72 research outputs found
BRAHMA ATPase of the SWI/SNF Chromatin Remodeling Complex Acts as a Positive Regulator of Gibberellin-Mediated Responses in Arabidopsis
SWI/SNF chromatin remodeling complexes perform a pivotal function in the regulation of eukaryotic gene expression. Arabidopsis (Arabidopsis thaliana) mutants in major SWI/SNF subunits display embryo-lethal or dwarf phenotypes, indicating their critical role in molecular pathways controlling development and growth. As gibberellins (GA) are major positive regulators of plant growth, we wanted to establish whether there is a link between SWI/SNF and GA signaling in Arabidopsis. This study revealed that in brm-1 plants, depleted in SWI/SNF BRAHMA (BRM) ATPase, a number of GA-related phenotypic traits are GA-sensitive and that the loss of BRM results in markedly decreased level of endogenous bioactive GA. Transcriptional profiling of brm-1 and the GA biosynthesis mutant ga1-3, as well as the ga1-3/brm-1 double mutant demonstrated that BRM affects the expression of a large set of GA-responsive genes including genes responsible for GA biosynthesis and signaling. Furthermore, we found that BRM acts as an activator and directly associates with promoters of GA3ox1, a GA biosynthetic gene, and SCL3, implicated in positive regulation of the GA pathway. Many GA-responsive gene expression alterations in the brm-1 mutant are likely due to depleted levels of active GAs. However, the analysis of genetic interactions between BRM and the DELLA GA pathway repressors, revealed that BRM also acts on GA-responsive genes independently of its effect on GA level. Given the central position occupied by SWI/SNF complexes within regulatory networks controlling fundamental biological processes, the identification of diverse functional intersections of BRM with GA-dependent processes in this study suggests a role for SWI/SNF in facilitating crosstalk between GA-mediated regulation and other cellular pathways
Large scale physiological readjustment during growth enables rapid, comprehensive and inexpensive systems analysis
Abstract Background Rapidly characterizing the operational interrelationships among all genes in a given organism is a critical bottleneck to significantly advancing our understanding of thousands of newly sequenced microbial and eukaryotic species. While evolving technologies for global profiling of transcripts, proteins, and metabolites are making it possible to comprehensively survey cellular physiology in newly sequenced organisms, these experimental techniques have not kept pace with sequencing efforts. Compounding these technological challenges is the fact that individual experiments typically only stimulate relatively small-scale cellular responses, thus requiring numerous expensive experiments to survey the operational relationships among nearly all genetic elements. Therefore, a relatively quick and inexpensive strategy for observing changes in large fractions of the genetic elements is highly desirable. Results We have discovered in the model organism Halobacterium salinarum NRC-1 that batch culturing in complex medium stimulates meaningful changes in the expression of approximately two thirds of all genes. While the majority of these changes occur during transition from rapid exponential growth to the stationary phase, several transient physiological states were detected beyond what has been previously observed. In sum, integrated analysis of transcript and metabolite changes has helped uncover growth phase-associated physiologies, operational interrelationships among two thirds of all genes, specialized functions for gene family members, waves of transcription factor activities, and growth phase associated cell morphology control. Conclusions Simple laboratory culturing in complex medium can be enormously informative regarding the activities of and interrelationships among a large fraction of all genes in an organism. This also yields important baseline physiological context for designing specific perturbation experiments at different phases of growth. The integration of such growth and perturbation studies with measurements of associated environmental factor changes is a practical and economical route for the elucidation of comprehensive systems-level models of biological systems
Mast Cell Diseases in Practice and Research: Issues and Perspectives Raised by Patients and Their Recommendations to the Scientific Community and Beyond
Background: Since 2010, patients and physicians have collaborated to understand unmet needs of patients with mast cell diseases, incorporating mastocytosis and mast cell activation disorders, which include mast cell activation syndromes. Objective: This Open Innovation in Science project aims to expand understanding of the needs of patients affected by mast cell diseases, and encourage global communication among patient advocacy groups, physicians, researchers, industry, and government. A major aim is to support the scientific community's efforts to improve diagnosis, management, therapy, and patientsâ quality of life by addressing unmet needs. Methods: In collaboration with mast cell disease specialists, 13 patient advocacy groups from 12 countries and regions developed lists of top patient needs. A core team of leaders from patient advocacy groups collected and analyzed the data and proposed possible actions to address patient needs. Results: Findings identified similarities and differences among participating countries in unmet needs between patients with mastocytosis and those with mast cell activation syndromes. Issues emphasized struggles relating to the nature and rarity of mast cell diseases, their impact on quality of life, the diagnostic process, access to appropriate care, more effective treatment, and the need for research. Conclusions: Solutions vary across countries because situations differ, in particular regarding the existence of and access to centers of excellence and reference centers. Multifaceted mast cell activation syndrome barriers necessitate innovative approaches to improve access to appropriate care. The outcomes of this project should greatly support scientists and clinicians in their efforts to improve diagnosis, management, and treatment of patients with mastocytosis and mast cell activation disorders.The authors thank Tania Bray, Jan Hempstead, Heather
Mayne, Joanne Mulder-Brambleby, and Irene Wilson for their
supporting contributions, and all patients and families affected
by MCDs, who shared their needs and concerns for development
of this project. Authors involved in study conception and design
were P. Valent, S.V. Jennings, C.C. Finnerty, J.S. Hobart, M.
MartĂn-MartĂnez, K.A. Sinclair, V.M. Slee, J. Agopian, C. Akin,
I. Ălvarez-Twose, P. Bonadonna, A.A. Bowman, K. Brockow, H.
Bumbea, C. de Haro, J.S. Fok, K. Hartmann, N. Hegmann, O.
Hermine, M. Kalisiak, C.H. Katelaris, J. Kurz, P. Marcis, D.
Mayne, D. Mendoza, A. Moussy, G. Mudretzkyj, N. Nidelea
Vaia, M. Niedoszytko, H. Oude Elberink, A. Orfao, D.H.
Radia, S. Rosenmeier, E. Ribada, W. Schinhofen, J. Schwaab, F.
Siebenhaar, M. Triggiani, G. Tripodo, R. Velazquez, Y. Wielink,
F. Wimazal, T. Yigit, and C. Zubrinich. Authors involved in acquisition and review of data were S.V. Jennings, C.C. Finnerty,
J.S. Hobart, M. MartĂn-MartĂnez, K.A. Sinclair, V.M. Slee, J.
Agopian, C. Akin, I. Ălvarez-Twose, P. Bonadonna, A.A.
Bowman, K. Brockow, H. Bumbea, C. de Haro, J.S. Fok, K.
Hartmann, N. Hegmann, O. Hermine, M. Kalisiak, C.H.
Katelaris, J. Kurz, P. Marcis, D. Mayne, D. Mendoza, A.
Moussy, G. Mudretzkyj, N. Nidelea Vaia, M. Niedoszytko, H.
Oude Elberink, A. Orfao, D.H. Radia, S. Rosenmeier, E. Ribada, W. Schinhofen, J. Schwaab, F. Siebenhaar, M. Triggiani, G.
Tripodo, R. Velazquez, Y. Wielink, F. Wimazal, T. Yigit, C.
Zubrinich, and P. Valent. The Core Group (analysis and interpretation of data and drafting of the manuscript) include S.V.
Jennings, C.C. Finnerty, J.S. Hobart, M. MartĂn-MartĂnez, K.A.
Sinclair, and V.M. Slee. Critical revision was performed by S.V.
Jennings, C.C. Finnerty, J.S. Hobart, M. MartĂn-MartĂnez, K.A.
Sinclair, V.M. Slee, J. Agopian, C. Akin, I. Ălvarez-Twose, P.
Bonadonna, A.A. Bowman, K. Brockow, H. Bumbea, C. de
Haro, J.S. Fok, K. Hartmann, N. Hegmann, O. Hermine, M.
Kalisiak, C.H. Katelaris, J. Kurz, P. Marcis, D. Mayne, D.
Mendoza, A. Moussy, G. Mudretzkyj, N. Nidelea Vaia, M.
Niedoszytko, H. Oude Elberink, A. Orfao, D.H. Radia, S.
Rosenmeier, E. Ribada, W. Schinhofen, J. Schwaab, F. Siebenhaar, M. Triggiani, G. Tripodo, R. Velazquez, Y. Wielink, F Wimazal, T. Yigit, C. Zubrinich, and P. Valent
Mast Cell Diseases in Practice and Research:Issues and Perspectives Raised by Patients and Their Recommendations to the Scientific Community and Beyond
Background: Since 2010, patients and physicians have collaborated to understand unmet needs of patients with mast cell diseases, incorporating mastocytosis and mast cell activation disorders, which include mast cell activation syndromes. Objective: This Open Innovation in Science project aims to expand understanding of the needs of patients affected by mast cell diseases, and encourage global communication among patient advocacy groups, physicians, researchers, industry, and government. A major aim is to support the scientific community's efforts to improve diagnosis, management, therapy, and patientsâ quality of life by addressing unmet needs. Methods: In collaboration with mast cell disease specialists, 13 patient advocacy groups from 12 countries and regions developed lists of top patient needs. A core team of leaders from patient advocacy groups collected and analyzed the data and proposed possible actions to address patient needs. Results: Findings identified similarities and differences among participating countries in unmet needs between patients with mastocytosis and those with mast cell activation syndromes. Issues emphasized struggles relating to the nature and rarity of mast cell diseases, their impact on quality of life, the diagnostic process, access to appropriate care, more effective treatment, and the need for research. Conclusions: Solutions vary across countries because situations differ, in particular regarding the existence of and access to centers of excellence and reference centers. Multifaceted mast cell activation syndrome barriers necessitate innovative approaches to improve access to appropriate care. The outcomes of this project should greatly support scientists and clinicians in their efforts to improve diagnosis, management, and treatment of patients with mastocytosis and mast cell activation disorders
Rapid Sampling of Molecular Motions with Prior Information Constraints
Proteins are active, flexible machines that perform a range of different
functions. Innovative experimental approaches may now provide limited partial
information about conformational changes along motion pathways of proteins.
There is therefore a need for computational approaches that can efficiently
incorporate prior information into motion prediction schemes. In this paper, we
present PathRover, a general setup designed for the integration
of prior information into the motion planning algorithm of rapidly exploring
random trees (RRT). Each suggested motion pathway comprises a sequence of
low-energy clash-free conformations that satisfy an arbitrary number of prior
information constraints. These constraints can be derived from experimental data
or from expert intuition about the motion. The incorporation of prior
information is very straightforward and significantly narrows down the vast
search in the typically high-dimensional conformational space, leading to
dramatic reduction in running time. To allow the use of state-of-the-art energy
functions and conformational sampling, we have integrated this framework into
Rosetta, an accurate protocol for diverse types of structural modeling. The
suggested framework can serve as an effective complementary tool for molecular
dynamics, Normal Mode Analysis, and other prevalent techniques for predicting
motion in proteins. We applied our framework to three different model systems.
We show that a limited set of experimentally motivated constraints may
effectively bias the simulations toward diverse predicates in an outright
fashion, from distance constraints to enforcement of loop closure. In
particular, our analysis sheds light on mechanisms of protein domain swapping
and on the role of different residues in the motion
A Computational Framework for Proteome-Wide Pursuit and Prediction of Metalloproteins using ICP-MS and MS/MS Data
Effects of supervised aerobic and strength training in overweight and grade I obese pregnant women on maternal and foetal health markers: the GESTAFIT randomized controlled trial
Organizacja i kierownictwo Instytutu Badawczego LeĹnictwa w Warszawie (wg stanu na 1 I 1983 r.)
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