patients with histologically confirmed laryngeal cancer and 157 controls. The relationship between genetic variations DIAPH2 (rs6620138), PTPRD (rs3765142) and HIC1 (rs9901806) and the onset of laryngeal cancer were investigated. Statistical analysis to calculate the relationship between DIAPH2, PTPRD and HIC1 genes polymorphism and pathogenesis of laryngeal cancer. RESULTS: The results showed that rs6620138 DIAPH2 polymorphism could increase the onset risk of laryngeal cancer. Statistically significant differences in allele distribution of rs6620138 DIAPH2 and rs9901806 HIC1 in the case and control groups subgroups. CONCLUSIONS: This study results suggested that genetic variation of rs6620138 DIAPH2 polymorphism is related to the susceptibility to laryngeal cancer. Our results provide a basis to begin basic research on the role of DIAPH2 gene in the pathogenesis of laryngeal cancer.

scholarly journals Relationship between NAFLD and Periodontal Disease from the View of Clinical and Basic Research, and Immunological Response

2021 ◽  
Vol 22 (7) ◽  
pp. 3728
Author(s):  
Masahiro Hatasa ◽  
Sumiko Yoshida ◽  
Hirokazu Takahashi ◽  
Kenichi Tanaka ◽  
Yoshihito Kubotsu ◽  
...  
Keyword(s):  
Risk Factor ◽  
Periodontal Disease ◽  
Alveolar Bone ◽  
Basic Research ◽  
Epidemiological Studies ◽  
Cross Sectional ◽  
Periodontopathic Bacteria ◽  
In Vivo Animal Model ◽  
The Relationship

Periodontal disease is an inflammatory disease caused by pathogenic oral microorganisms that leads to the destruction of alveolar bone and connective tissues around the teeth. Although many studies have shown that periodontal disease is a risk factor for systemic diseases, such as type 2 diabetes and cardiovascular diseases, the relationship between nonalcoholic fatty liver disease (NAFLD) and periodontal disease has not yet been clarified. Thus, the purpose of this review was to reveal the relationship between NAFLD and periodontal disease based on epidemiological studies, basic research, and immunology. Many cross-sectional and prospective epidemiological studies have indicated that periodontal disease is a risk factor for NAFLD. An in vivo animal model revealed that infection with periodontopathic bacteria accelerates the progression of NAFLD accompanied by enhanced steatosis. Moreover, the detection of periodontopathic bacteria in the liver may demonstrate that the bacteria have a direct impact on NAFLD. Furthermore, Porphyromonas gingivalis lipopolysaccharide induces inflammation and accumulation of intracellular lipids in hepatocytes. Th17 may be a key molecule for explaining the relationship between periodontal disease and NAFLD. In this review, we attempted to establish that oral health is essential for systemic health, especially in patients with NAFLD.

scholarly journals Experimental study of the interaction range and association rate of surface-attached cadherin 11

1998 ◽  
Vol 95 (16) ◽  
pp. 9256-9261 ◽  
Author(s):  
Anne Pierres ◽  
Hélène Feracci ◽  
Véronique Delmas ◽  
Anne-Marie Benoliel ◽  
Jean-Paul Thiery ◽  
...  
Keyword(s):  
Adhesion Molecules ◽  
Bond Formation ◽  
Slow Motion ◽  
Classical Type ◽  
Association Rate ◽  
Interaction Range ◽  
A Cell ◽  
Coated Surfaces ◽  
The Relationship

We describe a method allowing quantitative determination of the interaction range and association rate of individual surface-attached molecules. Spherical beads (1.4 μm radius) were coated with recombinant outer domains of the newly described classical type II cadherin 11, a cell adhesion molecule. Beads were driven along cadherin-coated surfaces with a hydrodynamic force of ≈1 pN, i.e., much less than the mechanical strength of many ligand-receptor bonds. Spheres displayed periods of slow motion interspersed with arrests of various duration. Particle position was monitored with 50 Hz frequency and 0.025 μm accuracy. Nearly 1 million positions were recorded and processed. Comparison between experimental and computer-simulated trajectories suggested that velocity fluctuations might be related quantitatively to Brownian motion perpendicular to the surface. The expected amplitude of this motion was of order of 100 nm. Theoretical analysis of the relationship between sphere acceleration and velocity allowed simultaneous determination of the wall shear rate and van der Waals attraction between spheres and surface. The Hamaker constant was estimated at 2.9 × 10−23 J. The frequency of bond formation was then determined as a function of sphere velocity. Experimental data were consistent with the view that the rate of association between a pair of adhesion molecules was ≈1.2 × 10−3 s−1 and the interaction range was ≈10 nm. It is concluded that the presented methodology allows sensitive measurement of sphere-to-surface interactions (with ≈10 fN sensitivity) as well as the effective range and rate of bond formation between individual adhesion molecules.

scholarly journals MICRURGICAL STUDIES IN CELL PHYSIOLOGY

1926 ◽  
Vol 10 (1) ◽  
pp. 9-21 ◽  
Author(s):  
Paul Reznikoff
Keyword(s):  
Heavy Metals ◽  
Metal Cation ◽  
Surface Membrane ◽  
The Other ◽  
Contractile Vacuole ◽  
Toxic Action ◽  
Cell Physiology ◽  
Relative Toxicity ◽  
A Cell

I. Plasmalemma. 1. The order of toxicity of the salts used in these experiments on the surface membrane of a cell, taking as a criterion viability of amebæ immersed in solutions for 1 day, is HgCl2, FeCl3&gt; AlCl3&gt; CuCl2&gt; PbCl2&gt; FeCl2. Using viability for 5 days as a criterion, the order of toxicity is PbCl2&gt; CuCl2&gt; HgCl2&gt; AlCl3&gt; FeCl3&gt; FeCl2. 2. The rate of toxicity is in the order FeCl3&gt; HgCl2&gt; AlCl3&gt; FeCl2&gt; CuCl2&gt; PbCl2. 3. The ability of amebæ to recover from a marked tear of the plasmalemma in the solutions of the salts occurred in the following order: AlCl3&gt; PbCl2&gt; FeCl2&gt; CuCl2&gt; FeCl3&gt; HgCl2. II. Internal Protoplasm. 4. The relative toxicity of the salts on the internal protoplasm, judged by the recovery of the amebæ from large injections and the range over which these salts can cause coagulation of the internal protoplasm, is in the following order: PbCl2&gt; CuCl2&gt; FeCl3&gt; HgCl2&gt; FeCl2&gt; AlCl3. 5. AlCl3 in concentrations between M/32 and M/250 causes a marked temporary enlargement of the contractile vacuole. FeCl2, FeCl3, and CuCl3 produce a slight enlargement of the vacuole. 6. PbCl2, in concentrations used in these experiments, appears to form a different type of combination with the internal protoplasm than do the other salts. III. Permeability. 7. Using the similarity in appearance of the internal protoplasm after injection and after immersion to indicate that the surface is permeable to a substance in which the ameba is immersed, it is concluded that AlCl3 can easily penetrate the intact plasmalemma. CuCl2 also seems to have some penetrating power. None of the other salts studied give visible internal evidence of penetrability into the ameba. IV. Toxicity. 8. The toxic action of the chlorides of the heavy metals used in these experiments, and of aluminum, is exerted principally upon the surface of the cell and is due not only to the action of the metal cation but also to acid which is produced by hydrolysis.

scholarly journals Repression of differentiation genes by Hes transcription factors fuels neural tumour growth in Drosophila

2021 ◽  
Author(s):  
Chrysanthi Voutyraki ◽  
Alexandros Choromidis ◽  
Vasiliki Theodorou ◽  
Christina Efraimoglou ◽  
Gerasimos Anagnostopoulos ◽  
...  
Keyword(s):  
Stem Cell ◽  
Transcription Factors ◽  
Notch Signaling ◽  
Tumour Growth ◽  
Metabolic Reprogramming ◽  
Cell Physiology ◽  
Malignant Tumours ◽  
Rna Profiling ◽  
A Cell

Background: Neural stem cells (NSC) in divide asymmetrically to generate a cell that retains stem cell identity and another that is routed to differentiation. Prolonged mitotic activity of the NSCs gives rise to the plethora of neurons and glial cells that wire the brain and nerve cord. Genetic insults, such as excess of Notch signaling, perturb the normal NSC proliferation programs and trigger the formation of NSC hyperplasias, that can later progress to malignancies. Hes proteins are crucial mediators of Notch signaling and in the NSC context they act by repressing a cohort of early pro-differentiation transcription factors. Downregulation of these pro-differentiation factors makes NSC progeny cells susceptible to adopting an aberrant stem cell program. We have recently shown that Hes overexpression in Drosophila leads to NSC hyperplasias that progress to malignant tumours after allografting to adult hosts. Methods: We have combined genetic analysis, tissue allografting and transcriptomic approaches to address the role of Hes genes in NSC malignant transformation. Results: We show that the E(spl) genes are important mediators in the progression of Notch hyperplasias to malignancy, since allografts lacking the E(spl) genes grow much slower. We further present RNA profiling of Hes-induced tumours at two different stages after allografting. We find that the same cohort of differentiation-promoting transcription factors that are repressed in the primary hyperplasias continue to be downregulated after transplantation. This is accompanied by an upregulation of stress-response genes and metabolic reprogramming. Conclusions: The combination of dedifferentiation and cell physiology changes most likely drive tumour growth.

Sign in / Sign up

Export Citation Format

Share Document