Showing papers by "Tulane University published in 2001"
TL;DR: In this paper, first-principles based calculations of the tunneling conductance and magnetoconductance of epitaxial ''mathrm{Fe}(100)|\mathm{MgO''(100), ''mgO''.
Abstract: We present first-principles based calculations of the tunneling conductance and magnetoconductance of epitaxial $\mathrm{Fe}(100)|\mathrm{MgO}(100)|\mathrm{Fe}(100)$ sandwiches. Our results indicate that tunneling is much more interesting and complicated than the simple barrier model used previously. We obtain the following general results: (1) Tunneling conductance depends strongly on the symmetry of the Bloch states in the electrodes and of the evanescent states in the barrier layer. (2) Bloch states of different symmetry decay at different rates within the barrier. The decay rate is determined by the complex energy bands of the same symmetry in the barrier. (3) There may be quantum interference between the decaying states in the barrier. This leads to an oscillatory dependence of the tunneling current on ${k}_{\ensuremath{\Vert}}$ and a damped oscillatory dependence on barrier thickness. (4) Interfacial resonance states can allow particular Bloch states to tunnel efficiently through the barrier. For $\mathrm{Fe}(100)|\mathrm{MgO}(100)|\mathrm{Fe}(100)$ our calculations indicate that quite different tunneling mechanisms dominate the conductance in the two spin channels. In the majority channel the conductance is primarily via Bloch electrons with small transverse momentum. One particular state with ${\ensuremath{\Delta}}_{1}$ symmetry is able to effectively couple from the Fe into the MgO. In the minority channel the conductance is primarily through interface resonance states especially for thinner layers. We predict a large magnetoresistance that increases with barrier thickness.
1,823 citations
TL;DR: Because normal-weight children who become obese adults have adverse risk factor levels and probably will be at increased risk for adult morbidity, the results emphasize the need for both primary and secondary prevention.
Abstract: Background. Childhood obesity is related to adult levels of lipids, lipoproteins, blood pressure, and insulin and to morbidity from coronary heart disease (CHD). However, the importance of the age at which obesity develops in these associations remains uncertain. Objective and Design. We assessed the longitudinal relationship of childhood body mass index (BMI, kg/m2) to adult levels of lipids, insulin, and blood pressure among 2617 participants. All participants were initially examined at ages 2 to 17 years and were reexamined at ages 18 to 37 years; the mean follow-up was 17 years. Results. Of the overweight children (BMI ≥95th percentile), 77% remained obese (≥30 kg/m2) as adults. Childhood overweight was related to adverse risk factor levels among adults, but associations were weak (r ∼ 0.1–0.3) and were attributable to the strong persistence of weight status between childhood and adulthood. Although obese adults had adverse levels of lipids, insulin, and blood pressure, levels of these risk factors did not vary with childhood weight status or with the age (≤8 years, 12–17 years, or ≥18 years) of obesity onset. Conclusions. Additional data are needed to assess the independent relationship of childhood weight status to CHD morbidity. Because normal-weight children who become obese adults have adverse risk factor levels and probably will be at increased risk for adult morbidity, our results emphasize the need for both primary and secondary prevention.
1,384 citations
TL;DR: An algorithm is developed that both clears the financial system in a computationally efficient fashion and provides information on the systemic risk faced by the individual system firms and produces qualitative comparative statics for financial systems.
Abstract: We consider default by firms that are part of a single clearing mechanism. The obligations of all firms within the system are determined simultaneously in a fashion consistent with the priority of debt claims and the limited liability of equity. We first show, via a fixed-point argument, that there always exists a "clearing payment vector" that clears the obligations of the members of the clearing system; under mild regularity conditions, this clearing vector is unique. Next, we develop an algorithm that both clears the financial system in a computationally efficient fashion and provides information on the systemic risk faced by the individual system firms. Finally, we produce qualitative comparative statics for financial systems. These comparative statics imply that, in contrast to single-firm results, even unsystematic, nondissipative shocks to the system will lower the total value of the system and may lower the value of the equity of some of the individual system firms.
1,261 citations
TL;DR: Male sex, less education, physical inactivity, cigarette smoking, overweight, diabetes, hypertension, valvular heart disease, and coronary heart disease are all independent risk factors for CHF.
Abstract: Background: The incidence of congestive heart failure (CHF) has been increasing steadily in the United States during the past 2 decades. We studied risk factors for CHF and their corresponding attributable risk in the First National Health and Nutrition Examination Survey Epidemiologic Follow-up Study. Participants and Methods: A total of 13643 men and women without a history of CHF at baseline examination were included in this prospective cohort study. Risk factors were measured using standard methods between 1971 and 1975. Incidence of CHF was assessed using medical records and death certificates obtained between 1982 and 1984 and in 1986, 1987, and 1992. Results: During average follow-up of 19 years, 1382 CHF cases were documented. Incidence of CHF was positively and significantly associated with male sex (relative risk [RR], 1.24; 95% confidence interval [CI], 1.10-1.39; P,.001; population attributable risk [PAR], 8.9%), less than a high school education (RR, 1.22; 95% CI, 1.04-1.42; P=.01; PAR, 8.9%), low physical activity (RR, 1.23; 95% CI, 1.09-1.38; P,.001; PAR, 9.2%), cigarette smoking (RR, 1.59; 95% CI, 1.39-1.83; P,.001; PAR, 17.1%), overweight (RR, 1.30; 95% CI, 1.12-1.52; P=.001; PAR, 8.0%), hypertension (RR, 1.40; 95% CI, 1.241.59; P,.001; PAR, 10.1%), diabetes (RR, 1.85; 95% CI, 1.51-2.28; P,.001; PAR, 3.1%), valvular heart disease (RR, 1.46; 95% CI, 1.17-1.82; P=.001; PAR, 2.2%), and coronary heart disease (RR, 8.11; 95% CI, 6.95-9.46; P,.001; PAR, 61.6%). Conclusions: Male sex, less education, physical inactivity, cigarette smoking, overweight, diabetes, hypertension, valvular heart disease, and coronary heart disease are all independent risk factors for CHF. More than 60% of the CHF that occurs in the US general population might be attributable to coronary heart disease. Arch Intern Med. 2001;161:996-1002
1,134 citations
TL;DR: It is found that early colonies of marrow stromal cells contain a third kind of cell: very small round cells that rapidly self-renew and have a greater potential for multipotential differentiation than samples enriched for the large cells.
Abstract: Marrow stromal cells are adult stem cells from bone marrow that can differentiate into multiple nonhematopoietic cell lineages. Previous reports demonstrated that single-cell-derived colonies of marrow stromal cells contained two morphologically distinct cell types: spindle-shaped cells and large flat cells. Here we found that early colonies also contain a third kind of cell: very small round cells that rapidly self-renew. Samples enriched for the small cells had a greater potential for multipotential differentiation than samples enriched for the large cells. Also, the small cells expressed a series of surface epitopes and other proteins that potentially can be used to distinguish the small cells from the large cells. The results suggested it will be important to distinguish the major subpopulations of marrow stromal cells in defining their biology and their potential for cell and gene therapy.
932 citations
TL;DR: In this article, the authors consider the accuracy of projection method approximations to the initial-boundary-value problem for the incompressible Navier-Stokes equations and present an improved projection algorithm which is fully second-order accurate.
841 citations
TL;DR: It is suggested that alcohol reduction should be recommended as an important component of lifestyle modification for the prevention and treatment of hypertension among heavy drinkers.
Abstract: Alcohol drinking has been associated with increased blood pressure in epidemiological studies. We conducted a meta-analysis of randomized controlled trials to assess the effects of alcohol reductio...
737 citations
TL;DR: It is shown that passive intravenous transfer of the human neutralizing monoclonal antibody b12 provides dose-dependent protection to macaques vaginally challenged with the R5 virus SHIV162P4, suggesting that a vaccine based on antibody alone would need to sustain serum neutralizing antibody titers of the order of 1:400 to achieve sterile protection but that lower titers, around 1:100, could provide a significant benefit.
Abstract: A major unknown in human immunodeficiency virus (HIV-1) vaccine design is the efficacy of antibodies in preventing mucosal transmission of R5 viruses. These viruses, which use CCR5 as a coreceptor, appear to have a selective advantage in transmission of HIV-1 in humans. Hence R5 viruses predominate during primary infection and persist throughout the course of disease in most infected people. Vaginal challenge of macaques with chimeric simian/human immunodeficiency viruses (SHIV) is perhaps one of the best available animal models for human HIV-1 infection. Passive transfer studies are widely used to establish the conditions for antibody protection against viral challenge. Here we show that passive intravenous transfer of the human neutralizing monoclonal antibody b12 provides dose-dependent protection to macaques vaginally challenged with the R5 virus SHIV(162P4). Four of four monkeys given 25 mg of b12 per kg of body weight 6 h prior to challenge showed no evidence of viral infection (sterile protection). Two of four monkeys given 5 mg of b12/kg were similarly protected, whereas the other two showed significantly reduced and delayed plasma viremia compared to control animals. In contrast, all four monkeys treated with a dose of 1 mg/kg became infected with viremia levels close to those for control animals. Antibody b12 serum concentrations at the time of virus challenge corresponded to approximately 400 (25 mg/kg), 80 (5 mg/kg), and 16 (1 mg/kg) times the in vitro (90%) neutralization titers. Therefore, complete protection against mucosal challenge with an R5 SHIV required essentially complete neutralization of the infecting virus. This suggests that a vaccine based on antibody alone would need to sustain serum neutralizing antibody titers (90%) of the order of 1:400 to achieve sterile protection but that lower titers, around 1:100, could provide a significant benefit. The significance of such substerilizing neutralizing antibody titers in the context of a potent cellular immune response is an important area for further study.
696 citations
TL;DR: It is shown that malignant human ovarian epithelial tumor cells express very high levels of stromal-derived factor-1, which induces DC2 precursor (preDC2) chemotaxis and adhesion/transmigration, upregulates preDC2 very late antigen (VLA)-5, and protects preDC1s from tumor macrophage interleukin-10–induced apoptosis, all through CXC chemokine receptor-4.
Abstract: Dendritic-cell (DC) trafficking and function in tumors is poorly characterized, with studies confined to myeloid DCs (DC1s). Tumors inhibit DC1 migration and function, likely hindering specific immunity. The role of plasmacytoid DCs (DC2s) in tumor immunity is unknown. We show here that malignant human ovarian epithelial tumor cells express very high levels of stromal-derived factor-1, which induces DC2 precursor (preDC2) chemotaxis and adhesion/transmigration, upregulates preDC2 very late antigen (VLA)-5, and protects preDC2s from tumor macrophage interleukin-10-induced apoptosis, all through CXC chemokine receptor-4. The VLA-5 ligand vascular-cell adhesion molecule-1 mediated preDC2 adhesion/transmigration. Tumor preDC2s induced significant T-cell interleukin-10 unrelated to preDC2 differentiation or activation state, and this contributed to poor T-cell activation. Myeloid precursor DCs (preDC1s) were not detected. Tumors may weaken immunity by attracting preDC2s and protecting them from the harsh microenvironment, and by altering preDC1 distribution.
649 citations
TL;DR: Experiments addressing the concept of gene imprinting or induction of epigenetic memory by estrogen or other hormones suggest a link to persistent, heritable phenotypic changes seen after developmental estrogenization, independent of mutagenesis.
Abstract: The term "endocrine disrupting chemicals" is commonly used to describe environmental agents that alter the endocrine system. Laboratories working in this emerging field-environmental endocrine research-have looked at chemicals that mimic or block endogenous vertebrate steroid hormones by interacting with the hormone's receptor. Environmental chemicals known to do this do so most often with receptors derived from the steroid/thyroid/retinoid gene family. They include ubiquitous and persistent organochlorines, as well as plasticizers, pharmaceuticals, and natural hormones. These chemicals function as estrogens, antiestrogens, and antiandrogens but have few, if any, structural similarities. Therefore, receptor-based or functional assays have the best chance of detecting putative biological activity of environmental chemicals. Three nuclear estrogen receptor forms-alpha, beta, and gamma-as well as multiple membrane forms and a possible mitochondrial form have been reported, suggesting a previously unknown diversity of signaling pathways available to estrogenic chemicals. Examples of environmental or ambient estrogenization occur in laboratory experiments, zoo animals, domestic animals, wildlife, and humans. Environmentally estrogenized phenotypes may differ depending upon the time of exposure-i.e., whether the exposure occurred at a developmental (organizational and irreversible) or postdevelopmental (activational and reversible) stage. The term "estrogen" must be defined in each case, since steroidal estrogens differ among themselves and from synthetic or plant-derived chemicals. An "estrogen-like function" seems to be an evolutionarily ancient signal that has been retained in a number of chemicals, some of which are vertebrate hormones. Signaling, required for symbiosis between plants and bacteria, may be viewed, therefore, as an early example of hormone cross-talk. Developmental feminization at the structural or functional level is an emerging theme in species exposed, during embryonic or fetal life, to estrogenic compounds. Human experience as well as studies in experimental animals with the potent estrogen diethylstilbestrol provide informative models. Advances in the molecular genetics of sex differentiation in vertebrates facilitate mechanistic understanding. Experiments addressing the concept of gene imprinting or induction of epigenetic memory by estrogen or other hormones suggest a link to persistent, heritable phenotypic changes seen after developmental estrogenization, independent of mutagenesis. Environmental endocrine science provides a new context in which to examine the informational content of ecosystem-wide communication networks. As common features come to light, this research may allow us to predict environmentally induced alterations in internal signaling systems of vertebrates and some invertebrates and eventually to explicate environmental contributions to human reproductive and developmental health.
TL;DR: Assessment of oxidative stress status (OSS) may help in designing newer modes of male factor infertility treatment by suitable antioxidants because a balance between ROS generation and antioxidant capacity plays a critical role in the pathophysiology of disease state.
Abstract: Impairment of normal spermatogenesis and sperm function are the most common causes of male factor infertility. Abnormal sperm function is difficult to evaluate and treat. There is a lack of understanding of the factors contributing to normal and abnormal sperm function leading to infertility. Many recent studies indicate that oxygen-derived free radicals induce damage to spermatozoa. The excessive generation of these reactive oxygen species (superoxide, hydroxyl, nitric oxide, peroxide, peroxynitrile) by immature and abnormal spermatozoa and by contaminating leukocytes associated with genitourinary tract inflammation have been identified with idiopathic male infertility. Mammalian spermatozoa membranes are rich in polyunsaturated fatty acids. This makes them very susceptible to oxygen-induced damage, which is mediated by lipid peroxidation. In a normal situation, the antioxidant mechanisms present in the reproductive tissues and their secretions are likely to quench these reactive oxygen species (ROS) and protect against oxidative damage to gonadal cells and mature spermatozoa. During chronic disease states, aging, toxin exposure, or genitourinary infection/inflammation, these cellular antioxidant mechanisms downplay and create a situation called oxidative stress. Thus, a balance between ROS generation and antioxidant capacity plays a critical role in the pathophysiology of disease state. Recent efforts towards the development of new reliable assays to evaluate this oxidative stress status have resulted in the establishment of ROS-TAC score. Such assessment of oxidative stress status (OSS) may help in designing newer modes of male factor infertility treatment by suitable antioxidants.
TL;DR: The prevalence of overweight has increased approximately twofold in the 20-year period from 1974 to 1994, with the largest increases observed among 19- to 24-year-olds, and the annual increases in weight and obesity that occurred from 1983 to 1994 were 50% higher than those from 1973 to 1982.
Abstract: Obesity among children has reached epidemic proportions. Today, an estimated one in four children in the United States is overweight. while 11% arc obese. Children who are overweight tend to remain so up to 20 years of age; in general, they have a 1.5- to twofold higher risk for becoming overweight as adults. The prevalence of overweight has increased approximately twofold in the 20-year period from 1974 to 1994, with the largest increases observed among 19- to 24-year-olds. The annual increases in weight and obesity that occurred from 1983 to 1994 were 50% higher than those from 1973 to 1982. Overweight youth are 2.4 times as likely to have a high serum total cholesterol level, and 43.5 times as likely to have three cardiovascular risk factors. Although the total energy intake of children has remained the same, and the macronutrient density of the diet has changed, the percentage of energy from fat has decreased, while that from carbohydrates and protein has increased. Children have been consuming lower amounts of fats/oils, vegetables/soups, breads/grains, mixed meats, desserts, candy, and eggs. and increasing amounts of fruits/fruit juices, beverages. poultry, snacks, condiments, and cheese. Changes in specific eating patterns may explain the increase in adiposity among children; e.g., increases have occurred in the number of meals eaten at restaurants, food availability, portion sizes, snacking and meal-skipping. Successful prevention and treatment of obesity in childhood could reduce the adult incidence of cardiovascular disease. Because substantial weight loss is difficult to maintain, the prevention of obesity by promoting healthier lifestyles should be one of our highest priorities in the new millennium.
TL;DR: All patients undergoing cruciate-retaining primary total knee arthroplasty for degenerative osteoarthritis at one center were studied prospectively and component malrotation is a significant factor in the development of anterior knee pain after total knee ligation.
Abstract: All patients undergoing cruciate-retaining primary total knee arthroplasty for degenerative osteoarthritis at one center were studied prospectively. Clinical and radiographic followup was obtained at a minimum 5 years in 102 knees in 73 patients. Patients were asked specifically about the presence of the pain in the anterior aspect of the knee in the vicinity of the patella and rated the severity of the pain on a visual analog scale. Significant anterior knee pain rating at least 3 of 10 on the visual analog scale was present in 16 knees (13 patients). Eleven patients with 14 symptomatic knees agreed to undergo computed tomography scanning to accurately determine the rotation of the tibial and femoral components. The epicondylar axis and tibial tubercle were used as references using a previously validated technique. A control group of 11 asymptomatic patients (14 knees), matched for age, gender, and length of followup also underwent computed tomography scanning. All patients in both groups had normal axial alignment. There was a highly significant difference in tibial component rotation between the two groups with the patients with anterior knee pain averaging 6.2 degrees internal rotation compared with 0.4 degrees external rotation in the control group. There also was a significant difference in combined component rotation with the patients with anterior knee pain averaging 4.7 degrees internal rotation compared with 2.6 degrees external rotation in the control group. There was no significant difference in the degree of radiographic patellar tilt or patellar subluxation between the two groups. Patients with combined component internal rotation were more than five times as likely to experience anterior knee pain after total knee arthroplasty compared with those with combined component external rotation. Component malrotation is a significant factor in the development of anterior knee pain after total knee arthroplasty.
TL;DR: The data suggested that the hMSCs may have been differentiated into early progenitors of neural cells in vitro under conditions that increase the intracellular level of cAMP.
TL;DR: The self-assembly of conjugated polymer/silica nanocomposite films with hexagonal, cubic or lamellar mesoscopic order using polymerizable amphiphilic diacetylene molecules as both structure-directing agents and monomers is reported.
Abstract: Nature abounds with intricate composite architectures composed of hard and soft materials synergistically intertwined to provide both useful functionality and mechanical integrity. Recent synthetic efforts to mimic such natural designs have focused on nanocomposites, prepared mainly by slow procedures like monomer or polymer infiltration of inorganic nanostructures or sequential deposition. Here we report the self-assembly of conjugated polymer/silica nanocomposite films with hexagonal, cubic or lamellar mesoscopic order using polymerizable amphiphilic diacetylene molecules as both structure-directing agents and monomers. The self-assembly procedure is rapid and incorporates the organic monomers uniformly within a highly ordered, inorganic environment. Polymerization results in polydiacetylene/silica nanocomposites that are optically transparent and mechanically robust. Compared to ordered diacetylene-containing films prepared as Langmuir monolayers or by Langmuir-Blodgett deposition, the nanostructured inorganic host alters the diacetylene polymerization behaviour, and the resulting nanocomposite exhibits unusual chromatic changes in response to thermal, mechanical and chemical stimuli. The inorganic framework serves to protect, stabilize, and orient the polymer, and to mediate its function. The nanocomposite architecture also provides sufficient mechanical integrity to enable integration into devices and microsystems.
TL;DR: It is concluded that EHYP is associated with marked cellular changes over time within neural regions associated with cognitive functions and may underlie components of the learning and memory impairments found in OSA.
Abstract: The role played by chronic episodic hypoxia (EHYP) in the neurocognitive morbidity of obstructive sleep apnea (OSA) is unknown. Sleep recordings, Morris water maze experiments, and immunohistochemistry for NMDA NR1 glutamate receptor, c-fos protein, and apoptosis [nuclear immunoreactivity for single-stranded DNA and terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling assay] were conducted in EHYP-exposed Sprague Dawley male rats. Exposures consisted of up to14 d in an environmental chamber in which O(2) concentrations were cycled between 10 and 21% every 90 sec or 30 min during 12 hr of daylight. For the remaining 12 hr, EHYP rats breathed room air, while controls spent 14 d in room air. Although EHYP induced significant disruption of sleep architecture during the initial day of exposure, sleep patterns normalized thereafter. Marked increases in apoptosis occurred in the CA1 hippocampal region (sevenfold) and cortex (Cx; eightfold) after 1-2 d of EHYP but not in CA3 and were followed by decreases toward normoxic levels by 14 d. Double labeling for NMDA NR1 and c-fos revealed marked architectural disorganization in CA1 and Cx with increases in c-fos over time. Rats exposed to EHYP displayed significantly longer escape latencies and swim path lengths to escape a hidden platform during 12 training trials given over 2 d. Differences in the performances of EHYP and control rats, although reduced, persisted after 14 d of recovery. We conclude that EHYP is associated with marked cellular changes over time within neural regions associated with cognitive functions. Furthermore, EHYP impaired performance during acquisition of a cognitive spatial task without affecting sensorimotor function. Such changes may underlie components of the learning and memory impairments found in OSA.
TL;DR: A theoretical framework supporting experimental measures of dynamic properties of human EEG is proposed with emphasis on distinct alpha rhythms, and new EEG data demonstrate that both globally coherent and locally dominated behavior can occur within the alpha band, depending on narrow band frequency, spatial measurement scale, and brain state.
Abstract: A theoretical framework supporting experimental measures of dynamic properties of human EEG is proposed with emphasis on distinct alpha rhythms. Robust relationships between measured dynamics and cognitive or behavioral conditions are reviewed, and proposed physiological bases for EEG at cellular levels are considered. Classical EEG data are interpreted in the context of a conceptual framework that distinguishes between locally and globally dominated dynamic processes, as estimated with coherence or other measures of phase synchronization. Macroscopic (scalp) potentials generated by cortical current sources are described at three spatial scales, taking advantage of the columnar structure of neocortex. New EEG data demonstrate that both globally coherent and locally dominated behavior can occur within the alpha band, depending on narrow band frequency, spatial measurement scale, and brain state. Quasi-stable alpha phase structures consistent with global standing waves are observed. At the same time, alpha and theta phase locking between cortical regions during mental calculations is demonstrated, consistent with neural network formation. The brain-binding problem is considered in the context of EEG dynamic behavior that generally exhibits both of these local and global aspects. But specific experimental designs and data analysis methods may severely bias physiological interpretations in either local or global directions.
TL;DR: In this article, the authors discuss general issues with respect to multivariate normality, indicators of latent products, and identification problems in MSEMs, and illustrate techniques that are available for the testing of interaction effects in structural equation models.
Abstract: The concomitant proliferation of causal modeling and hypotheses of multiplicative effects has brought about a tremendous need for procedures that allow the testing of moderated structural equation models (MSEMs). The seminal work of Kenny and Judd and Hayduk has been drawn on by several authors in the past 10 years, thus producing procedures that allow for such tests. Yet, utilization of MSEMs in empirical research has been quite rare. The purposes of this article are twofold. First, the authors discuss general issues with respect to multivariate normality, indicators of latent products, the nature of latent products, and identification problems in MSEM. Second, they review and illustrate techniques that are available for the testing of interaction effects in structural equation models.
TL;DR: A model of the parental/family variables as moderators and vicarious traumatic agents for symptoms in young children is presented, and a Compound Model is proposed, with three distinctive patterns of the parent–child relationship that impact on posttraumatic symptomatology in youngChildren.
Abstract: This paper describes the clinical and research evidence for the importance of the relational context of posttraumatic stress disorder in young children. We review 17 studies that simultaneously assessed parental and child functioning following trauma. In many studies, despite limitations, an association between undesirable parental/family variables and maladaptive child outcomes has been consistently found. We present a model of the parental/family variables as moderators and vicarious traumatic agents for symptoms in young children. Also, a Compound Model is proposed, with three distinctive patterns of the parent–child relationship that impact on posttraumatic symptomatology in young children. Implications for clinical practice and research directions are discussed.
TL;DR: An AIDS vaccine based on attenuated VSV vectors expressing env and gag genes and tested it in rhesus monkeys, finding protection from AIDS was highly significant.
TL;DR: It is argued that for the study of adaptation to proceed, greater integration of laboratory studies of performance and behavioral/ecological studies is needed, and this approach is illustrated by examining two questions: how does the environment affect locomotor function in nature and what percentage of locomotor capacities do animals use in nature.
Abstract: ▪ Abstract Understanding adaptation in morphological and physiological traits requires elucidation of how traits relate to whole-organism performance and how performance relates to fitness. A common assumption is that performance capacities are utilized by and important to organisms. For some systems, it is assumed that high levels of physical fitness, as indexed by measures of locomotor performance, lead to high fitness levels. Although biologists have appreciated this, little attention has been paid to quantifying how organisms use their performance capacities in nature. We argue that for the study of adaptation to proceed, greater integration of laboratory studies of performance and behavioral/ecological studies is needed, and we illustrate this approach by examining two questions. First, how does the environment affect locomotor function in nature? Second, what percentage of locomotor capacities do animals use in nature? A review of studies in several animal groups shows widespread effects of the envi...
TL;DR: The discipline of suspension culture needs a systematic analysis of the relationship between mechanical culture conditions and biological effects, emphasizing cellular processes important for the industrial production of biological pharmaceuticals and devices.
Abstract: Suspension culture remains a popular modality, which manipulates mechanical culture conditions to maintain the specialized features of cultured cells. The rotating-wall vessel is a suspension culture vessel optimized to produce laminar flow and minimize the mechanical stresses on cell aggregates in culture. This review summarizes the engineering principles, which allow optimal suspension culture conditions to be established, and the boundary conditions, which limit this process. We suggest that to minimize mechanical damage and optimize differentiation of cultured cells, suspension culture should be performed in a solid-body rotation Couette-flow, zero-headspace culture vessel such as the rotating-wall vessel. This provides fluid dynamic operating principles characterized by 1) solid body rotation about a horizontal axis, characterized by colocalization of cells and aggregates of different sedimentation rates, optimally reduced fluid shear and turbulence, and three-dimensional spatial freedom; and 2) oxygenation by diffusion. Optimization of suspension culture is achieved by applying three tradeoffs. First, terminal velocity should be minimized by choosing microcarrier beads and culture media as close in density as possible. Next, rotation in the rotating-wall vessel induces both Coriolis and centrifugal forces, directly dependent on terminal velocity and minimized as terminal velocity is minimized. Last, mass transport of nutrients to a cell in suspension culture depends on both terminal velocity and diffusion of nutrients. In the transduction of mechanical culture conditions into cellular effects, several lines of evidence support a role for multiple molecular mechanisms. These include effects of shear stress, changes in cell cycle and cell death pathways, and upstream regulation of secondary messengers such as protein kinase C. The discipline of suspension culture needs a systematic analysis of the relationship between mechanical culture conditions and biological effects, emphasizing cellular processes important for the industrial production of biological pharmaceuticals and devices.
TL;DR: A novel application of principal components analysis (spatiotemporal PCA) was used to decompose the event-related brain potentials obtained with a dense electrode array, with the purpose of elucidating the late ERP components elicited by deviant stimuli under "attend" and "ignore" conditions.
Abstract: We used a novel application of principal components analysis (spatiotemporal PCA) to decompose the event-related brain potentials (ERPs) obtained with a dense electrode array, with the purpose of elucidating the late ERP components elicited by deviant stimuli under “attend” and “ignore” conditions. First, a “spatial” PCA was performed to identify a set of scalp distributions (spatial factors or “virtual electrodes”) that accounted for the spatial variance in the data set. The data were expressed as spatial factor scores or “virtual ERPs” measured at each of the virtual electrodes. These virtual ERPs were submitted to a “temporal” PCA, yielding a set of temporal factors or “virtual epochs.” Statistical analyses of the temporal factor scores found that (1) attended deviant stimuli elicited the P300 and Novelty P3 components, the latter being largest for highly salient nontargets; (2) “ignored” deviants elicited a small Novelty P3, and depending on the primary task, a small P300; and (3) the classical Slow Wave consisted of separate frontal-negative and posterior-positive components.
TL;DR: It is suggested that the endogenous levels and potencies of indirubin and indigo are such that they activate AhR-mediated signaling mechanisms in vivo.
TL;DR: This study indicates a significant inverse relationship between legumes intake and risk of CHD and suggests that increasing legume intake may be an important part of a dietary approach to the primary prevention ofCHD in the general population.
Abstract: Background Soybean protein and dietary fiber supplementation reduce serum cholesterol in randomized controlled trials. Consumption of legumes, which are high in bean protein and water-soluble fiber, may be associated with a reduced risk of coronary heart disease (CHD). Methods A total of 9632 men and women who participated in the First National Health and Nutrition Examination Survey Epidemiologic Follow-up Study (NHEFS) and were free of cardiovascular disease (CVD) at their baseline examination were included in this prospective cohort study. Frequency of legume intake was estimated using a 3-month food frequency questionnaire, and incidence of CHD and CVD was obtained from medical records and death certificates. Results Over an average of 19 years of follow-up, 1802 incident cases of CHD and 3680 incident cases of CVD were documented. Legume consumption was significantly and inversely associated with risk of CHD ( P = .002 for trend) and CVD ( P = .02 for trend) after adjustment for established CVD risk factors. Legume consumption 4 times or more per week compared with less than once a week was associated with a 22% lower risk of CHD (relative risk, 0.78; 95% confidence interval, 0.68-0.90) and an 11% lower risk of CVD (relative risk, 0.89; 95% confidence interval, 0.80-0.98). Conclusions Our study indicates a significant inverse relationship between legume intake and risk of CHD and suggests that increasing legume intake may be an important part of a dietary approach to the primary prevention of CHD in the general population.
TL;DR: Studies of pediatric diarrhea show substantial evidence of clinical benefits from probiotic therapy in patients with viral gastroenteritis, and data on LGG treatment for Clostridium difficile diarrhea appear promising, but data to support use of probiotics for prevention of traveler's diarrhea are more limited.
Abstract: There is an increasing scientific and commercial interest in the use of beneficial microorganisms, or "probiotics," for the prevention and treatment of disease. The microorganisms most frequently used as probiotic agents are lactic-acid bacteria such as Lactobacillus rhamnosus GG (LGG), which has been extensively studied in recent literature. Multiple mechanisms of action have been postulated, including lactose digestion, production of antimicrobial agents, competition for space or nutrients, and immunomodulation. We have reviewed recent studies of probiotics for the treatment and control of infectious diseases. Studies of pediatric diarrhea show substantial evidence of clinical benefits from probiotic therapy in patients with viral gastroenteritis, and data on LGG treatment for Clostridium difficile diarrhea appear promising. However, data to support use of probiotics for prevention of traveler's diarrhea are more limited. New research suggests potential applications in vaccine development and prevention of sexually transmitted diseases. Further studies are needed to take full advantage of this traditional medical approach and to apply it to the infectious diseases of the new millennium.
TL;DR: Evidence is provided of the role of circulating IGF-I as an important component of overall insulin action in peripheral tissues and of the insulin insensitivity seen in the LID mice is muscle specific.
Abstract: Insulin and insulin-like growth factors (IGFs) mediate a variety of signals involved in mammalian development and metabolism. To study the metabolic consequences of IGF-I deficiency, we used the liver IGF-I–deficient (LID) mouse model. The LID mice show a marked reduction (∼75%) in circulating IGF-I and elevated growth hormone (GH) levels. Interestingly, LID mice show a fourfold increase in serum insulin levels (2.2 vs. 0.6 ng/ml in control mice) and abnormal glucose clearance after insulin injection. Fasting blood glucose levels and those after a glucose tolerance test were similar between the LID mice and their control littermates. Thus, the high levels of circulating insulin enable the LID mice to maintain normoglycemia in the presence of apparent insulin insensitivity. Insulin-induced autophosphorylation of the insulin receptor and tyrosine phosphorylation of insulin receptor substrate (IRS)-1 were absent in muscle, but were normal in liver and white adipose tissue of the LID mice. In contrast, IGF-I–induced autophosphorylation of its cognate receptor and phosphorylation of IRS-1 were normal in muscle of LID mice. Thus, the insulin insensitivity seen in the LID mice is muscle specific. Recombinant human IGF-I treatment of the LID mice caused a reduction in insulin levels and an increase in insulin sensitivity. Treatment of the LID mice with GH-releasing hormone antagonist, which reduces GH levels, also increased insulin sensitivity. These data provide evidence of the role of circulating IGF-I as an important component of overall insulin action in peripheral tissues.
TL;DR: The consumption of alcohol in amounts ≥210 g per week is an independent risk factor for hypertension in free-living North American populations and the consumption of low to moderate amounts of alcohol also appears to be associated with a higher risk of hypertension in black men.
Abstract: A close relationship between alcohol consumption and hypertension has been established, but it is unclear whether there is a threshold level for this association. In addition, it has infrequently been studied in longitudinal studies and in black people. In a cohort study, 8334 of the Atherosclerosis Risk in Communities (ARIC) Study participants, aged 45 to 64 years at baseline, who were free of hypertension and coronary heart disease had their blood pressures ascertained after 6 years of follow-up. Alcohol consumption was assessed by dietary interview. The type of alcoholic beverage predominantly consumed was defined by the source of the largest amount of ethanol consumed. Incident hypertension was defined as a systolic blood pressure >/=140 mm Hg or diastolic blood pressure >/=90 mm Hg or use of antihypertensive medication. There was an increased risk of hypertension in those who consumed large amounts of ethanol (>/=210 g per week) compared with those who did not consume alcohol over the 6 years of follow-up. The adjusted odds ratios (95% confidence interval) were 1.2 (0.85 to 1.67) for white men, 2.02 (1.08 to 3.79) for white women, and 2.31 (1.11 to 4.86) for black men. Only 4 black women reported drinking >210 g ethanol per week. At low to moderate levels of alcohol consumption (1 to 209 g per week), the adjusted odds ratios (95% confidence interval) were 0.88 (0.71 to 1.08) in white men, 0.89 (0.73 to 1.09) in white women, 1.71 (1.11 to 2.64) in black men, and 0.88 (0.59 to 1.33) in black women. Systolic and diastolic blood pressures were higher in black men who consumed low to moderate amounts of alcohol compared with the nonconsumers but not in the 3 other race-gender strata. Models with polynomial terms of alcohol exposure suggested a nonlinear association in white and black men. Higher levels of consumption of all types of alcoholic beverages were associated with a higher risk of hypertension for all race-gender strata. The consumption of alcohol in amounts >/=210 g per week is an independent risk factor for hypertension in free-living North American populations. The consumption of low to moderate amounts of alcohol also appears to be associated with a higher risk of hypertension in black men.
TL;DR: This study represents the first extensive gene expression analysis of MSCs and reveals new insight into the biology, ontogeny, and in vivo function of the cells.
Abstract: Mesenchymal stem cells (MSCs) isolated from the bone marrow of adult organisms are capable of differentiating into adipocytes, chondrocytes, myoblasts, osteoblasts, and hematopoiesis-supporting stroma. We recently demonstrated that MSCs also adopt glial cell fates when transplanted into the developing central nervous system and hence can produce tissue elements derived from a separate embryonic layer. Despite these remarkable properties, it has been difficult to establish specific criteria to characterize MSCs. Using a modified protocol for micro-serial analysis of gene expression, we cataloged 2,353 unique genes expressed by a single cell-derived colony of undifferentiated human MSCs. This analysis revealed that the MSC colony simultaneously expressed transcripts characteristic of various mesenchymal cell lineages including chondrocytes, myoblasts, osteoblasts, and hematopoiesis-supporting stroma. Therefore, the profile of expressed transcripts reflects the developmental potential of the cells. Additionally, the MSC colony expressed mRNAs characteristic of endothelial, epithelial and neuronal cell lineages, a combination that provides a unique molecular signature for the cells. Other expressed transcripts included various products involved in wound repair as well as several neurotrophic factors. A total of 268 novel transcripts were also identified, one of which is the most abundantly expressed mRNA in MSCs. This study represents the first extensive gene expression analysis of MSCs and as such reveals new insight into the biology, ontogeny, and in vivo function of the cells.