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PubMed1992

The evolution of neural circuits controlling feeding behavior in frogs.

Our approach to understanding motor systems is a phylogenetic, 'outside-in' approach, the goal of which is to identify behavioral transitions during phylogenesis and elucidate their neurological basis. In this paper, we review the results of recent behavioral, biomechanical and neurological studies on frog feeding behavior. These studies show that highly protrusible tongues have evolved numerous times independently among frogs, and that the biomechanics and neuromuscular control of feeding behavior have been transformed repeatedly during frog evolution. Many of the independent lineages possess unique biomechanical mechanisms for protracting their tongues and unique neural mechanisms for coordinating feeding behavior. In frogs, there has been considerable evolution at the interface between reticular central pattern generators (CPGs) associated with feeding and sensory feedback circuits that modulate feeding motor output. In particular, the roles of hypoglossal and glossopharyngeal sensory feedback appear to have been relatively plastic in their evolution. Prey-type dependence of hypoglossal sensory feedback in Rana suggests that the interaction between descending visual control and sensory feedback also may be evolutionarily plastic. Comparative studies have found that motor systems sometimes evolve conservatively across morphological and behavioral transitions (i.e., the shoulder in birds) or, alternatively, they may be subject to considerably more evolutionary change than is reflected in morphological characteristics (i.e., feeding in cichlids). We hypothesize that the CPG circuits for feeding behavior in the reticular formation may evolve conservatively because they are highly integrated, multifunctional networks which cannot be optimized for one function without compromising others. In contrast, the interfaces between the CPG, sensory feedback and descending control should be less constrained. When changes in motor patterns occur during evolution, it is likely that sensory feedback or descending control may be involved.

Animals↗

PubMed1977

Environment and the skin.

The skin is an important interface between man and his environment; it is an important portal of entry for hazardous agents and a vulnerable target tissue as well. It is a uniquely accessible model system for detecting hazards and for studying mechanisms of a wide variety of biologic funcitons. Environmental causes of skin reactions comprise a vast array of physical, chemical and biological agents. To appreciate the role of the skin as an interface with man's environment, it is necessary to understand the multiple adaptive mechanisms, and the defenses of the skin against the environmental stresses. The skin is endowed with a versatile group of defenses against penetration, fluid loss from the body, thermal stress, solar radiation, physical trauma and microbial agents. Patterns of adverse response range in quality and intensity from uncomplicated itching to metastatic neoplasia. Environmental problems comprise a large segment of disabling skin disease. Although critical epidemiologic data is limited, cutaneous illnesses comprise a significant segment of occupational disease. This represents a significant loss in productivity and a major cause of disability. The most serious research needs include the development of surveillance systems for identifying skin hazards and determining frequency of environmental skin disease; the development of new models for studying cutaneous penetration; the elucidation of the mechanisms of nonallergic inflammatory reactions (primary irritation) and of the accommodation phenomenon; the development of more sensitive models for predicting adverse responses to marginal irritants; the utilization of modern skills of immunobiology and immunochemistry to elucidate mechanisms of allergic responses; the launching of epidemiologic studies to determine the long term effects of PCBs and associated compounds such as dioxins; and the expansion of research in the mechanisms of skin cancer in relation to susceptibility, genetic and metabolic considerations, ultraviolet light, and phototoxic agents.

Dermatitis, Contact↗

PubMed1990

A novel mechanism of heme-heme interaction in the homodimeric hemoglobin from Scapharca inaequivalvis as manifested upon cleavage of the proximal Fe-N epsilon bond at low pH.

The CO-binding kinetics and the optical spectra of the NO derivative of the homodimeric hemoglobin from Scapharca inaequivalvis have been investigated over the range between pH 7.0 and 2.0. In the deoxygenated derivative, protonation of the proximal imidazole at very low pH values and the consequent cleavage of the Fe-N epsilon bond result in a approximately 50-fold enhancement of the rate constant for CO binding, as found in other hemoproteins. However, in the case of the hemoglobin from S. inaequivalvis, the pH profile displays a cooperative behavior (n = 1.8 +/- 0.1), a unique feature that differentiates this protein from any other hemoprotein investigated thus far. Cleavage of the proximal bond in the NO derivative of S. inaequivalvis hemoglobin likewise displays a very steep pH transition. The mode of assembly of the homodimer, in which the heme-carrying E and F helices provide the subunit interface and bring the hemes at a much shorter distance (18.4 A) than in vertebrate hemoglobins, is likely to provide the structural basis for this unique behavior.

Animals↗

PubMed1989

Intermediates on the reassociation pathway of phosphofructokinase I from Escherichia coli.

The folding and association pathway of the allosteric phosphofructokinase from Escherichia coli has been investigated after complete denaturation of the protein in guanidine hydrochloride by spectroscopical methods, fluorescence and circular dichroism. Three successive processes can be observed during the renaturation of this protein. First, a fast reaction, detected by fluorescence, results in the formation of a (partially) structured monomer. Second, two monomers associate into a dimeric species. This step involves the shielding of the unique tryptophan residue, Trp 311, from the aqueous solvent, and it corresponds to the formation of the interface containing the effector binding site. The presence of ATP during renaturation increases the rate of formation of this dimeric species. The other ligands of the enzyme have no effect on this reaction as well as on the whole reactivation. Finally, the enzymatic activity is regained during the third slowest step. This last reaction is due to the association of two dimers into the native tetrameric structure. The presence of fructose 6-phosphate does not increase the rate of reactivation, even though this ligand strongly stabilizes the native enzyme against denaturation by bridging the interface corresponding to the active site. The self-assembly of phosphofructokinase from E. coli from its unfolded and separated chains follows a specific order in the formation of the interactions between subunits and involves a dimeric intermediate with a defined geometry.

Allosteric Regulation↗

PubMed1991

Counselling at the cultural interface: is getting back to roots enough?

This paper attempts to view counselling in its cultural context. The central issue addressed relates to the possibly unique position which psychiatric nurses occupy in relation to this issue. It is argued that psychiatric nurses have an opportunity to challenge some of the complexities and assumptions of traditional counselling models, and contribute towards the development of a helping approach, for those who are culturally 'different', which is both authentic and flexible. After tracing the notion of cultural identity and outlining the disempowering experience of many from the cultural minority groups, when encountering the British psychiatric system, the writer considers the relevance of the Western counselling tradition in relation to those who are thus disempowered. Viewed from the complexity of human experience and cultural variability, it is claimed that many of the assumptions and premises of this tradition are themselves disempowering. An argument is made for that kind of authentic helping whose genesis is the recognition of clients in their cultural setting and which is flexible enough to respond to the individual and not merely her/his cultural grouping. With such a framework, the writer feels that psychiatric nurses could occupy a vital role, whose goal would be to re-empower individuals with diverse cultural traditions, at both a micro and macro level.

Attitude to Health↗

PubMed1986

Glial bundle formation in spinal roots following experimental neuronopathy.

Spinal motor neurons and dorsal root ganglion cells were caused to degenerate by axoplasmic transport of toxic lectins via the sciatic nerve. Within a few months, loss of axons and glial bundle formation were seen in the proximal portions of the L4-6 ventral and dorsal roots. The glial bundles observed were structurally the same as those described in humans, but they were occasionally also invested with Schwann cell cytoplasmic processes, the cell membrane of which was directly apposed to that of astrocytes. Basal lamina surrounding the outer surface of the bundles was shared by these two as a continuous sheet. This unique complex of astroglial and Schwann cell processes, completely covered by basal lamina, may be a newly formed interface between the central and peripheral nervous systems and thus may severe as a guide and potential pathway for regenerating neurites.

Animals↗

PubMed1992

The art of mammographic positioning.

The discovery of clinically occult breast cancer creates an exciting opportunity to alter the natural history of one of the major killers of women in our society. The skills required for this endeavor depend on high-quality images that provide the mammographer with sufficient information to construct three-dimensional perceptions recognizable as departures from normal architecture. Altering the natural course of breast cancer depends on early detection. Early detection of breast cancer depends on high-quality imaging techniques. Paramount among the imaging techniques for breast cancer detection is mammographic positioning. Optimal mammographic positioning is achieved by understanding the capabilities of available dedicated mammographic equipment and applying this understanding to take full advantage of natural breast mobility in overcoming various anatomic limitations. Compression of breast tissue, essential for proper parenchymal imaging, is achieved by moving one surface of the breast toward the other. The concept of moving the mobile surface of the breast toward the more fixed and immobile surface has been stressed as an important principle in optimizing the amount of tissue that can be imaged on standard mammographic views. Visualizing the fine details of a lesion or the margins of an area of clinical or perceived radiographic concern may be crucial to determining the need for biopsy. Visualization of such details is best achieved by projecting the suspected lesion into interface with adjacent radiolucent fat through separation of overlapping parenchyma by using spot compression or by tangential imaging against subcutaneous fat. Unique problems require creative, tailored solutions. Such tailoring is made less difficult by understanding and using equipment capability with breast anatomy and mobility. The very small, very large, or very dense breast can be imaged properly with modified techniques. Likewise, the augmented breast, mastectomy site, or axilla can be imaged with specialized techniques. Artistic application of these mammographic positioning principles will be rewarded with high-quality images, fewer missed breast cancers, and more lives saved.

Breast Neoplasms↗

PubMed1991

Structure of porcine insulin cocrystallized with clupeine Z.

The crystal structure of NPH-insulin, pig insulin cocrystallized with zinc, m-cresol and protamine, has been solved by molecular replacement and refined using restrained least-squares refinement methods. The final crystallographic R factor for all reflections between 2 and 10 A is 19.4%. The insulin molecules are arranged as hexamers with two tetrahedrally coordinated Zn atoms in the central channel and one m-cresol bound to each monomer near His B5. One protamine binding site has been unequivocally identified near a dimer-dimer interface, although most of the polypeptide is crystallographically disordered. The conformation of the insulin moiety and the structural differences between the three unique monomers have been analysed. The zinc and m-cresol environments are described and the nature of the protamine binding site is outlined.

Animals↗

PubMed1987

The primary structures of the major and minor hemoglobin-components of adult Andean goose (Chloephaga melanoptera, Anatidae): the mutation Leu----Ser in position 55 of the beta-chains.

The primary structures of the hemoglobin components Hb A and Hb D of the adult Andean Goose (Chloephaga melanoptera) are presented. The globin chains were separated on CM-Cellulose in 8M urea buffer. The amino-acid sequences were established by automatic Edman degradation of the globin chains and of the tryptic peptides in liquid- and gas-phase sequenators. The sequences are aligned with those of Greylag Goose (Anser anser) as a biological reference and other sequences of birds. A detailed evaluation of all residues of Andean Goose hemoglobins on the basis of the 12000 known avian globin sequences leads to a molecular pattern for high-altitude respiration of geese. The replacement of functional and structural importance is the unique occurrence of the residue beta 55 Leu----Ser (all other exchanges are functionally neutral), interrupting the same alpha 1 beta 1-interface contact (alpha 119-beta 55) that accounts for high-altitude respiration of the Barheaded Goose (Anser indicus); there the mutation is found on alpha A 119. Loosening the constraints of this interface must be interpreted as a destabilization of the low-affinity T-structure in favour of the high-affinity R-structure. The structural and functional significance of this interface for the molecular biology of high-altitude respiration of the Andean Goose and Barheaded Goose is discussed. Since Hb A consists of alpha A2 beta 2 and Hb D consists of alpha D2 beta 2 the mutation occurring in blood of the Andean Goose affects both hemoglobins whereas in the case of the Barheaded Goose only Hb A is affected. These results show that Hb D can be considered a biological reserve to enlarge situatively the normal hemoglobin function. A general molecular pattern for permanent (selective advantage of high intrinsic oxygen affinity) and transitory (selective advantage of graded oxygen affinities) adaptation to hypoxia is discussed. A survey on the sequence homology of the globin chains of geese (Anserinae) and ducks (Anatinae) is given.

Altitude↗

PubMed1989

The use of soot analysis as an investigative tool in aircraft fires.

Traditionally, carboxyhemoglobin analysis has been used to determine the extent of respiration during a postcrash fire. This is a useful and informative measurement, but advances in the chemical analysis of soot samples provide a new and useful forensic tool for the investigation of deaths by fire. One of the latest analytical techniques is a computer-interfaced pyrolysis mass spectrometry. Soot consists of a high percentage of carbon as well as fragments of the original polymer that are unique to that particular material. Consequently, analysis and identification of the fragment pattern makes it possible to identify the original material from which the soot was generated. In pyrolysis mass spectrometry the soot is pyrolyzed into the ion source and the resulting ion pattern is computer analyzed to identify the polymeric system or systems that generated the soot. Analysis of soot samples collected from the upper respiratory tract of aircraft accident victims and from the accident scene can provide information on the type of toxic insult (identifies specific toxic products), the material(s) that burned and generated the toxic atmosphere, and the relative time of survival following the crash. This technique has been applied to the investigation of fire deaths in a hotel fire and will be used to illustrate the identification of the materials that burned, the toxic products, and the potential for aircraft accident investigations.

Accidents, Aviation↗

PubMed1992

Comparison between B-scan ultrasound and MRI in the detection of diabetic vitreous hemorrhage.

The efficacy of proton magnetic resonance imaging (MRI) was evaluated and compared with that of B-scan ultrasound in the detection and differentiation of diabetic vitreous hemorrhage. Although conventional spin-echo MRI could not locate vitreous hemorrhages, gradient-recalled-echo (GRE) MRI readily did so. The aberrant signals appeared to originate from the interfacing between hemorrhages and the vitreous, and possibly also from the paramagnetic effect of the ferrous ion. The information provided by boundary/susceptibility detection, unique to the GRE sequence, is useful in delineating the extent of vitreous hemorrhage and hemolysis. However, for the diagnosis and follow up of diabetic vitreous hemorrhages, MRI appears no more informative than B-scan ultrasonography.

Aged↗

PubMed1992

Antecedents and outcomes of work-family conflict: testing a model of the work-family interface.

A comprehensive model of the work-family interface was developed and tested. The proposed model extended prior research by explicitly distinguishing between work interfering with family and family interfering with work. This distinction allowed testing of hypotheses concerning the unique antecedents and outcomes of both forms of work-family conflict and a reciprocal relationship between them. The influence of gender, race, and job type on the generalizability of the model was also examined. Data were obtained through household interviews with a random sample of 631 individuals. The model was tested with structural equation modeling techniques. Results were strongly supportive. In addition, although the model was invariant across gender and race, there were differences across blue- and white-collar workers. Implications for future research on the work-family interface are discussed.

Adaptation, Psychological↗

PubMed2026

Structural insights into histone mimicry by the small hepatitis delta antigen.

Hepatitis delta virus (HDV) is a satellite RNA virus that requires hepatitis B virus (HBV) for propagation but replicates its genome independently in the nucleus. The small form of the hepatitis delta antigen (S-HDAg) is essential for replication and is regulated by post-translational modifications. Acetylation at lysine 72 (K72ac) enables S-HDAg to interact with the bromodomain (BRD) of the host chromatin remodeler bromodomain adjacent to zinc finger domain protein 2B (BAZ2B) to promote viral replication. However, the structural basis for this interaction has remained elusive. Here, we provide structural and biophysical insights into this interaction through quantitative binding assays and X-ray crystallography. Isothermal titration calorimetry revealed that BRDs of BAZ2B and its close homolog BAZ2A bind to the viral peptide weakly, with BAZ2A-BRD exhibiting a modestly higher affinity. The crystal structure of BAZ2A-BRD in complex with the S-HDAg-K72ac peptide demonstrates an inverted binding orientation relative to canonical histone ligands, rationalizing the weak interaction. Mutagenesis studies confirmed the critical binding interface both in vitro and in cells. These findings elucidate the molecular mechanism by which HDV co-opts host BAZ2 bromodomains via a unique, weak-affinity interaction, providing a structural framework for understanding viral replication.

Hepatitis delta Antigens↗

PubMedDate not supplied

Lipoprotein(a) impairs generation of plasmin by fibrin-bound tissue-type plasminogen activator. In vitro studies in a plasma milieu.

Apoprotein(a), (apo[a]), the specific antigen of lipoprotein(a) (Lp[a]), consists of structural domains (a serine protease unit, kringles 4 and 5) with marked homology to those of the corresponding domains in plasminogen. In this study, we have investigated the impact of this unique structural mimicry on the binding and activation of plasminogen by fibrin-bound tissue-type plasminogen activator at the plasma-fibrin interface. We found that the total amount of plasmin generated on the surface of fibrin was decreased in the presence of high concentrations of Lp(a): 197 +/- 65 fmol in plasmas with greater than 60 mg/dl Lp(a) versus 287 +/- 112 fmol in control plasmas. A similar effect was also apparent in the corresponding euglobulin fractions (554 +/- 169 fmol versus 754 +/- 310 fmol), the latter lacking the plasminogen-binding proteins alpha 2-antiplasmin and histidine-rich glycoprotein, but containing Lp(a). The difference between plasma samples was significant (p less than 0.05) as calculated from the percent decrease in plasmin generated from plasmas with high levels of Lp(a) relative to that generated in the paired controls with low Lp(a) levels. The involvement of Lp(a) was verified in a reconstituted system consisting of normal human plasma supplemented with 100 mg/dl of either purified Lp(a) or low density lipoprotein. Lp(a) produced a decrease of 30% in the generation of plasmin (180 fmol versus 255 fmol in plasma, and 485 fmol versus 705 fmol in the euglobulin fraction). Moreover, using a radiolabeled sheep antibody against human apo(a), we were able to demonstrate the binding of 40 fmol Lp(a) to fibrin during ongoing plasminogen activation. These results indicate that Lp(a) impairs the binding of plasminogen to fibrin and thereby decreases the generation of plasmin by occupying C-terminal lysine residues unveiled on the fibrin surface by plasmin degradation as recently reported (Circulation 1990;82[suppl III]:III-92). In consequence, impairment of fibrinolysis and accumulation of Lp(a) at sites of vascular injury may occur, factors that may be important in the development of atherosclerosis and associated thrombosis.

Blood↗

PubMed1990

The physiology of the blood-brain barrier.

The BBB is a dynamic interface between blood and the central nervous system enabling the brain to keep an optimal internal environment. The endothelial cells of the brain capillaries are unique epithelial-like cells that are fused together by tight junctions and have a low pinocytotic activity. The entry of a specific substance will, therefore, mainly depend on its lipid solubility, and whether or not it has access to any of the carriers in the endothelial cells. Enzymatic degradation in the endothelium can prevent entry into the brain of substances that do enter the endothelial cells. Astrocytes may have an important role by inducing and upholding some barrier functions. An intact BBB is evidently important for optimal brain function. Manipulation of the BBB to allow entry of therapeutic agents may be justified under certain circumstances but should be done with caution until we know more about the long-term consequences of such manipulation.

Animals↗

PubMed1986

The health of the chronically mentally ill: a review of the literature.

This paper reviews three areas of research on the health of the chronically mentally ill: epidemiological studies on this population, studies exploring the clinical interface of physical and psychiatric disorder, and studies illuminating barriers to adequate health care for this population. Its purpose is to increase our understanding of the unique health problems facing the chronically mentally ill so that appropriate interventions can be developed. The review suggests that greater attention to this area should result in improved physical health as well as improved psychiatric intervention. The implications for policy, practice, and research are discussed.

Chronic Disease↗

PubMed2026

EPIC: multi-objective guided diffusion for epitope design in TCR-pMHC complexes.

MOTIVATION: T cell receptor (TCR) recognition of peptide-major histocompatibility complex (pMHC) complexes is central to adaptive immunity, yet rational design of immunogenic epitopes remains elusive due to complex triplet binding constraints and data scarcity. No existing method can generate epitopes satisfying simultaneous requirements for antigenicity, MHC presentation, and TCR specificity. RESULTS: We present EPIC, a multi-objective diffusion framework that decomposes TCR-pMHC binding into three biologically grounded sub-tasks, enabling training-free gradient guidance without end-to-end retraining. By integrating ESM-based classifiers with a peptide diffusion generator, EPIC leverages heterogeneous immunological interaction datasets to generate diverse, context-aware epitopes. EPIC-designed top-three epitopes achieve lower predicted interface energies compared to ground-truth epitopes in 78.31% of test cases, while maintaining 80.1% sequence novelty and comparable structural confidence. Generated epitopes exhibit 100% uniqueness, high diversity (64.05%), and high antigenicity scores (0.4723). To our knowledge, EPIC is the first computational framework capable of de novo epitope design while explicitly integrating the triplet constraints of TCR-pMHC binding. This paradigm shift from discovery to design unlocks new potential for personalized cancer vaccines, precision adoptive T cell therapy, and rapid response to emerging infectious diseases. AVAILABILITY AND IMPLEMENTATION: The source code of EPIC is available at https://github.com/Octopus125/EPIC and archived on Zenodo (DOI: 10.5281/zenodo.18537646).

Receptors, Antigen, T-Cell↗

PubMed1988

Photochemical reactions of dyes and olefins in monolayer films and supported multilayers.

The studies cited in this paper demonstrate that the unique environment provided by L. B. films and supported multilayers can produce a variety of molecular effects on photochemical reactivity that can, in turn, result in films, interfaces or surfaces having macroscopic properties which can be modulated by light. Although these investigations have been focused on molecular reactivity in films and how it can be modified (or persist unchanged), the results suggest several possible technological applications which might result from investigations directed more closely to them.

Alkenes↗