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"Delbrück, Max"
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Klf4 and Klf5 differentially inhibit mesoderm and endoderm differentiation in embryonic stem cells
Krüppel-like factors (Klf) 4 and 5 are two closely related members of the Klf family, known to play key roles in cell cycle regulation, somatic cell reprogramming and pluripotency. Here we focus on the functional divergence between Klf4 and Klf5 in the inhibition of mouse embryonic stem (ES) cell differentiation. Using microarrays and chromatin immunoprecipitation coupled to ultra-high-throughput DNA sequencing, we show that Klf4 negatively regulates the expression of endodermal markers in the undifferentiated ES cells, including transcription factors involved in the commitment of pluripotent stem cells to endoderm differentiation. Knockdown of Klf4 enhances differentiation towards visceral and definitive endoderm. In contrast, Klf5 negatively regulates the expression of mesodermal markers, some of which control commitment to the mesoderm lineage, and knockdown of Klf5 specifically enhances differentiation towards mesoderm. We conclude that Klf4 and Klf5 differentially inhibit mesoderm and endoderm differentiation in murine ES cells.
The Krüppel-like factors Klf4 and Klf5 have wide roles in cell biology including the regulation of pluripotency. In this study, Aksoy
et al
. demonstrate that Klf4 preferentially blocks the expression of endodermal markers in embryonic stem cells, whereas Klf5 negatively regulates mesodermal factors.
Journal Article
Touch receptor end-organ innervation and function require sensory neuron expression of the transcription factor Meis2
Touch sensation is primarily encoded by mechanoreceptors, called low-threshold mechanoreceptors (LTMRs), with their cell bodies in the dorsal root ganglia. Because of their great diversity in terms of molecular signature, terminal endings morphology, and electrophysiological properties, mirroring the complexity of tactile experience, LTMRs are a model of choice to study the molecular cues differentially controlling neuronal diversification. While the transcriptional codes that define different LTMR subtypes have been extensively studied, the molecular players that participate in their late maturation and in particular in the striking diversity of their end-organ morphological specialization are largely unknown. Here we identified the TALE homeodomain transcription factor Meis2 as a key regulator of LTMRs target-field innervation in mice. Meis2 is specifically expressed in cutaneous LTMRs, and its expression depends on target-derived signals. While LTMRs lacking Meis2 survived and are normally specified, their end-organ innervations, electrophysiological properties, and transcriptome are differentially and markedly affected, resulting in impaired sensory-evoked behavioral responses. These data establish Meis2 as a major transcriptional regulator controlling the orderly formation of sensory neurons innervating peripheral end organs required for light touch.
Journal Article
Metaproteomics Approach and Pathway Modulation in Obesity and Diabetes: A Narrative Review
Low-grade inflammatory diseases revealed metabolic perturbations that have been linked to various phenotypes, including gut microbiota dysbiosis. In the last decade, metaproteomics has been used to investigate protein composition profiles at specific steps and in specific healthy/pathologic conditions. We applied a rigorous protocol that relied on PRISMA guidelines and filtering criteria to obtain an exhaustive study selection that finally resulted in a group of 10 studies, based on metaproteomics and that aim at investigating obesity and diabetes. This batch of studies was used to discuss specific microbial and human metaproteome alterations and metabolic patterns in subjects affected by diabetes (T1D and T2D) and obesity. We provided the main up- and down-regulated protein patterns in the inspected pathologies. Despite the available results, the evident paucity of metaproteomic data is to be considered as a limiting factor in drawing objective considerations. To date, ad hoc prepared metaproteomic databases collecting pathologic data and related metadata, together with standardized analysis protocols, are required to increase our knowledge on these widespread pathologies.
Journal Article
Structure of the Arabidopsis RPM1 gene enabling dual specificity disease resistance
Plants can recognize pathogens through the action of disease resistance ( R ) genes, which confer resistance to pathogens expressing unique corresponding avirulence ( avr ) genes. The molecular basis of this gene-for-gene specificity is unknown. The Arabidopsis thaliana RPM1 gene enables dual specificity to pathogens expressing either of two unrelated Pseudomonas syringae avr genes. Despite this function, RPM1 encodes a protein sharing molecular features with recently described single-specificity R genes. Surprisingly, RPM1 is lacking from naturally occurring, disease-susceptible Arabidopsis accessions.
Journal Article
Creating a physical biology
In 1935 geneticist Nikolai Timoféeff-Ressovsky, radiation physicist Karl G. Zimmer, and quantum physicist Max Delbrück published \"On the Nature of Gene Mutation and Gene Structure,\" known subsequently as the \"Three-Man Paper.\" This seminal paper advanced work on the physical exploration of the structure of the gene through radiation physics and suggested ways in which physics could reveal definite information about gene structure, mutation, and action. Representing a new level of collaboration between physics and biology, it played an important role in the birth of the new field of molecular biology. The paper's results were popularized for a wide audience in the What is Life? lectures of physicist Erwin Schrödinger in 1944.
Despite its historical impact on the biological sciences, the paper has remained largely inaccessible because it was only published in a short-lived German periodical. Creating a Physical Biology makes the Three Man Paper available in English for the first time. Brandon Fogel's translation is accompanied by an introductory essay by Fogel and Phillip Sloan and a set of essays by leading historians and philosophers of biology that explore the context, contents, and subsequent influence of the paper, as well as its importance for the wider philosophical analysis of biological reductionism.
eBook
How Aristotle Discovered DNA
I am wondering how to address you, Viki, on this tremendous occasion, dedicated to commemorate your approaching “graduation from college”. Like many of us here assembled, you will have to think of a career to choose after this “graduation”. Perhaps the most appropriate form of address would be the way the young Goethe was instructed to address his grandfather, namely, “Erhabener Grosspapa!” That could be translated “Exalted Granddaddy”, but the flavor is not quite the same. I'll start out with some comments on Stan Ulam's talk. He invited us to speak up in the discussion to his talk, but I prefer to do it now when I have the floor to myself, so he can't talk back. There are several of his quotes that I want to comment on. One quote from Fermi on some theory that had been confirmed better than he, Fermi, thought the theory had any business of being that good. To anybody that works in biology and is aware of the fact that our brain evolved to help us get along in the cave, it is utterly miraculous and completely incomprehensible that this brain is capable of doing science at the success rate at which it is doing it. This is an aspect that mathematicians and physicists and most scientists tend to ignore. But it is one that is very much in the minds of those who are trying to understand more deeply the nature of our perceptive and cognitive capabilities from the point of view of biology…
Reference
GTP-binding proteins in plants
GTP-binding proteins are found in all organisms. They are important switches that cycle between an active and an inactive state, ensuring vectorial flow of information on the expense of guanosine triphosphate (GTP). In this review, we discuss current progress in the molecular characterization and functional analysis of plant genes encoding heterotrimeric and small GTPases. An up-to-date list including all cloned plant GTPase genes is given and a systematic classification is proposed.
Journal Article
Interference between two specific pathogen recognition events mediated by distinct plant disease resistance genes
We demonstrate that the interaction of the avirulence gene avrRpt2 and the cognate resistance gene RPS2 interferes with the interaction of avrRpm1-RPM1 in Arabidopsis. Interference is mediated outside of the bacterial pathogen Pseudomonas syringae, presumably at the level of recognition of avr-dependent signals, yet does not require the wild-type RPS2 product. A numerical excess of P. syringae expressing avrRpm1 can overcome this interference in mixed inoculations. The interference of avrRpt2-RPS2 engagement with RPM1-dependent functions is mirrored by transcriptional activation of genes preferentially expressed during RPM1- or RPS2-mediated disease resistance reactions. This demonstration of interference between two plant disease resistance genes suggests that their products compete for a common element(s) in a signal transduction pathway leading to disease resistance
Journal Article
