Unique Interaction Pattern Research Articles

A unique coplanar multi-center bonding network in doubly acetylide-bridged binuclear zirconocene complexes: A density functional theory study

A unique π-conjugative interaction pattern was experimentally revealed in the doubly acetylide-bridged binuclear group 4 metallocene complexes, which was involved in C–C coupling/cleavage reactions of acetylides and σ-alkynyl migrations. To elucidate how this multi-center bonding network affects the structural and reaction properties of these complexes, density functional theory (DFT) calculations and molecular orbital (MO) analysis were carried out on the electronic structure and σ-alkynyl migration mechanisms of the doubly acetylide-bridged binuclear Zr complexes, (L 2Zr) 2(μ-C CH) 2 (L = Cp, Cl). The B3LYP calculations suggested that the doubly [σ,π] acetylide-bridged complex C 2 h -(L 2Zr) 2(μ-C CH) 2 was produced by the reaction of L 2Zr(C CH) 2 with L 2Zr through a C 2 v -(L 2Zr) 2(μ-C CH) 2 intermediate followed by an isomerization process. In particular, the isomerization of C 2 h - or C 2 v -(L 2Zr) 2(μ-C CH) 2 is almost thermoneutral through a low barrier of 15.3–17.0 kcal/mol. The MO Walsh diagram revealed that the two isomers have a very similar six-center-six-electron bonding network. The coplanar π-conjunctive interaction by the electron donating and back-donating interactions between the metal centers and acetylide ligands significantly stabilizes the doubly acetylide-bridged binuclear group 4 metallocene complexes and the isomerization transition state.

RalA-exocyst-dependent Recycling Endosome Trafficking Is Required for the Completion of Cytokinesis

In eukaryotic cells, recycling endosome-mediated trafficking contributes to the completion of cytokinesis, in a manner under the control of the centrosome. We report that the exocyst complex and its interacting GTPase RalA play a critical role in this polarized trafficking process. RalA resides in the recycling endosome and relocates from the pericentrosomal region to key cytokinetic structures including the cleavage furrow, and later, the abscission site. This event is coupled to the dynamic redistribution of the exocyst proteins. These associate with the centrosome in interphase and concentrate on the central spindle/midbody during cytokinesis. Disruption of RalA-exocyst function leads to cytokinesis failure in late stages, particularly abscission, resembling the cytokinesis defects induced by loss of centrosome function. These data suggest that RalA and the exocyst may regulate vesicle delivery to the centrosome-related abscission site during the terminal stage of cytokinesis, implicating RalA as a critical regulator of cell cycle progression.

An Orally Active Selective Androgen Receptor Modulator Is Efficacious on Bone, Muscle, and Sex Function with Reduced Impact on Prostate

A number of conditions, including osteoporosis, frailty, and sexual dysfunction in both men and women have been improved using androgens. However, androgens are not widely used for these indications because of the side effects associated with these drugs. We describe an androgen receptor (AR) ligand that maintains expected anabolic activities with substantially diminished activity in the prostate. LGD2226 is a nonsteroidal, nonaromatizable, highly selective ligand for the AR, exhibiting virtually no affinity for the other intracellular receptors. We determined that AR bound to LGD2226 exhibits a unique pattern of protein-protein interactions compared with testosterone, fluoxymesterone (an orally available steroidal androgen), and other steroids, suggesting that LGD2226 alters the conformation of the ligand-binding domain. We demonstrated that LGD2226 is fully active in cell-based models of bone and muscle. LGD2226 exhibited anabolic activity on muscle and bone with reduced impact on prostate growth in rodent models. Biomechanical testing of bones from animals treated with LGD2226 showed strong enhancement of bone strength above sham levels. LGD2226 was also efficacious in a sex-behavior model in male rats measuring mounts, intromissions, ejaculations, and copulation efficiency. These results with an orally available, nonaromatizable androgen demonstrate the important role of the AR and androgens in mediating a number of beneficial effects in bone, muscle, and sexual function independent from the conversion of androgens into estrogenic ligands. Taken together, these results suggest that orally active, nonsteroidal selective androgen receptor modulators may be useful therapeutics for enhancing muscle, bone, and sexual function.

Interactions among genomic structure, function, and evolution revealed by comprehensive analysis of the Arabidopsis thaliana genome

The genome in a higher organism consists of a number of types of nucleotide sequence-specialized components, with each having tens of thousands of members or elements. It is crucial for our understanding of how a genome as an entity is organized, functions, and evolves to determine how these components are organized in the genome and how they relate with each other; however, no such knowledge is available. Here, we report a comprehensive analysis of the organization and interaction of all 40 components constituting the genome of the plant model species, Arabidopsis thaliana, at the whole-genome and chromosome levels. The 40 components include (i) 6 genome structural components consisting of GC%, genes, retrotransposons, DNA transposons, simple repeats, and low complex repeats; (ii) 3 evolutionarily critical features consisting of recombination rate, nucleotide substitutions, and nucleotide insertions/deletions; and (iii) 31 categories of genes with different functions and numbers of functions. We show that the distributions of 39 of the 40 components of the genome (excepting GC%) deviate significantly from the random distribution model and different types of the genome components are significantly correlated. These results remained to be true even when the genomic regions, such as centromeric regions, where transposable and repeat elements are abundant were excluded from the analyses. These findings suggest that DNA molecules contained in the Arabidopsis genome are each organized and structured from their constituting components in an unambiguous manner and that different types of the components that constitute or characterize the genome interact. The analysis also showed that each chromosome consists of a similar set of the components at similar densities, suggesting that the unique organization and interaction pattern of the components in each chromosome may represent, at least in part, the identity of a chromosome or a genome at the genome level, thus partly accounting for the phenotypic variation among different species. The data also provide comprehensive and new insights into many phenomena significant in genome biology, with which we particularly discuss the variation of genetic recombination. The variation of genetic recombination rate along a chromosomal arm is shaped, not only by the distribution of simple repeats, retrotransposons, DNA transposons, and nucleotide substitutions, but also by the functions of genes contained, especially those with multiple functions, suggesting that variation of genetic recombination along a chromosomal arm is the result of interactions among the components constituting local genome structure, function, and evolution.

Mitochondria primed by death signals determine cellular addiction to antiapoptotic BCL-2 family members

We show that the antiapoptotic proteins BCL-2, BCL-XL, MCL-1, BFL-1, and BCL-w each bear a unique pattern of interaction with a panel of peptides derived from BH3 domains of BH3-only proteins. Cellular dependence on an antiapoptotic protein for survival can be decoded based on the pattern of mitochondrial sensitivity to this peptide panel, a strategy that we call BH3 profiling. Dependence on antiapoptotic proteins correlates with sequestration of activator BH3-only proteins like BID or BIM by antiapoptotic proteins. Sensitivity to the cell-permeable BCL-2 antagonist ABT-737 is also related to priming of BCL-2 by activator BH3-only molecules. Our data allow us to distinguish a cellular state we call "primed for death," which can be determined by BH3 profiling and which correlates with dependence on antiapoptotic family members for survival.

On Analytic Process

An innovative methodology is presented for identifying and assessing change process in psychoanalytic treatments. Using the Psychotherapy Process Q-set (PQS), a panel of experienced psychoanalysts developed a prototype of an ideal psychoanalytic hour. This prototype was then applied to verbatim transcripts of three archived treatment samples: psychoanalyses, long-term analytic therapies, and brief psychodynamic therapies. The degree to which these treatments fostered an analytic process as represented by the prototype was measured quantitatively. Analytic process was significantly more present in psychoanalyses than in the long-term analytic therapies, which, in turn fostered significantly more analytic process than did brief psychodynamic therapies. The study demonstrates that, given descriptive language that does not represent a particular theoretical perspective, analysts can agree on a definition of analytic process, and that analytic process can be operationalized and quantitatively assessed. A second study demonstrates that despite consensus on its definition, there is not just one proper analytic process; rather, there are change processes unique to each dyad. Two quantitative case studies illustrate how each analytic pair has a unique interaction pattern linked to treatment progress. These dyad-unique "interaction structures" are recurrent, mutually influencing patterns of interaction, the experience, recognition, and comprehension of which appear to be a fundamental component of therapeutic action. A bipersonal model is described that attempts to bridge theories of therapeutic action that focus on insight and self-understanding and those that emphasize the patient's experience of the therapist.

Groundwater and human development: challenges and opportunities in livelihoods and environment

At less than 1000 km3/year, the world's annual use of groundwater is 1.5% of renewable water resource but contributes a lion's share of water-induced human welfare. Global groundwater use however has increased manifold in the past 50 years; and the human race has never had to manage groundwater use on such a large scale. Sustaining the massive welfare gains groundwater development has created without ruining the resource is a key water challenge facing the world today. In exploring this challenge, we have focused a good deal on conditions of resource occurrence but less so on resource use. I offer a typology of five groundwater demand systems as Groundwater Socio-ecologies (GwSE), each embodying a unique pattern of interactions between socio-economic and ecological variables, and each facing a distinct groundwater governance challenge. During the past century, a growing corpus of experiential knowledge has accumulated in the industrialized world on managing groundwater in various uses and contexts. A daunting global groundwater issue today is to apply this knowledge intelligently to by far the more formidable challenge that has arisen in developing regions of Asia and Africa, where groundwater irrigation has evolved into a colossal anarchy supporting billions of livelihoods but threatening the resource itself.

Bcl-2 and porin follow different pathways of TOM-dependent insertion into the mitochondrial outer membrane.

The bcl-2 gene encodes a 26kDa protein which functions as a central regulator of apoptosis. Here we investigated the pathway of Bcl-2alpha into the mitochondrial outer membrane using the yeast Saccharomyces cerevisiae as a model organism. We found that interactions of Bcl-2alpha with the mitochondrial import receptor Tom20 are dependent on two positively charged lysine residues in the immediate vicinity of the carboxy-terminal hydrophobic membrane anchor. The targeting function of these residues is independent of Tom22. Subsequent insertion of Bcl-2alpha into the mitochondrial outer membrane does not require Tom5 or Tom40, indicating that Bcl-2alpha bypasses the general import pore (GIP). Bcl-2alpha shows a unique pattern of interactions with the components of the mitochondrial TOM complex, demonstrating that at least two different pathways lead from the import receptor Tom20 into the mitochondrial outer membrane.

The eClassroom used as a Teacher's Training Laboratory to Measure the Impact of Group Facilitation on Attending, Participation, Interaction, and Involvement.

<P class=abstract>This paper describes and quantifies the role of group facilitation in an experiential, real-time, online, university level credit course entitled eAHSC/230 Interpersonal Communications and Relations. A new and unique group interaction pattern called parallel communication, as well as classical elements of group interaction are described and quantified. New measures of online group facilitation attributes with analogous face-to-face (F2F) counterparts are presented. Specifically, the impact of effective group facilitation on Attentiveness, on Interaction, on Involvement, and on Participation is explored. The paper also examines the eClassrom’s potential effectiveness as a real time teaching and training laboratory which also functions as a process observation tool that collects and feeds back interaction data, providing teachers and trainers immediate and ongoing measures of facilitation effectiveness.</P>

Sequential interactions in the marital communication of depressed men and women.

Despite studies showing patterns of sequential interaction between depressed wives and their husbands, no published research has contrasted sequential interactions of depressed husbands and their wives. This study compared problem-solving interactions of 49 couples with a depressed husband, 41 with a depressed wife, and 50 normal controls. Interactions were coded using the Marital Interaction Coding System. Although no clear patterns of sequential interaction distinguished couples with a depressed wife from normal control couples, results suggested a unique pattern of interaction between depressed husbands and their spouses, whereby positive communications from the husband resulted in decreased positivity and increased negativity from their wives. Given the importance of positivity for promoting effective problem solving, this pattern appears to have important implications for couples' long-term marital satisfaction and husbands' mood regulation.

The Utopian Pursuit of Death

The Utopian Pursuit of Death Siamak Movahedi Sometime ago, I came across a collection of notes that a Middle Eastern freelance writer had been compiling to edit as an anthology of the human experience of war. These notes were all final letters or wills and testaments of some militant men who had volunteered for dangerous or suicidal missions. These missions involved various regional conflicts in the Middle East between 1980 and 1990. The letters were either sent by the volunteers to their families right before a dangerous mission that took their life or were found in their possession when they later discovered their bodies. The war anthology never took form. A severe depression of the writer hampered the completion of the work. He later committed suicide. Within limits set by confidentiality, I was permitted to study the letters. 1 I thought I might have stumbled over some symbolically significant psychoanalytic texts. A communication that a person makes while he or she is anticipating an impending death is an overloaded message. It may be comparable to the first or the last dream in psychoanalysis. It may provide important clues not only to the person’s immediate psychic experience—needs, feelings, or images—but also to one’s characteristic mode of encounter with the object world. Although one cannot speak of a writer separate from his or her linguistic and cultural forms of self expression, differences in the pattern of such expressions should reveal something about the writer’s own psychic voice. For this analysis, I tried to bracket off the notes from external data as much as possible to see whether I could detect any pattern that I could attribute to the individual’s characteristic state of mind. This was not to underestimate the importance of the sociocultural context for the intelligibility of human action. Rather, I wished to focus primarily on a written piece of work to see how much we could legitimately trace to the writer’s psychic dispositions. [End Page 1] A writer does more than just describe things, make contact or express his or her feelings and desires. Somewhere in that description or contact the writer presents a self. The self resides in the projected consciousness of the object. The internal representation of the object is not separate from that of the self. Reading, listening, observing, and understanding are all forms of contextual interpretations. A pure phenomenological method is an illusion. We need instructions to observe and understand. A theory serves exactly that function. My focus being the inner dialogues of individuals, rather than the social institutions that structure them, I tried to conduct a psychoanalytic reading of the notes. That is, I tried to read them as though they were clinical process notes, and “listen” to layers of “messages” through a psychoanalytic “ear.” Just as in the analytic situation, my intention was to be able to feel myself into the writer’s self-experience to pick up his dominant affects, identify his wishes, defenses, unearth his inner representations of self and other, and depict his world view. For an observational instruction or conceptual lens, I relied on certain formulations of the object relation theory. Works of Bateson (1968) on communication and Shneidman (1993) on suicide notes served as my magnifying glasses. I began with the assumption that unconscious object relation fantasies structure the person’s attitudes and expectancies about the external world. Contact with the world, as articulated in one’s writings, should reflect such attitudes and expectancies. Within the same social-cultural environment, people display a unique pattern of interaction with one another and with things. Through the medium of social-cultural patterns people also express their own characteristic syntax of object relations. A letter exhibits an object relation event, a communication episode. It represents a ritual of engagement with an audience, a manifestation of a wish for relatedness, an attempt to contact a symbolic world. A letter, as with any other mode of communication, carries what Bateson (1968) terms a “report” and a “command.” The report component of a message, or its content, conveys information about the external world. The [End Page 2] command aspect, on the other hand, addresses the particular relationship between...

Characterization of the specificity of peptide binding to four DR haplotypes.

This study describes the establishment of a peptide-binding assay for purified, detergent-solubilized DR molecules. For each of the DR specificities and peptides studied, a unique pattern of interaction was observed. Excellent correlation was detected between the DR1-, 2-, 5-, and 52a-binding capacities and the known DR restrictions of a panel of synthetic peptides. This supports the immunologic relevance of the binding assay, and emphasizes the importance of determinant selection in defining the immune response of individuals. We have also examined the capacity of a panel of DR-restricted peptides to compete with one another for binding to DR1. The results obtained are compatible with a single peptide-binding site on DR molecules. The peptide-binding capacity of the four different DR types (DR1, DR2, DR5, and DR52a) has been further examined by testing a collection of 133 different peptides. This collection is unbiased with respect to previously known DR binding and restrictions, and includes peptides of eukaryotic, bacterial, and viral origins. It was found that: 1) approximately 15 to 35% of the peptides tested bound any given DR type; 2) DR-binding capacities appeared to correlate with each other, suggesting that different alleles of the DR isotype may recognize related structures on an Ag molecule; and 3) despite the statistical correlation between binding capacity of different DR types, approximately 50% of the peptides that were positive binders still were specific in that they could bind only one of the four DR molecules tested. Degenerate binding (i.e., binding to most or all the DR molecules tested) was detected in only a minority of the cases analyzed (approximately 25%).

Interactions of neomycin with monomolecular films of polyphosphoinositides and other lipids

The interactions of calcium and the aminoglycosidic antibiotic, neomycin, with various lipids were investigated in monomolecular films. Lipids were spread over a subphase of 0.05 M N-2- hydroxyethylpiperazine-N′-2- ethanesulfonic acid , pH 7.0, and NaCl to give an ionic strength of 0.2. Measurements of surface pressure (π) were taken with a Wilhelmy balance. In the absence of Ca 2+, 1 μM–1 mM neomycin in the subphase decreased π (i.e. condensed films) of all acidic lipids tested. In the presence of 1 mM Ca 2+, neomycin did not change π of films of phosphatidylserine, phosphatidylinositol and phosphatidic acid while it lowered π of cardiolipin and cerebroside sulfate films. A unique pattern of interaction was observed with polyphosphoinositide monolayers. In the absence of Ca 2+, 1 μM neomycin decreased π followed by an increase of π at higher neomycin concentrations. Ca 2+ (1 mM) condensed the film significantly more than did neomycin. However, as little as 1 μM neomycin induced expansion of the calcium/lipid film which at 1 mM neomycin reached the same π as in the absence of Ca 2+. Such expansion was observed at all pressures of the film including the collapse pressure indicating a strong ‘complex’ between the drug and polyphosphoinositide not antagonized by Ca 2+. In the absence of possible hydrophobic interactions, both the condensation and the expansion of the film should be mediated by ionic forces. Combined in vivo and in vitro evidence is discussed to suggest the polyphosphoinositides as the physiological receptors for aminoglycosides in the mammalian cell membrane.

Two Generations of Elderly in the Changing American Family: Implications for Family Services

Coping with the problems of growing old may be complicated by demands for economic, psychological, and social support for aging parents. Second generation children facing major age-related role shifts may not be equipped to provide such supports. Both generations are coping with their own aging process as well as with the changing family relationships caused by the process. Where such intergenerational family compositions exist, service providers must be able to understand the accompanying unique interaction patterns and maximize opportunities that can strengthen these relationships.