Deconvolving molecular signatures of interactions between microbial colonies.

MOTIVATION: The interactions between microbial colonies through chemical signaling are not well understood. A microbial colony can use different molecules to inhibit or accelerate the growth of other colonies. A better understanding of the molecules involved in these interactions could lead to advancements in health and medicine. Imaging mass spectrometry (IMS) applied to co-cultured microbial communities aims to capture the spatial characteristics of the colonies' molecular fingerprints. These data are high-dimensional and require computational analysis methods to interpret. RESULTS: Here, we present a dictionary learning method that deconvolves spectra of different molecules from IMS data. We call this method MOLecular Dictionary Learning ( MOLDL: ). Unlike standard dictionary learning methods which assume Gaussian-distributed data, our method uses the Poisson distribution to capture the count nature of the mass spectrometry data. Also, our method incorporates universally applicable information on common ion types of molecules in MALDI mass spectrometry. This greatly reduces model parameterization and increases deconvolution accuracy by eliminating spurious solutions. Moreover, our method leverages the spatial nature of IMS data by assuming that nearby locations share similar abundances, thus avoiding overfitting to noise. Tests on simulated datasets show that this method has good performance in recovering molecule dictionaries. We also tested our method on real data measured on a microbial community composed of two species. We confirmed through follow-up validation experiments that our method recovered true and complete signatures of molecules. These results indicate that our method can discover molecules in IMS data reliably, and hence can help advance the study of interaction of microbial colonies. AVAILABILITY AND IMPLEMENTATION: The code used in this paper is available at: https://github.com/frizfealer/IMS_project.

Regulation of parasympathetic neurons by mast cells and histamine in the guinea pig heart.

The potential interaction between the immune system and the autonomic nervous system was examined in the cardiac ganglia of guinea pigs. Intracellular voltage recordings were used to determine the effects of mast cell degranulation on the membrane properties of parasympathetic neurons in animals actively sensitized to ovalbumin. Stimulation of mast cell degranulation by perfusion with ovalbumin (10 micrograms/ml) produced a depolarization and increase in the excitability of intracardiac neurons. These effects could be mimicked by histamine application, either by perfusion (10 microM) or by local pressure application (100 microM, 1-2 s application). In either case, histamine application resulted in a similar membrane depolarization and increase in excitability. Immunohistochemical experiments demonstrated that histamine-immunoreactive mast cells are located in close proximity to parasympathetic postganglionic neurons. The histamine response was not due to release of other neurotransmitters from adjacent nerve terminals and both the depolarization and increase in excitability were inhibited by the H1 antagonist, pyrilamine (300 nM), and were unaffected by the H2 antagonist cimetidine (5 microM). Incubation of cardiac ganglion preparations from sensitized animals with pyrilamine prior to ovalbumin perfusion resulted in the inhibition of both the depolarization and increase in excitability. These results demonstrate that mast cell degranulation, and the subsequent release of histamine, results in the stimulation of intracardiac neurons via the activation of H1 receptors. Thus, local inflammatory reactions in the cardiac tissue can lead to the rapid activation of parasympathetic neurons, thereby altering cardiac function.

Adhesion-guided in vitro morphogenesis in pure and mixed cell cultures.

The ability to understand and control the morphogenesis of mammalian cells is a fundamental objective of cell and developmental biology and tissue engineering research. Numerous processes, both biochemical and biophysical in nature, have been studied in an attempt to elucidate the mechanisms underlying this behavior. We focus here on the contributions of biophysical phenomena to the morphogenetic behavior of pure and mixed cell populations on solid surfaces in vitro. These principles are illustrated using characteristic liver tissue cells as a model system. The studies discussed demonstrate that cell-substratum and cell-cell adhesive forces are critical determinants of the ultimate morphology, cytoarchitecture, and organization achieved by these cells in vitro.

Cell-substratum adhesion strength as a determinant of hepatocyte aggregate morphology.

Cultured hepatocytes typically form multicellular aggregates which are either monolayered or spheroidal in morphology. We propose that the aggregate morphology resulting from a particular cell-substratum interaction has a biophysical basis: when cell contractile forces are greater than cell-substratum adhesion forces, spheroidal aggregates form; when cell contractile forces are weaker than cell-substratum adhesion forces, cells remain essentially spread and form monolayered aggregates. We tested this hypothesis by systematically varying the morphology of hepatocellular aggregates formed on substrata coated with a series of different concentrations of Matrigel, and correlating aggregate morphology with the cell-substratum adhesion strength measured in a shear flow detachment assay. Aggregate morphology was binary-spheroidal aggregates formed at low Matrigel concentrations and monolayered aggregates formed at high Matrigel concentrations. Cell-substratum adhesion strength was similarly binary, with low adhesion strengths correlated with spheroidal aggregates and high adhesion strengths correlated with formation of monolayered aggregates. (c) 1997 John Wiley & Sons, Inc. Biotechnol Bioeng 53: 415-426, 1997.

In vitro organogenesis of liver tissue.

The high metabolic rate of hepatocytes severely limits the mass of cells which can be transplanted without a vascular supply. We are developing an alternative approach in which vascularized tissue is grown ex vivo for anastamosis into the portal vein. Here, we discuss the key design issues for in vitro organogenesis of vascularized hepatic tissue, describe a fabrication approach for making complex degradable polymer scaffolds to organize cells in three dimensions on the scale of hundreds of microns, and demonstrate the feasibility of using these scaffolds for in vitro tissue organization in mixed-cell cultures.

Motility behavior of hepatocytes on extracellular matrix substrata during aggregation.

Aggregation of hepatocytes in culture is an important phenomenon to control in tissue engineering applications. Aggregation generally enhances maintenance of differentiated functions but inhibits cell growth. At present there exists insufficient information for rational design of substrata that control aggregation. Indeed, the cellular mechanism(s) underlying the aggregation process is poorly understood, although cell motility is generally considered to be an essential phenomenon. In this article we provide the first study investigating the relationship between hepatocyte aggregation and motility behavior on various extracellular matrix substrata, including Matrigel, laminin, and fibronectin. We find that the extent of aggregation depends on the concentration of the extracellular matrix proteins, as well as on the type. Furthermore, we find that the extent of aggregation appears to be independent of classical single-cell locomotion. In fact, under conditions giving rise to substantial aggregation, the fraction of cells exhibiting classical locomotion is essentially negligible. Instead, aggregation appears to involve intracellular contacts accomplished via a different form of cell motility: active cell membrane extensions followed by adhesive cell-cell interactions. An implication of these findings is that aggregation may be largely governed by relative strengths of cell-cell versus cell-substratum interactions. These observations could be helpful for improved design of cell transplantation devices and cell culture substrata. (c) 1996 by John Wiley & Sons, Inc.

Posterior occipitoatlantal hypermobility in Down syndrome: an analysis of 199 patients.

We endeavored to determine the prevalence of occipitoatlantal hypermobility in individuals with Down syndrome, to establish objective radiographic criteria for this entity, and to correlate this with neurologic abnormality. In a retrospective analysis, upper cervical spine radiographs of 210 patients with Down syndrome were compared with those of 102 normal individuals. Radiographs were evaluated using the Powers ratio. Patients identified with radiographic evidence of posterior occipitoatlantal hypermobility were then examined clinically and compared with a matched group of patients with Down syndrome and normal Powers ratios. Of the patients with Down syndrome, 8.5% had a Powers ratio of < 0.55, which was indicative of posterior occipitoatlantal hypermobility (POAH). Furthermore, 66% of those with an abnormal Powers ratio had positive neurologic findings upon physical exam, a finding that was statistically significant when compared to a matched group of patients with Down syndrome and normal Powers ratio.

Quality of life of hemodialysis patients.

The purpose of this study was to assess the quality of life of hemodialysis patients. The sample (n = 349) was selected randomly from the adult, inunit hemodialysis patient population of 90% of the counties of Illinois, with the exception of those dialyzed by the Veterans Administration. The findings indicate that the patients in this study were satisfied with their lives in general. Nevertheless, the results also indicated that continued efforts are needed to improve the health and financial independence of hemodialysis patients.

Needs of family members of intensive care unit patients.

To identify important needs of families of critically ill patients, and the degree to which these needs were being met, 64 family members and 58 nurses were asked to complete a modified version of the Critical Care Family Needs Inventory (Molter & Leske, 1983). Family members and nurses identified many similar important needs, such as the need to have questions answered honestly, the need to be called at home about changes in the patient's condition, and the need to know why things were done for the patient. However, family members indicated that some needs were both more important and less satisfactorily met than the nurses perceived: the need to know the occupational identity of staff members, directions as to what to do at the patient's bedside, and having friends for support.

Psychometric assessment of the Quality of Life Index.

The purpose of this study was to examine the psychometric properties of the Quality of Life Index (QLI) (Ferrans & Powers, 1985a). The sample consisted of 349 patients selected randomly from the adult, in-unit hemodialysis patient population of Illinois. Factor analysis was used to examine the underlying factor structure. A four-factors solution best fit the data, indicating that there were four dimensions underlying the QLI: health and functioning, socioeconomic, psychological/spiritual, and family. Factor analysis of the four primary factors revealed one higher order factor, representing quality of life. Construct validity also was supported by the contrasted groups approach. As predicted, it was found that those who had higher incomes had significantly higher quality of life scores on the social and economic subscale. Support for convergent validity was provided by a strong correlation (r = .77) between scores from the QLI and an assessment of life satisfaction. Findings supported the internal consistency reliability of the entire QLI (alpha = .93) and the four subscales (alphas = .87, .82, .90, .77).

Development of an instrument to measure hope.

The purpose of this study was to develop an instrument to measure hope in adults and to evaluate its psychometric properties. A 40-item Miller Hope Scale (MHS) was developed based on critical elements of hope revealed in a comprehensive review of the literature and on an exploratory study of hope in persons who survived a critical illness. The instrument was critiqued by measurement and content experts, and content validity was established. The MHS was pretested on 75 subjects. The refined instrument was next evaluated using 522 healthy adults. The intent was to establish norms on the instrument before using it on ill subjects. The range of scores on the MHS is 40 to 200, with high scores indicating high hope. Mean hope score for this healthy sample was 164.46 (SD = 16.31). A leptokurtic curve, skewed to the left, was noted in these responses. As expected, the instrument detected high hope in individuals who were screened to have no physical or mental health problems. The internal consistency alpha coefficient was .93 with a 2-week test-retest reliability of .82. Criterion-related construct validity was established by correlating the MHS to the Psychological Well-Being Scale, r = .71, the Existential Well-Being Scale, r = .82, and a 1-item hope self-assessment, r = .69. Divergent validity with the Hopelessness Scale was established, r = -.54. Maximum likelihood factor analysis with oblimin rotation resulted in a three-factor solution: I, Satisfaction with Self, Others, and Life; II, Avoidance of Hope Threats; and III, Anticipation of a Future.

Satisfaction with health care of hemodialysis patients.

The purpose of this study was to assess the satisfaction with care of hemodialysis patients, and to explore the relationships between satisfaction with care, quality of life, and background variables. The sample (n = 416) was randomly selected from the adult, in-unit hemodialysis patient population of a north central state. Overall, patients were satisfied with their care (M = 5.04, range = 1 to 6). An ANOVA demonstrated that patients were most satisfied with physician related aspects of care, followed by nursing/dialysis treatment aspects, and least satisfied with financial/transportation aspects (F(2,830) =28.44. p less than .0001). Overall satisfaction with care was most highly correlated with satisfaction with medical (r = .74) and nursing care (r = .74). Satisfaction with care was moderately correlated with quality of life (r = .42) and satisfaction with health and functioning (r = .42). Somewhat weaker relationships were found between satisfaction with care and socioeconomic aspects of life (r = .31), psychological/spiritual aspects (r = .32), and family (r = .27). Patients who had been on dialysis for a shorter length of time or who had less education were more satisfied with care.

Profile of the well-controlled, well-adjusted hypertensive patient.

The study purpose was to identify discriminant predictors of blood pressure control and adjustment to chronic illness in 450 hypertensive patients. Hypertension control was determined by physician judgment, and adjustment was assessed by Derogatis' (1977) Psychosocial Adjustment to Illness Scale. Potential predictors of the outcome variables were measured by structured interview, formal instruments, and chart review. Well-controlled hypertensive patients had better health adjustment scores, reported more illness-related job problems and less illness-related sexual problems, were more satisfied with health care, knew what to do about medication side effects, were on medications longer, and had lower blood pressure readings on chart review. Well-adjusted hypertensive patients had fewer hypertension-related problems; had their blood pressure under control; were less likely to eat, smoke, or use drugs to handle tension; had no recent weight gain; knew what to do about medication side effects and that there is no cure for hypertension; were less pessimistic and less likely to worry; rated their stress level lower and their quality of life higher; felt that their health was under their own control; tried to problem solve when coping with stress; were on hypertensive medications a shorter time and on fewer medications overall; did not like to be alone when feeling stressed; and ate fewer high sodium foods.

Stressors associated with coronary bypass surgery.

The purpose of this study was to: design and test an instrument to evaluate the incidence and severity of stressors associated with coronary bypass surgery and assess the concordance between patient and nurse perceptions of such stressors. The patient sample consisted of 30 patients recovering without complications from coronary bypass surgery. Patients were white, primarily male and employed, one-third with graduate education, with a mean age of 54. The nurse sample consisted of 18 registered nurses with cardiosurgical nursing care experience. A 30-item stressor scale was developed: 27 items were derived from literature review and 3 from comments of cardiovascular clinical specialists. Stressfulness of each item was rated on a 5-point scale. A pilot study with seven patients provided information for initial scale refinement. Content validity of the scale has both theoretical and empirical support because of the varied sources used to obtain and validate relevant items for the tool. Homogeneity reliability of the scale was supported by high coefficient alphas. Based on severity of stress ratings, two-way analysis of variance indicated that the cardiothoracic nurses generally rated all items as significantly more stressful for coronary bypass patients than did the patients themselves. Comparisons used by the nurses and the patients in assigning stressfulness ratings are discussed.

Influence of weather on osteoarthritics.

This exploratory study examined the effects of selected weather variables on pain and pain-related stress in osteoarthritic subjects. Urban and rural dwelling arthritics who perceived that weather made their symptoms worse and those who did not were surveyed. Some persons with osteoarthritis in urban Chicago were more weather sensitive than their rural counterparts in Grand Forks, North Dakota. Multiple regression analysis showed that precipitation affected degree of pain for urban subjects who identified weather as a pain-generating factor; barometric pressure, relative humidity and sunshine were significant factors influencing pain-related stress. Wind speed correlated with pain and pain-related stress; relative humidity and precipitation correlated with pain-related stress for urban subjects who did not perceive weather as a problem. Specific weather variables were not identified as affecting rural subjects' pain. However, temperature and barometric pressure affected degree of pain-related stress in rural subjects who perceived weather as a problem. Subtle differences between Chicago urban and Grand Forks rural climates are reflected in arthritic subjects' degree of pain and their perception of pain-related stress.

Psychometric evaluation of the Hemodialysis Stressor Scale.

This report updates the psychometric information available on the Hemodialysis Stressor Scale. The tool is a 29-item scale that rates the incidence and severity of stressors associated with hemodialysis treatment of end-stage renal disease. Six items are classified as physiologic stressors and 23 as psychosocial stressors. Alpha homogeneity coefficients achieved acceptable standards for reliability. Content validity is demonstrated by the varied sources used to ascertain pertinent items for the scale. Construct validity of the scale was investigated by factor analysis (N = 174). A two-factor solution to evaluate the validity of the physiological-psychosocial dichotomy showed insufficient support for this simplistic dichotomous classification of hemodialysis stressors. A subsequent unrestricted factor solution to explore the multidimensionality of the scale yielded eight factors, but only three were significant, so a three-factor solution was subjected to rotation. The content of the 6 physiological and 9 psychosocial items loading significantly on Factor I characterized this factor as psychobiological; Factor II consisted of 12 psychological and social stressors; Factor III pertained to 8 dependency and restriction stressors. The three-factor solution was seen as the best-fitting solution with this particular data set because it was conceptually clear, informative, and parsimonious.