scholarly journals Tuning up Transcription Factors for Therapy

Molecules ◽  
2020 ◽  
Vol 25 (8) ◽  
pp. 1902
Author(s):  
Attila Becskei
Keyword(s):  
Transcription Factors ◽  
Genetic Characterization ◽  
Dissociation Constants ◽  
Cancer Therapies ◽  
Transcription Activator ◽  
Range Interaction ◽  
Long Range Interaction ◽  
Recent Developments

The recent developments in the delivery and design of transcription factors put their therapeutic applications within reach, exemplified by cell replacement, cancer differentiation and T-cell based cancer therapies. The success of such applications depends on the efficacy and precision in the action of transcription factors. The biophysical and genetic characterization of the paradigmatic prokaryotic repressors, LacI and TetR and the designer transcription factors, transcription activator-like effector (TALE) and CRISPR-dCas9 revealed common principles behind their efficacy, which can aid the optimization of transcriptional activators and repressors. Further studies will be required to analyze the linkage between dissociation constants and enzymatic activity, the role of phase separation and squelching in activation and repression and the long-range interaction of transcription factors with epigenetic regulators in the context of the chromosomes. Understanding these mechanisms will help to tailor natural and synthetic transcription factors to the needs of specific applications.

scholarly journals Tuning up Transcription Factors for Therapy

2020 ◽  
Author(s):  
Attila Becskei
Keyword(s):  
Transcription Factors ◽  
Genetic Characterization ◽  
Dissociation Constants ◽  
Cancer Therapies ◽  
Range Interaction ◽  
Long Range Interaction ◽  
Recent Developments ◽  
Epigenetic Regulators

The recent developments in the delivery and design of transcription factors put their therapeutic applications within reach, exemplified by cell replacement, cancer differentiation and T-cell based cancer therapies. The success of such applications depends on the efficacy and precision in the action of transcription factors. The biophysical and genetic characterization of the paradigmatic prokaryotic repressors, LacI and TetR and the designer transcription factors, TALE and CRISPR-Cas9 revealed common rules, which can help the optimization of activators and repressors. Further studies will be required to analyze the linkage between dissociation constants and enzymatic activity, the role of phase separation and squelching in activation and repression, and the long-range interaction of transcription factors with epigenetic regulators in the context of the chromosomes. Understanding these mechanisms will help to tailor systematically optimized designer transcription factors to the needs of specific applications.

Biological and genetic characterization of the role of SRSF2 mutations in the pathogenesis of myelodysplastic syndromes

2015 ◽  
Vol 43 (9) ◽  
pp. S73
Author(s):  
Ayana Kon ◽  
Satoshi Yamazaki ◽  
Keisuke Kataoka ◽  
Tetsuichi Yoshizato ◽  
Yusuke Shiozawa ◽  
...  
Keyword(s):  
Myelodysplastic Syndromes ◽  
Genetic Characterization

scholarly journals Role of the INDETERMINATE DOMAIN Genes in Plants

2019 ◽  
Vol 20 (9) ◽  
pp. 2286 ◽  
Author(s):  
Manu Kumar ◽  
Dung Thi Le ◽  
Seongbin Hwang ◽  
Pil Joon Seo ◽  
Hyun Uk Kim
Keyword(s):  
Plant Architecture ◽  
Genetic Characterization ◽  
Sugar Metabolism ◽  
Hormone Signaling ◽  
Biological Functions ◽  
Transcription Factor Family ◽  
Physiological Processes ◽  
Ammonium Metabolism

The INDETERMINATE DOMAIN (IDD) genes comprise a conserved transcription factor family that regulates a variety of developmental and physiological processes in plants. Many recent studies have focused on the genetic characterization of IDD family members and revealed various biological functions, including modulation of sugar metabolism and floral transition, cold stress response, seed development, plant architecture, regulation of hormone signaling, and ammonium metabolism. In this review, we summarize the functions and working mechanisms of the IDD gene family in the regulatory network of metabolism and developmental processes.

scholarly journals Traumatic glioblastoma: commentary and suggested mechanism

2018 ◽  
Vol 46 (6) ◽  
pp. 2170-2176
Author(s):  
Nissim Ohana ◽  
Daniel Benharroch ◽  
Dimitri Sheinis ◽  
Abraham Cohen
Keyword(s):  
Traumatic Brain Injury ◽  
Transcription Factors ◽  
Brain Injury ◽  
Brain Injuries ◽  
Hypoxia Inducible Factor ◽  
Subsequent Development ◽  
Factors Associated ◽  
The Relationship

The role of head trauma in the development of glioblastoma is highly controversial and has been minimized since first put forward. This is not unexpected because skull injuries are overwhelmingly more common than glioblastoma. This paper presents a commentary based on the contributions of James Ewing, who established a major set of criteria for the recognition of an official relationship between trauma and cancer. Ewing’s criteria were very stringent. The scholars who succeeded Ewing have facilitated the characterization of traumatic brain injuries since the introduction of computed tomography and magnetic resonance imaging. Discussions of the various criteria that have since developed are now being conducted, and those of an unnecessarily limiting nature are being highlighted. Three transcription factors associated with traumatic brain injury have been identified: p53, hypoxia-inducible factor-1α, and c-MYC. A role for these three transcription factors in the relationship between traumatic brain injury and glioblastoma is suggested; this role may support a cause-and-effect link with the subsequent development of glioblastoma.

scholarly journals Why Are Viscosity and Nonlinearity Bound to Make an Impact in Clinical Elastographic Diagnosis?

Sensors ◽  
2020 ◽  
Vol 20 (8) ◽  
pp. 2379 ◽  
Author(s):  
Guillermo Rus ◽  
Inas H. Faris ◽  
Jorge Torres ◽  
Antonio Callejas ◽  
Juan Melchor
Keyword(s):  
Soft Tissues ◽  
Elastic Parameters ◽  
Tissue Microstructure ◽  
Non Invasive ◽  
Recent Developments ◽  
Mechanical Biomarkers ◽  
Nonlinear Elastic

The adoption of multiscale approaches by the biomechanical community has caused a major improvement in quality in the mechanical characterization of soft tissues. The recent developments in elastography techniques are enabling in vivo and non-invasive quantification of tissues’ mechanical properties. Elastic changes in a tissue are associated with a broad spectrum of pathologies, which stems from the tissue microstructure, histology and biochemistry. This knowledge is combined with research evidence to provide a powerful diagnostic range of highly prevalent pathologies, from birth and labor disorders (prematurity, induction failures, etc.), to solid tumors (e.g., prostate, cervix, breast, melanoma) and liver fibrosis, just to name a few. This review aims to elucidate the potential of viscous and nonlinear elastic parameters as conceivable diagnostic mechanical biomarkers. First, by providing an insight into the classic role of soft tissue microstructure in linear elasticity; secondly, by understanding how viscosity and nonlinearity could enhance the current diagnosis in elastography; and finally, by compounding preliminary investigations of those elastography parameters within different technologies. In conclusion, evidence of the diagnostic capability of elastic parameters beyond linear stiffness is gaining momentum as a result of the technological and imaging developments in the field of biomechanics.

scholarly journals Dynamic transcriptome and chromatin architecture in granulosa cells during chicken folliculogenesis

2022 ◽  
Vol 13 (1) ◽  
Author(s):  
Diyan Li ◽  
Chunyou Ning ◽  
Jiaman Zhang ◽  
Yujie Wang ◽  
Qianzi Tang ◽  
...  
Keyword(s):  
Granulosa Cells ◽  
Functional Characterization ◽  
Three Dimensional ◽  
Range Interaction ◽  
Ample Evidence ◽  
Chromatin Architecture ◽  
Complex Biological Process ◽  
Preovulatory Follicles ◽  
Long Range Interaction

AbstractFolliculogenesis is a complex biological process involving a central oocyte and its surrounding somatic cells. Three-dimensional chromatin architecture is an important transcription regulator; however, little is known about its dynamics and role in transcriptional regulation of granulosa cells during chicken folliculogenesis. We investigate the transcriptomic dynamics of chicken granulosa cells over ten follicular stages and assess the chromatin architecture dynamics and how it influences gene expression in granulosa cells at three key stages: the prehierarchical small white follicles, the first largest preovulatory follicles, and the postovulatory follicles. Our results demonstrate the consistency between the global reprogramming of chromatin architecture and the transcriptomic divergence during folliculogenesis, providing ample evidence for compartmentalization rearrangement, variable organization of topologically associating domains, and rewiring of the long-range interaction between promoter and enhancers. These results provide key insights into avian reproductive biology and provide a foundational dataset for the future in-depth functional characterization of granulosa cells.

Molecular mechanisms of iron uptake in eukaryotes

1996 ◽  
Vol 76 (1) ◽  
pp. 31-47 ◽  
Author(s):  
D. M. de Silva ◽  
C. C. Askwith ◽  
J. Kaplan
Keyword(s):  
Iron Uptake ◽  
Mammalian Cells ◽  
Iron Homeostasis ◽  
Molecular Mechanisms ◽  
Iron Acquisition ◽  
Genetic Disorders ◽  
Essential Element ◽  
Recent Developments

Iron serves essential functions in both prokaryotes and eukaryotes, and cells have highly specialized mechanisms for acquiring and handling this metal. The primary mechanism by which the concentration of iron in biologic systems is controlled is through the regulation of iron uptake. Although the role of transferrin in mammalian iron homeostasis has been well characterized, the study of genetic disorders of iron metabolism has revealed other, transferrin-independent, mechanisms by which cells can acquire iron. In an attempt to understand how eukaryotic systems take up this essential element, investigators have begun studying the simple eukaryote Saccharomyces cerevisiae. Several genes have been identified and cloned that act in concert to allow iron acquisition from the environment. Some of these genes appear to have functional homologues in human systems. This review focuses on the recent developments in understanding eukaryotic iron uptake with an emphasis on the genetic and molecular characterization of these systems in both cultured mammalian cells and S. cerevisiae. An unexpected connection between iron and copper homeostasis has been revealed by recent genetic studies, which confirm biologic observations made several decades ago.

scholarly journals Structural and Genetic Characterization of Glycosylation of Type a Flagellin in Pseudomonas aeruginosa

2004 ◽  
Vol 186 (9) ◽  
pp. 2523-2531 ◽  
Author(s):  
M. Schirm ◽  
S. K. Arora ◽  
A. Verma ◽  
E. Vinogradov ◽  
P. Thibault ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Gene Cluster ◽  
Genetic Characterization ◽  
Type A ◽  
Protein Backbone ◽  
Central Surface

ABSTRACT Type a flagellins from two strains of Pseudomonas aeruginosa, strains PAK and JJ692, were found to be glycosylated with unique glycan structures. In both cases, two sites of O-linked glycosylation were identified on each monomer, and these sites were localized to the central, surface-exposed domain of the monomer in the assembled filament. The PAK flagellin was modified with a heterogeneous glycan comprising up to 11 monosaccharide units that were O linked through a rhamnose residue to the protein backbone. The flagellin of JJ692 was less complex and had a single rhamnose substitution at each site. The role of the glycosylation island gene cluster in the production of each of these glycosyl moieties was investigated. These studies revealed that the orfA and orfN genes were required for attachment of the heterologous glycan and the proximal rhamnose residue, respectively.

Sign in / Sign up

Export Citation Format

Share Document