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At least 217 records · Page 12Linked to original sources

PubMed2002

Dynamic kinetic resolution via dual-function catalysis of modified cinchona alkaloids: asymmetric synthesis of alpha-hydroxy carboxylic acids.

A highly enantioselective catalytic transformation of racemic alpha-hydroxy acids to optically active alpha-hydroxy acids is reported. A new procedure was developed for the condensation of racemic alpha-hydroxy acids with trichloromethyl chloroformate (diphosgene) at room temperature in the presence of activated charcoal to form 5-substituted-1,3-dioxolane-2,4-diones in 90-100% yield. An efficient dynamic kinetic resolution of 5-aryl dioxolanediones was realized via a modified cinchona alkaloid-catalyzed alcoholytic opening of the dioxolanedione ring, generating a variety of optically active alpha-hydroxy esters in 91-96% ee and 61-85% chemical yield. In this dynamic kinetic resolution, the modified cinchona alkaloid was found to serve dual catalytic roles, mediating both the rapid racemization of the 5-aryl dioxolanediones and the enantioselective alcoholytic ring opening of the 5-aryl dioxolanediones. Consequently, both enantiomers of the 5-aryl dioxolanediones were converted to highly enantiomerically enriched aromatic alpha-hydroxy esters in yields (61-85%), far exceeding the maximum of 50% for a normal kinetic resolution. This development not only represents an expansion of the scope of asymmetric acyl-transfer catalysis of synthetic catalysts but also provides a new approach for the development of efficient chemical dynamic kinetic resolutions promoted by a single catalyst. 5-Alkyl dioxolanediones were resolved by a conventional but highly enantioselective kinetic resolution to provide alpha-hydroxy acids and esters in high optical purity and good yields.

Carboxylic Acids↗

PubMed2006

Key role of the Lewis base position in asymmetric bifunctional catalysis: design and evaluation of a new ligand for chiral polymetallic catalysts.

New chiral ligands for asymmetric polymetallic catalysts were designed on the basis of the assumption that the higher-order assembly structure is stabilized by modifying the modular unit. The designed ligands 6 and 7 contained a scaffolding cyclohexane ring with a Lewis base phosphine oxide directly attached to the scaffold. A module in the polymetallic complex contains two metals per ligand, and a stable 6-, 5-, 5-membered fused chelation ring system should be generated. Synthesis of these ligands is simple and high yielding, using a catalytic dynamic kinetic resolution promoted by the Trost catalyst as a key step. Ligand function was assessed in a catalytic asymmetric ring-opening reaction of meso-aziridines with TMSCN, a useful reaction for the synthesis of optically active beta-amino acids. The Gd complex generated from Gd(OiPr)3 and the ligand was a highly active and enantioselective catalyst in this reaction. Enantioselectivity was reversed compared to the previously reported d-glucose-derived catalyst containing the same chirality of the individual module. ESI-MS analysis and X-ray crystallographic studies indicate that the assembly state of the modules in the polymetallic catalysts differs depending on the chiral ligand. The difference in the higher-order structure stems from a subtle change (one carbon) in the position of the Lewis base relative to the Gd metal. The change in the higher-order structure of the polymetallic complex led to a dramatic reversal of the enantioselectivity and increased catalyst activity.

Aziridines↗

PubMed2000

Triggering of earthquake aftershocks by dynamic stresses.

It is thought that small 'static' stress changes due to permanent fault displacement can alter the likelihood of, or trigger, earthquakes on nearby faults. Many studies of triggering in the near-field, particularly of aftershocks, rely on these static changes as the triggering agent and consider them only in terms of equivalent changes in the applied load on the fault. Here we report a comparison of the aftershock pattern of the moment magnitude Mw = 7.3 Landers earthquake, not only with static stress changes but also with transient, oscillatory stress changes transmitted as seismic waves (that is, 'dynamic' stresses). Dynamic stresses do not permanently change the applied load and thus can trigger earthquakes only by altering the mechanical state or properties of the fault zone. These dynamically weakened faults may fail after the seismic waves have passed by, and might even cause earthquakes that would not otherwise have occurred. We find similar asymmetries in the aftershock and dynamic stress patterns, the latter being due to rupture propagation, whereas the static stress changes lack this asymmetry. Previous studies have shown that dynamic stresses can promote failure at remote distances, but here we show that they can also do so nearby.

Journal Article↗

PubMed2026

NextLongIso: a comprehensive Nextflow pipeline for multi-dimensional long-read RNA-seq analysis.

SUMMARY: Long-read RNA sequencing technologies, including Pacific Biosciences (PacBio) and Oxford Nanopore Technologies (ONT), enable direct characterization of full-length transcripts and transcriptome complexity. However, analysis of long-read RNA-seq data remains fragmented across multiple tools, limiting the ability to obtain a unified view of transcript structure, expression, and regulatory variation in long-read transcriptomes. We present NextLongIso, a scalable and reproducible Nextflow pipeline that enables coordinated analysis of multiple layers of transcript regulation. Rather than focusing solely on transcript reconstruction, NextLongIso integrates transcript discovery with downstream regulatory analyses to jointly characterize alternative splicing, isoform switching, transcript boundary dynamics (including alternative promoters and polyadenylation), and transposable element-associated transcription from both PacBio and ONT datasets. By eliminating complex cross-tool data harmonization, this unified framework facilitates the transition from transcript identification to functional interpretation of transcriptomic variation. AVAILABILITY AND IMPLEMENTATION: NextLongIso is implemented in Nextflow and is freely available at github: https://github.com/YidanSunResearchLab/nf-LongIso.git and Zenodo: https://doi.org/10.5281/zenodo.21049837.

Software↗

PubMed2004

A global view of the selection forces in the evolution of yeast cis-regulation.

The interaction between transcription factors and their DNA binding sites is key to understanding gene regulation. By performing a genome-wide study of the evolutionary dynamics in yeast promoters, we provide a first global view of the network of selection forces in the evolution of transcription factor binding sites. This analysis gives rise to new models for binding site activity, identifies families of related binding sites, and characterizes the functional similarities among them. We discovered rich and highly optimized selective pressures operating inside and around these families. In several cases, this organization reveals that a single transcription factor has multiple functional modes. We demonstrate how such functional heterogeneity is related to the binding site's affinity and how it is exploited in transcription programs.

Binding Sites↗

PubMed2001

NMR imaging of falling water drops.

The falling water drop is a simple model for studying phenomena related to chemical extraction, where two immiscible phases are dynamically blended to promote the transport of solute molecules from one phase to the other. Convective motion inside the drop significantly influences the extraction efficiency. Whereas optical and tracer methods are model bound or invasive, NMR imaging is noninvasive, direct, and applicable to nontransparent media. The first NMR measurements of a water drop falling through air are reported. It is shown that, in drops from pure water, large-scale convection rolls are observed in contrast to drops with the surface tension lowered by surfactants.

Journal Article↗

PubMed2002

Regulation of the pollen-specific actin-depolymerizing factor LlADF1.

Pollen tube growth is dependent on a dynamic actin cytoskeleton, suggesting that actin-regulating proteins are involved. We have examined the regulation of the lily pollen-specific actin-depolymerizing factor (ADF) LlADF1. Its actin binding and depolymerizing activity is pH sensitive, inhibited by certain phosphoinositides, but not controlled by phosphorylation. Compared with its F-actin binding properties, its low activity in depolymerization assays has been used to explain why pollen ADF decorates F-actin in pollen grains. This low activity is incompatible with a role in increasing actin dynamics necessary to promote pollen tube growth. We have identified a plant homolog of actin-interacting protein, AIP1, which enhances the depolymerization of F-actin in the presence of LlADF1 by approximately 60%. Both pollen ADF and pollen AIP1 bind F-actin in pollen grains but are mainly cytoplasmic in pollen tubes. Our results suggest that together these proteins remodel actin filaments as pollen grains enter and exit dormancy.

Actin Depolymerizing Factors↗

PubMed2005

The role of protein and surfactant interactions in membrane-protein crystallization.

The interactions leading to crystallization of the integral membrane protein bacteriorhodopsin solubilized in n-octyl-beta-D-glucoside were investigated. Osmotic second virial coefficients were measured by self-interaction chromatography in the presence of sodium malonate, sodium formate and ammonium sulfate. Attractive protein-detergent complex (PDC) interactions were observed as the surfactant cloud-point temperature was approached for each salt, suggesting that surfactant interactions may play an important role in promoting PDC crystallization. Dynamic light scattering and tensiometry measurements show that the interaction trends are strongly influenced by micelle structure and surfactant phase behavior, both of which are sensitive to salt and surfactant concentration. Overall, detailed investigations using a combination of experimental techniques can provide insight into the complex nature of PDC interactions, which is essential to developing rational approaches to membrane-protein crystallization.

Bacteriorhodopsins↗

PubMed1992

An interpersonal-epistemological curriculum model for nurse education.

This paper proposes a curriculum model for nurse education which holds forms of knowledge and interpersonal relationships as key issues if nurse education is to develop autonomous, reflective, critical practitioners. By adopting areas of cognitive interest, principles of andragogy and the concept of reflection-in-action, the model provides a heuristic tool which attempts to enable the provision of a nurse education which is devoted to adult learning processes and relevant to the development of education in the practice setting. The technical, practical and emancipatory areas of cognitive interest provide an understanding of learning domains which require different knowledge bases, methods of learning and forms of assessment to each other. The pedagogy/andragogy dichotomy is presented to reflect two teaching paradigms. The former approach is derived from the activity of teaching children and provides for passive dependence. The latter is more appropriate to adult learning and student self-direction. The model attempts to promote the transitional dynamic which moves the student nurse toward a state of greater self-direction. Finally, the concept of reflection-in-action is discussed in an attempt to ensure that the areas of cognitive interest and the learning strategies are inextricably linked to the practice component of a professional nurse education. All three dimensions are combined to show how each should develop in unison as the professional education of the nurse proceeds along a chronological dimension.

Clinical Competence↗

PubMed1983

Role of dimethyl sulfoxide in prostaglandin-thromboxane and platelet systems after cerebral ischemia.

Direct and empirical evidence indicates that intravenous administration of DMSO can arrest or reverse cerebral and extracerebral ischemia following experimental or clinical injury. When the delivery of oxygen and nutrients to the tissue is deficient or unavailable (as in ischemia), cell damage or death with all its attending pathological consequences becomes an end-point. In the brain, this equates to build-up of intracranial pressure, impairment of neural transmission to vital centers, and loss of function or death. We have reviewed a number of studies that show the usefulness of DMSO in preventing significant pathology from developing in various experimental injury models and in clinical subjects. We have proposed that the action of DMSO in biochemical, morphological, and functional subsystems is not specific but rather interactive. Figure 5 illustrates this point. Any one effect by DMSO on these subsystems that does not affect the others seems highly unlikely. How DMSO or similar drugs affect these systems, could provide important clues in clarifying the pathogenesis of ischemia and in reducing its severity. We conclude from the available evidence that ischemic injury is a dynamic process constantly promoting biochemical, vascular, and morphological changes and that DMSO is able to intervene at various levels of this pathochemical cascade. DMSO may do this by its ability to normalize tissue perfusion when this is lacking or impaired. We speculate that this effect by DMSO is predominantly on the PG-TX and platelet systems, since these appear to be the most important candidates implicated in vessel occlusion and spasm. It is further concluded from the available and theoretical evidence presented here, that clinical trials using DMSO in cerebral and extracerebral organ ischemia should be designed in order to evaluate the efficacy of this compound to other antithrombogenic therapies. It is reasonable to assume that DMSO may provide a primary approach to the treatment of cerebral, myocardial, renal, and platelet-induced ischemic disorders.

Animals↗

PubMed2006

Signal recognition particle-dependent inner membrane targeting of the PulG Pseudopilin component of a type II secretion system.

The pseudopilin PulG is an essential component of the pullulanase-specific type II secretion system from Klebsiella oxytoca. PulG is the major subunit of a short, thin-filament pseudopilus, which presumably elongates and retracts in the periplasm, acting as a dynamic piston to promote pullulanase secretion. It has a signal sequence-like N-terminal segment that, according to studies with green and red fluorescent protein chimeras, anchors unassembled PulG in the inner membrane. We analyzed the early steps of PulG inner membrane targeting and insertion in Escherichia coli derivatives defective in different protein targeting and export factors. The beta-galactosidase activity in strains producing a PulG-LacZ hybrid protein increased substantially when the dsbA, dsbB, or all sec genes tested except secB were compromised by mutations. To facilitate analysis of native PulG membrane insertion, a leader peptidase cleavage site was engineered downstream from the N-terminal transmembrane segment (PrePulG*). Unprocessed PrePulG* was detected in strains carrying mutations in secA, secY, secE, and secD genes, including some novel alleles of secY and secD. Furthermore, depletion of the Ffh component of the signal recognition particle (SRP) completely abolished PrePulG* processing, without affecting the Sec-dependent export of periplasmic MalE and RbsB proteins. Thus, PulG is cotranslationally targeted to the inner membrane Sec translocase by SRP.

Amino Acid Sequence↗

PubMed2006

A large-scale neurocomputational model of task-oriented behavior selection and working memory in prefrontal cortex.

The prefrontal cortex (PFC) is crucially involved in the executive component of working memory, representation of task state, and behavior selection. This article presents a large-scale computational model of the PFC and associated brain regions designed to investigate the mechanisms by which working memory and task state interact to select adaptive behaviors from a behavioral repertoire. The model consists of multiple brain regions containing neuronal populations with realistic physiological and anatomical properties, including extrastriate visual cortical regions, the inferotemporal cortex, the PFC, the striatum, and midbrain dopamine (DA) neurons. The onset of a delayed match-to-sample or delayed nonmatch-to-sample task triggers tonic DA release in the PFC causing a switch into a persistent, stimulus-insensitive dynamic state that promotes the maintenance of stimulus representations within prefrontal networks. Other modeled prefrontal and striatal units select cognitive acceptance or rejection behaviors according to which task is active and whether prefrontal working memory representations match the current stimulus. Working memory task performance and memory fields of prefrontal delay units are degraded by extreme elevation or depletion of tonic DA levels. Analyses of cellular and synaptic activity suggest that hyponormal DA levels result in increased prefrontal activation, whereas hypernormal DA levels lead to decreased activation. Our simulation results suggest a range of predictions for behavioral, single-cell, and neuroimaging response data under the proposed task set and under manipulations of DA concentration.

Action Potentials↗

PubMed1983

Brief psychotherapy in late adolescence: a psychodynamic and developmental approach.

Four cases were discussed in which college students presented themselves in crisis for psychiatric treatment; each was dealing with a normal developmental crisis of late adolescence centering around separation-individuation issues. A type of brief psychotherapy was described which maintained the focus on the primary dynamic conflict and promoted ego development by interpreting the unconscious intrapsychic conflict. The incestuous, aggressive, and regressive themes were explored, and defenses were actively interpreted whenever they interfered with the awareness of autonomous strivings consistent with the ego ideal. Although other authors have emphasized the necessity of establishing a contract early which specifies the number of visits, we have emphasized the importance of maintaining strict therapeutic neutrality, especially regarding the duration of treatment with late adolescents. We view this as an important cornerstone of technique in assisting the healthy late adolescent in his quest for increasing autonomy, ego-ideal integration and ego mastery.

Adjustment Disorders↗

PubMed2002

Transgenic mice overexpressing insulin-like growth factor binding protein-5 display transiently decreased osteoblastic function and osteopenia.

Skeletal cells synthesize IGFs and their six IGF binding proteins (IGFBP). IGFBP-5 was reported to stimulate bone cell growth in vitro and selected parameters of osteoblastic function in vivo, but its actual effects on bone formation are not established. We investigated the direct effects of IGFBP-5 on bone remodeling in two lines of transgenic mice overexpressing IGFBP-5 under the control of the osteocalcin promoter. Static and dynamic histomorphometry revealed that IGFBP-5 transgenic mice had a transient decrease in trabecular bone volume secondary to reduced trabecular number and thickness and a transient decrease in bone mineral apposition rate. Osteoblast number was normal, indicating impaired osteoblastic function. Osteoclast number and bone resorption were normal. Total, vertebral, and femoral bone mineral densities were reduced in IGFBP-5 transgenics by 14-27% at 4 wk of age, but not in older animals. Stromal cells expressing the IGFBP-5 transgene displayed decreased expression of alkaline phosphatase, osteocalcin, core binding factor 1, and type I collagen transcripts when compared with cells from wild-type animals. In conclusion, transgenic mice overexpressing IGFBP-5 in the bone microenvironment have a transient decrease in trabecular bone volume, impaired osteoblastic function, and osteopenia.

Alkaline Phosphatase↗

PubMed2005

Meeting report: Structural determination of environmentally responsive proteins.

The three-dimensional structure of gene products continues to be a missing lynchpin between linear genome sequences and our understanding of the normal and abnormal function of proteins and pathways. Enhanced activity in this area is likely to lead to better understanding of how discrete changes in molecular patterns and conformation underlie functional changes in protein complexes and, with it, sensitivity of an individual to an exposure. The National Institute of Environmental Health Sciences convened a workshop of experts in structural determination and environmental health to solicit advice for future research in structural resolution relative to environmentally responsive proteins and pathways. The highest priorities recommended by the workshop were to support studies of structure, analysis, control, and design of conformational and functional states at molecular resolution for environmentally responsive molecules and complexes; promote understanding of dynamics, kinetics, and ligand responses; investigate the mechanisms and steps in posttranslational modifications, protein partnering, impact of genetic polymorphisms on structure/function, and ligand interactions; and encourage integrated experimental and computational approaches. The workshop participants also saw value in improving the throughput and purity of protein samples and macromolecular assemblies; developing optimal processes for design, production, and assembly of macromolecular complexes; encouraging studies on protein-protein and macromolecular interactions; and examining assemblies of individual proteins and their functions in pathways of interest for environmental health.

Environmental Health↗

PubMed2002

The need for pedagogical qualifications for teaching cardiology to undergraduate students.

OBJECTIVE: To report a training program in cardiology emphasizing changes in its pedagogical practice. These changes were put into practice by some teachers at the Medical School of Porto Alegre of the University of Rio Grande do Sul (FAMED/UFRGS) aiming to make faculty and student activities more dynamic and to promote more efficacious learning. The training program is directed at 5th semester medical students and aims at a behavioral change in teachers and students to promote more interaction, to favor exchanges, and to make the teaching-learning process easier, always maintaining the patient in the center of the medical activity. METHODS: The program emphasizes the definition of general and specific objectives for each activity to be developed by the students, with training in the area of admission to the cardiology service, with special emphasis on behavioral change in the cognitive, motor, affective, and attitudinal areas. Knowledge was developed by means of interactive seminars with initial and final assessment tests to identify students' and teachers' performance. The students were evaluated in an immediate, continuous, and progressive way in their daily activities and through comparison of the results of 2 tests, one applied at the beginning of the training and the other at its end. These 2 tests contained the same questions. RESULTS: We systematically assessed 560 students over 4 years. The mean grades of the tests performed prior to and after the 244 seminars were 7.38+/-1.66 and 9.17+/- 0.82, respectively (p<0.0001). For the tests applied at the beginning and at the end of the training, the mean grades were 5.61+/-1.61 and 9.37+/-0.90, respectively (p<0.0001). CONCLUSION: The program proved to be efficient both for the students' learning and for assessing their performance in a systematic and objective way.

Cardiology↗

PubMed1997

Healing of 56 segmental femoral shaft fractures after locked nailing. Poor results of dynamization.

We treated 56 consecutive acute segmental femoral shaft fractures with closed static locked nailing. 12 nails were dynamized after 6 (5-10) months due to slow fracture healing and 5 united after another 5 (3-8) months. The other 7 required cancellous bone grafting and all healed uneventfully 6 (5-8) months after grafting. Since dynamization did not promote healing in most of our cases we suggest early cancellous bone grafting in cases of delayed union.

Adult↗

PubMed2000

Treadmill exercise-induced release of endothelin-1 in patients with peripheral arterial occlusive disease at Fontaine stage IIb.

BACKGROUND: Endothelin-1 (ET-1) is an endothelial vasoconstrictor mitogenic peptide which is thought to be a marker of endothelial damage and a potential participant in the pathophysiological processes of the development of atherosclerotic lesions and disease states associated with vasoconstriction and vasospasm. METHODS: To investigate the endothelin-1 release in response to dynamic exercise in patients with peripheral arterial occlusive disease (PAOD), plasma concentrations were determined by radioimmunoassay in 16 patients (14 men, 2 women, mean age 56.2 +/- 8.1 years) with peripheral arterial occlusive disease at Fontaine stage IIb and in 10 control subjects (8 men, 2 women, mean age 58.1 +/- 7.2 years) in normal health during treadmill testing (slope 5%, speed 3 km/hr). Blood samples were collected at rest from an antecubital vein, at the onset of claudication pain, and 10 minutes after exercise. RESULTS: Mean plasma endothelin-concentrations during the stress test increased significantly in the patients with arterial disease, rising from basal values of 4.4 +/- 0.6 pmol/L to values of 8.9 +/- 0.7 pmol/L at the end of the test (p < 0.0001), whereas it did not change significantly in control subjects (rising from 2.6 +/- 0.4 pmol/L to 2.7 +/- 0.5 pmol/L). Further, plasma endothelin- in the patients with arterial disease was at all times higher than in the control subjects (p < 0.0001). CONCLUSIONS: In conclusion, this study shows that in patients with peripheral arterial occlusive disease, plasma endothelin-1 increases after treadmill exercise performed until claudication pain supervenes. Raised endothelin-1 could be a marker of ischaemic acute endothelial damage and/or could contribute to increase the vascular resistance in ischaemic limbs of these patients during dynamic exercise by promoting arterial/arteriolar vasoconstriction or vasospasm.

Arterial Occlusive Diseases↗