XIST RNA: a window into the broader role of RNA in nuclear chromosome architecture

XIST RNA triggers the transformation of an active X chromosome into a condensed, inactive Barr body and therefore provides a unique window into transitions of higher-order chromosome architecture. Despite recent progress, how XIST RNA localizes and interacts with the X chromosome remains poorly understood. Genetic engineering of XIST into a trisomic autosome demonstrates remarkable capacity of XIST RNA to localize and comprehensively silence that autosome. Thus, XIST does not require X chromosome-specific sequences but operates on mechanisms available genome-wide. Prior results suggested XIST localization is controlled by attachment to the insoluble nuclear scaffold. Our recent work affirms that scaffold attachment factor A (SAF-A) is involved in anchoring XIST, but argues against the view that SAF-A provides a unimolecular bridge between RNA and the chromosome. Rather, we suggest that a complex meshwork of architectural proteins interact with XIST RNA. Parallel work studying the territory of actively transcribed chromosomes suggests that repeat-rich RNA \u27coats\u27 euchromatin and may impact chromosome architecture in a manner opposite of XIST A model is discussed whereby RNA may not just recruit histone modifications, but more directly impact higher-order chromatin condensation via interaction with architectural proteins of the nucleus.This article is part of the themed issue \u27X-chromosome inactivation: a tribute to Mary Lyon\u27

Technology Utilization in the Field of School Counseling: An Action Research Study

The purpose of this study was to analyze how school counselors utilize technology in their school counseling programs and to generate methods for encouraging such use within the Georgia School Counselors Association. Several variables were examined in this study. The main variable examined was counselor use of technology. Counselor use of technology was defined as the type, frequency, and location of technology use by the counselor. Other variables that were examined that influence counselor adoption and use of technology included administrator support for technology use, funding to acquire technology, access to the technology, level of comfort using technology, college training for using technology in counseling, motivation to use technology, counselor willingness to participate in staff development, and school location - rural or urban. The participants of this study included 145 elementary, middle, and high school counselors from eleven states. The instruments used in the study assessed the counselors' frequency of technology use for clerical tasks, teacher training, parent training, individual counseling, group counseling, classroom guidance, communication, and Internet searches. The study discovered that school counselors are using technology for a variety of tasks from the mundane clerical tasks to innovative interactive lessons. In addition, it was concluded that school counselors are interested in staff development on technology if it can benefit their programs. Many participants involved in this research utilize technology in innovative ways. The innovative ideas discovered in this study have assisted me in designing professional development for GSCA, and other counselors, on innovative uses of technology

SAF-A mutants disrupt chromatin structure through dominant negative effects on RNAs associated with chromatin

Here we provide a brief review of relevant background before presenting results of our investigation into the interplay between scaffold attachment factor A (SAF-A), chromatin-associated RNAs, and DNA condensation. SAF-A, also termed heterogenous nuclear protein U (hnRNP U), is a ubiquitous nuclear scaffold protein that was implicated in XIST RNA localization to the inactive X-chromosome (Xi) but also reported to maintain open DNA packaging in euchromatin. Here we use several means to perturb SAF-A and examine potential impacts on the broad association of RNAs on euchromatin, and on chromatin compaction. SAF-A has an N-terminal DNA binding domain and C-terminal RNA binding domain, and a prominent model has been that the protein provides a single-molecule bridge between XIST RNA and chromatin. Here analysis of the impact of SAF-A on broad RNA-chromatin interactions indicate greater biological complexity. We focus on SAF-A\u27s role with repeat-rich C0T-1 hnRNA (repeat-rich heterogeneous nuclear RNA), shown recently to comprise mostly intronic sequences of pre-mRNAs and diverse long non-coding RNAs (lncRNAs). Our results show that SAF-A mutants cause dramatic changes to cytological chromatin condensation through dominant negative effects on C0T-1 RNA\u27s association with euchromatin, and likely other nuclear scaffold factors. In contrast, depletion of SAF-A by RNA interference (RNAi) had no discernible impact on C0T-1 RNA, nor did it cause similarly marked chromatin changes as did three different SAF-A mutations. Overall results support the concept that repeat-rich, chromatin-associated RNAs interact with multiple RNA binding proteins (RBPs) in a complex dynamic meshwork that is integral to larger-scale chromatin architecture and collectively influences cytological-scale DNA condensation

Algebraic Bethe ansatz for a quantum integrable derivative nonlinear Schrodinger model

We find that the quantum monodromy matrix associated with a derivative nonlinear Schrodinger (DNLS) model exhibits U(2) or U(1,1) symmetry depending on the sign of the related coupling constant. By using a variant of quantum inverse scattering method which is directly applicable to field theoretical models, we derive all possible commutation relations among the operator valued elements of such monodromy matrix. Thus, we obtain the commutation relation between creation and annihilation operators of quasi-particles associated with DNLS model and find out the $S$-matrix for two-body scattering. We also observe that, for some special values of the coupling constant, there exists an upper bound on the number of quasi-particles which can form a soliton state for the quantum DNLS model.Comment: 17 pages, Latex, minor typos corrected, to be published in Nucl. Phys.

Thermodynamics of Binding by Calmodulin Correlates with Target Peptide α-Helical Propensity

In this work, we have examined contributions to the thermodynamics of calmodulin (CaM) binding from the intrinsic propensity for target peptides to adopt an α-helical conformation. CaM target sequences are thought to commonly reside in disordered regions within proteins. Using the ability of TFE to induce α-helical structure as a proxy, the six peptides studied range from having almost no propensity to adopt α-helical structure through to a very high propensity. This despite all six peptides having similar CaM-binding affinities. Our data indicate there is some correlation between the deduced propensities and the thermodynamics of CaM binding. This finding implies that molecular recognition features, such as CaM target sequences, may possess a broad range of propensities to adopt local structure. Given that these peptides bind to CaM with similar affinities, the data suggest that having a higher propensity to adopt α-helical structure does not necessarily result in tighter binding, and that the mechanism of CaM binding is very dependent on the nature of the substrate sequence

Jost solutions and quantum conserved quantities of an integrable derivative nonlinear Schrodinger model

We study differential and integral relations for the quantum Jost solutions associated with an integrable derivative nonlinear Schrodinger (DNLS) model. By using commutation relations between such Jost solutions and the basic field operators of DNLS model, we explicitly construct first few quantum conserved quantities of this system including its Hamiltonian. It turns out that this quantum Hamiltonian has a new kind of coupling constant which is quite different from the classical one. This modified coupling constant plays a crucial role in our comparison between the results of algebraic and coordinate Bethe ansatz for the case of DNLS model. We also find out the range of modified coupling constant for which the quantum $N$-soliton state of DNLS model has a positive binding energy.Comment: 36 pages, latex, two references added, to be published in Nucl. Phys.

Graphical representation of the partition function for a 1-D delta-function Bose gas

One-dimensional repulsive delta-function bose system is studied. By only using the Bethe ansatz equation, n-particle partition functions are exactly calculated. From this expression for the n-particle partition function, the n-particle cluster integral is derived. The results completely agree with those of the thermal Bethe ansatz (TBA). This directly proves the validity of the TBA. The theory of partitions and graphs is used to simplify the discussion.Comment: 15 page

The quantum non-linear Schrodinger model with point-like defect

We establish a family of point-like impurities which preserve the quantum integrability of the non-linear Schrodinger model in 1+1 space-time dimensions. We briefly describe the construction of the exact second quantized solution of this model in terms of an appropriate reflection-transmission algebra. The basic physical properties of the solution, including the space-time symmetry of the bulk scattering matrix, are also discussed.Comment: Comments on the integrability and the impurity free limit adde

Structural basis for activation of calcineurin by calmodulin

The highly conserved phosphatase calcineurin plays vital roles in numerous processes including T-cell activation, development and function of the central nervous system, and cardiac growth. It is activated by the calcium sensor calmodulin. Calmodulin binds to a regulatory domain within calcineurin, causing a conformational change that displaces an autoinhibitory domain from the active site, resulting in activation of the phosphatase. This is the same general mechanism by which calmodulin activates calmodulin-dependent protein kinases. Previously published data has hinted that the regulatory domain of calcineurin is intrinsically disordered. In this work we demonstrate that the regulatory domain is unstructured and that it folds upon binding calmodulin, ousting the autoinhibitory domain from the catalytic site. The regulatory domain is 95 residues long, with the autoinhibitory domain attached to its C-terminal end and the 24 residue calmodulin binding region towards the N-terminal end. This is unlike the calmodulin-dependent protein kinases which have calmodulin binding sites and autoinhibitory domains immediately adjacent in sequence. Our data demonstrate that not only does the calmodulin binding region fold, but that an ~25-30 residue region between it and the autoinhibitory domain also folds, resulting in over half of the regulatory domain adopting α-helical structure. This appears to be the first observation of calmodulin inducing folding of this scale outside of its binding site on a target protein