Autonomous Changes Research Articles

Autonomous changes in the swimming direction of sperm in the gastropodStrombus luhuanus

The sperm of the gastropod Strombus luhuanus show dimorphism. The eusperm have a nucleus and fertilize the egg, whereas the other type of sperm, parasperm, are anucleate and are thought to assist fertilization. Here we report the autonomous changes in the swimming pattern of S. luhuanus eusperm. In artificial seawater, the eusperm collected from S. luhuanus sperm ducts formed sperm bundles and initially swam backward with asymmetric flagellar waveforms to detach from the bundles. One hour later, the sperm began to swim forward and in a circle. After an additional 1 h incubation, the sperm swam straight, with a change in the flagellar waveforms from asymmetric to symmetric. Spontaneous backward swimming with symmetric waveforms was also observed. The eusperm stored in the female seminal receptacle were motile and showed forward symmetric swimming with spontaneous backward swimming, which appeared necessary for detachment from the wall of receptacle. All of these motility changes were observed in the absence of parasperm, suggesting that these changes autonomously occur in eusperm. Our waveform analysis of these swimming patterns revealed that only the swimming with symmetric waveform showed reverse propagation of the flagellar waveforms. Both types of backward swimming were diminished in Ca(2+)-free seawater and in seawater containing Ni(2+), indicating the regulation of swimming direction by Ca(2+)-dependent signal transduction.

Stem cell aging and the implications for stem cell-based therapies for aging-related diseases and aged tissues

Adult stem cells exist in most mammalian tissues to maintain their homeostasis and help repair them. Reductions in adult stem cell function and/or number are clearly associated with aging, however, the causal correlations between such findings and the effects of aging are largely unknown. Some stem cell functional changes, such as the loss of lineage specificity and self-renewal capacity, senescence and transformation, arise in stem cells autonomously during the aging process. These autonomous changes of stem cell functions reflect the damaging effects of age on the genome, epigenome, and proteome. Other stem cell functional changes are influenced by the age-related changes in the local microenvironments (niches) or systemic environments. If stem cell-based therapy can be used not only for age-related degenerative diseases, but also normal functional declines associated with aging, consideration of the behavior of stem cells based on effects from the local microenvironments (niches) and systemic environments in older individuals will therefore be needed.

Medicine Worse than the Malady: Cure Rates, Population Shifts, and Health Insurance

We examine the welfare effects of the interaction of three types of technological progress in medicine and health insurance; some paradoxes emerge. The model specifies three types of people: W (well); H (sick with high cure rate if treated); and L (sick with low cure rate if treated). There are four insurance modes: Indemnity (I): fully covered treatments for Hs, cash bribes for Ls to forgo treatment); Deductible (D): partially covered treatments for Hs, no treatments for Ls); Zero (Z): no insurance and no treatments); and Full (F): fully covered treatments for Hs and Ls). The three types of technological progress are represented as population shifts from sicker to healthier classes of people; for brevity, we call the shifts L—>W, H—>W, and L—>H, and describe each as follows:L—>W: Improved ability to prevent illness among Ls- unambiguously improves welfare and seems to yield intuitive mode sequences.H—>W: Improved ability to prevent illness among Hs- unambiguously improves welfare but sometimes yields surprising mode sequences. Examples: F-Z (full insurance when there are many Hs, no insurance when there are fewer Hs); and D-F-D (Hs partially covered, then fully covered, then only partially covered once again. Ls not treated, then treated, then not treated once again.).L—>H: Some would-be Ls become more highly treatable Hs. Here, technological progress not only yields surprising mode shifts (e.g., D-Z-I-Z), but the welfare effects of progress are ambiguous. This is because L—>H may lead to more people being treated and cured (a welfare gain), but at a cost of higher premiums for all subscribers (a welfare loss).The paradoxical results are in part explained by the fact that utility is a concave function of wealth and a linear function of health.The three shifts could also be interpreted as autonomous demographic changes rather than as technological progress.

Dynamic dune management, integrating objectives of nature development and coastal safety: Examples from the Netherlands

This paper discusses and compares results of management interventions to remobilise dunes and obtain more autonomous changes in foredunes resulting from a change in coastal defence policy. In recent decades, nature conservation managers tried to restore aeolian dynamics and dune mobility landward of foredunes to maintain threatened, rare pioneer species. Results indicate that destabilisation activities yielded an important increase of blowing sand and its effects on ecology but with a limited effect on the desired integral remobilization of dunes. Roots remaining in the sand after removal of vegetation and soil is one of the main problems. Follow up removal of roots for 3 to 5years seems to be essential, but it is not clear whether the dunes will remain mobile in the long term.In 1990 the Dutch government decided to maintain the position of the coastline by artificial sand nourishment. An intensive management of the foredunes was no longer required. Consequently, natural processes in the foredunes revived, and the sediment budget of the beach–dune system changed. Two main types of responses are visible. In some areas, increased input of sand resulted in the development of embryonic dunes seaward of the former foredunes, leading to increased stabilisation of the former foredunes. In other areas, development of embryonic dunes was insignificant despite the increased sand input, but wind erosion features developed in the foredunes, and the environment was more dynamic. The reasons for the differences are not clear, and the interaction between shoreface, beach and dunes is still poorly understood.Until now, attempts to mobilise the inner dunes were independent of changes made to the foredunes. We argue that an integrated, dynamic approach to coastal management, taking account of all relevant functions (including safety and natural values) and the dune–beach system as a whole, may provide new and durable solutions. An integrated approach would ideally provide fresh sand to the system by sand nourishment; define a wide safety zone, which enables the transition zone of beach to foredunes to develop freely; reserve space for natural processes without restrictions; and stimulate natural redistribution of sand within the system and restore inland transport of sand by removing vegetation behind the foredunes. A long time scale (several decades) is needed for this approach to be successful.

Pathogenesis of Age-Related Bone Loss in Humans

Although data from rodent systems are extremely useful in providing insights into possible mechanisms of age-related bone loss, concepts evolving from animal models need to ultimately be tested in humans. This review provides an update on mechanisms of age-related bone loss in humans based on the author's knowledge of the field and focused literature reviews. Novel imaging, experimental models, biomarkers, and analytic techniques applied directly to human studies are providing new insights into the patterns of bone mass acquisition and loss as well as the role of sex steroids, in particular estrogen, on bone metabolism and bone loss with aging in women and men. These studies have identified the onset of trabecular bone loss at multiple sites that begins in young adulthood and remains unexplained, at least based on current paradigms of the mechanisms of bone loss. In addition, estrogen appears to be a major regulator of bone metabolism not only in women but also in men. Studies assessing mechanisms of estrogen action on bone in humans have identified effects of estrogen on RANKL expression by several different cell types in the bone microenvironment, a role for TNF-α and IL-1β in mediating effects of estrogen deficiency on bone, and possible regulation of the Wnt inhibitor, sclerostin, by estrogen. There have been considerable advances in our understanding of age-related bone loss in humans. However, there are also significant gaps in knowledge, particularly in defining cell autonomous changes in bone in human studies to test or validate concepts emerging from studies in rodents. Decision Editor: Luigi Ferrucci, MD, PhD.

Myocardial Notch Signaling Reprograms Cardiomyocytes to a Conduction-Like Phenotype

Notch signaling has previously been shown to play an essential role in regulating cell fate decisions and differentiation during cardiogenesis in many systems including Drosophila, Xenopus, and mammals. We hypothesized that Notch may also be involved in directing the progressive lineage restriction of cardiomyocytes into specialized conduction cells. In hearts where Notch signaling is activated within the myocardium from early development onward, Notch promotes a conduction-like phenotype based on ectopic expression of conduction system-specific genes and cell autonomous changes in electrophysiology. With the use of an in vitro assay to activate Notch in newborn cardiomyocytes, we observed global changes in the transcriptome, and in action potential characteristics, consistent with reprogramming to a conduction-like phenotype. Notch can instruct the differentiation of chamber cardiac progenitors into specialized conduction-like cells. Plasticity remains in late-stage cardiomyocytes, which has potential implications for engineering of specialized cardiovascular tissues.

Myocardial Notch Signaling Reprograms Cardiomyoctes to a Conduction‐Like Phenotype

Notch signaling has previously been shown to play an essential role in regulating cell fate decisions in many systems. We hypothesized that Notch may be involved in directing the progressive lineage restriction of cardiomyocytes into specialized conduction cells. In murine hearts where Notch signaling is activated within the myocardium from early development onwards, Notch promotes a conduction‐like phenotype as evidenced by ectopic expression of conduction system‐specific genes, as well as cell autonomous changes in cellular electrophysiology. Activation of Notch in newborn ventricular cardiomyocytes from Contactin2‐EGFP transgenic mice, which specifically labels conduction cells, demonstrates Notch‐induced changes in “chamber” ventricular cardiomyocytes consistent with a phenotypic switch to Purkinje‐like cells, including transcriptional changes, action potential prolongation and hyperpolarization of the resting membrane potential. Taken together, this suggests that Notch can instruct the differentiation of cardiac progenitors into specialized conduction‐like cells and that this plasticity remains in late‐stage cardiomyocytes, which has potential implications for engineering of specialized cardiovascular tissues.Grant Funding Source: Career Award for Medical Scientists Burroughs Wellcome Fund and K08 HL107449‐01 to SR, U01 HL100405‐1 to JAE

KSHV Induction of Angiogenic and Lymphangiogenic Phenotypes

Kaposi’s sarcoma (KS) is a highly vascularized tumor supporting large amounts of neo-angiogenesis. The major cell type in KS tumors is the spindle cell, a cell that expresses markers of lymphatic endothelium. KSHV, the etiologic agent of KS, is found in the spindle cells of all KS tumors. Considering the extreme extent of angiogenesis in KS tumors at all stages it has been proposed that KSHV directly induces angiogenesis in a paracrine fashion. In accordance with this theory, KSHV infection of endothelial cells in culture induces a number of host pathways involved in activation of angiogenesis and a number of KSHV genes themselves can induce pathways involved in angiogenesis. Spindle cells are phenotypically endothelial in nature, and therefore, activation through the induction of angiogenic and/or lymphangiogenic phenotypes by the virus may also be directly involved in spindle cell growth and tumor induction. Accordingly, KSHV infection of endothelial cells induces cell autonomous angiogenic phenotypes to activate host cells. KSHV infection can also reprogram blood endothelial cells to lymphatic endothelium. However, KSHV induces some blood endothelial specific genes upon infection of lymphatic endothelial cells creating a phenotypic intermediate between blood and lymphatic endothelium. Induction of pathways involved in angiogenesis and lymphangiogenesis are likely to be critical for tumor cell growth and spread. Thus, induction of both cell autonomous and non-autonomous changes in angiogenic and lymphangiogenic pathways by KSHV likely plays a key role in the formation of KS tumors.

Basal Forebrain Thermoregulatory Mechanism Modulates Auto-Regulated Sleep

Regulation of body temperature and sleep are two physiological mechanisms that are vital for our survival. Interestingly neural structures implicated in both these functions are common. These areas include the medial preoptic area (POA), the lateral POA, the ventrolateral POA, the median preoptic nucleus, and the medial septum, which form part of the basal forebrain (BF). When given a choice, rats prefer to stay at an ambient temperature of 27°C, though the maximum sleep was observed when they were placed at 30°C. Ambient temperature around 27°C should be considered as the thermoneutral temperature for rats in all sleep studies. At this temperature the diurnal oscillations of sleep and body temperature are properly expressed. The warm sensitive neurons of the POA mediate the increase in sleep at 30°C. Promotion of sleep during the rise in ambient temperature from 27 to 30°C, serve a thermoregulatory function. Autonomous thermoregulatory changes in core body temperature and skin temperature could act as an input signal to modulate neuronal activity in sleep-promoting brain areas. The studies presented here show that the neurons of the BF play a key role in regulating sleep. BF thermoregulatory system is a part of the global homeostatic sleep regulatory mechanism, which is auto-regulated.

Complex Shapes and Dynamics of Dissolving Drops of Dichloromethane

There is a growing interest in synthetic, chemical systems capable of undergoing autonomous shape changes and/or self-motion. Important examples include solid objects such as catalytic Au/Pt nanorods, mechanically responsive gels driven by oscillating reactions, and liquid systems in which self-motion is induced by surface-tension gradients. The latter class of systems includes iodine/iodide-containing oil droplets on glass surfaces under aqueous solutions of stearyltrimethylammonium chloride as well as drop motion on an alkylsilane-treated silicon surface with spatial “wettability” changes. Droplet motion on air–water interfaces is usually driven by aMarangoni effect involving temperature or concentration gradients. A typical example are pentanol droplets on water, which depending on the drop volume, perform erratic or unidirectional motion and also show very disorganized forms of droplet fission. This fission can extend from the millimeter-scale down to nanoscopic micelles. Herein, we investigate the dynamics of water-saturated dichloromethane (CH2Cl2, 25 mL) droplets on aqueous solutions of cetyltrimethylammonium bromide (CTAB). Figure 1 is a qualitative phase diagram describing the macroscopic dynamics in the CH2Cl2/CTAB system in terms of the elapsed reaction time and the surfactant concentration. The data are representative for the fourth and fifth drops added. The diagram shows a variety of complex drop shapes and dynamics that we identified to be the most characteristic ones. For each concentration we have studied the dynamics of five successive drops. In general these dichloromethane-accumulating experiments reveal no marked differences; however, the fourth and fifth drops deviate from their predecessors during the late stages of dissolution. These altered dynamics typically match the behavior of drops at a slightly higher CTAB concentration. The life time of the dichloromethane drops varies systematically between approximately 20 and 90 s. This large range is mainly caused by changes in the initial induction period during which drops are stationary and have a circular rim. Complex phenomena are found only for surfactant concentrations above a critical value [CTAB]crit 0.25 mmolL . In the absence of surfactant or below [CTAB]crit, the drops spread out over a large area and solubilize rapidly (< 15 s) without noteworthy macroscopic features. For surfactant concentration close to [CTAB]crit (left column in Figure 1), the initial dichloromethane drops are relatively flat. We also observe that the water surface around the drop supports a disk-shaped film. The macroscopic dynamics involve several successive stages: During the first stage, the edge of the film breaks into small droplets that are continuously ejected and quickly disappear. Then the drop abruptly moves away from the center of the film to maneuver back and forth along a nearly stationary line. During these lateral oscillations, each directional change causes the expulsion of a line of small droplets. After a while, the drop starts to move steadily along a circular orbit larger than its own diameter. Finally all motion ceases, the drop becomes circular again, shrinks and vanishes. At a surfactant concentration of 0.5 mmolL 1 (second column in Figure 1), the dichloromethane drops undergo a similar sequence of motion patterns. However, the dynamics Figure 1. Qualitative description of the drop evolution in the CH2Cl2/ CTAB system at five different concentrations of the surfactant CTAB. The typical life time of the dissolving droplets ranges between 20 and 90 s. The time axis is not to scale as the diagram emphasizes distinct, successive states in the drop evolution. Single arrows indicate rotation of the drop around its geometrical center. The double arrow indicates that the drop moves back and forth along a fixed line. The field of view of all frames corresponds to 13 13 mm.

Disruption of bone morphogenetic protein receptor 2 (BMPR2) in mammary tumors promotes metastases through cell autonomous and paracrine mediators

Bone morphogenetic proteins (BMPs) are members of the TGF-β superfamily of signaling molecules. BMPs can elicit a wide range of effects in many cell types and have previously been shown to induce growth inhibition in carcinoma cells as well as normal epithelia. Recently, it has been demonstrated that BMP4 and BMP7 are overexpressed in human breast cancers and may have tumor suppressive and promoting effects. We sought to determine whether disruption of the BMP receptor 2 (BMPR2) would alter mammary tumor progression in mice that express the Polyoma middle T antigen. Mice expressing Polyoma middle T antigen under the mouse mammary tumor virus promoter were combined with mice that have doxycycline-inducible expression of a dominant-negative (DN) BMPR2. We did not observe any differences in tumor latency. However, mice expressing the BMPR2-DN had a fivefold increase in lung metastases. We characterized several cell autonomous changes and found that BMPR2-DN-expressing tumor cells had higher rates of proliferation. We also identified unique changes in inflammatory cells and secreted chemokines/cytokines that accompanied BMPR2-DN-expressing tumors. By immunohistochemistry, it was found that BMPR2-DN primary tumors and metastases had an altered reactive stroma, indicating specific changes in the tumor microenvironment. Among the changes we discovered were increased myeloid derived suppressor cells and the chemokine CCL9. BMP was shown to directly regulate CCL9 expression. We conclude that BMPR2 has tumor-suppressive function in mammary epithelia and microenvironment and that disruption can accelerate mammary carcinoma metastases.

Abstract 922: Disruption of bone morphogenetic protein receptor 2 accelerates mammary carcinoma metastasis to the lung

Abstract Bone Morphogenetic Proteins (BMPs) are members of the Transforming Growth Factor β (TGFβ) superfamily of signaling molecules. BMPs can elicit a wide range of effects in many cell types and have previously been shown to induce growth inhibition in cancers as well as normal epithelia. Recently, it has been demonstrated that BMP4 and BMP7 are overexpressed in human breast cancers and may have both tumor suppressive and promoting effects. We sought to determine whether disruption of the Bone Morphogenetic Protein Receptor 2 (BMPR2) would alter mammary tumor progression in mice that express the Polyoma middle T antigen (PyVmT). Mice expressing PyVmT under the mammary specific MMTV promoter were combined with mice that have Doxycycline inducible expression of a dominant negative (DN) BMPR2. We did not observe any differences in tumor latency. However, when we measured pulmonary metastases, we found that mice expressing the BMPR2-DN had a five fold increase in lung metastases. We characterized several cell autonomous changes and found that BMPR2-DN expressing tumor cells had higher rates of proliferation and epithelial to mesenchymal transition (EMT). We also identified unique changes in the tumor microenvironment, which included inflammatory cells and secreted chemokines/ cytokines that accompanied BMPR2-DN expressing tumors. We identified several molecules including ccl-9 (MIP1γ), which was elevated in BMPR2-DN expressing tumors. Ccl-9 has recently been shown to be an important chemokine in the recruitment of myeloid cells that promote metastatic progression. We discovered that tumor cells treated exogenously with BMP4 ligand repressed ccl-9 mRNA and that this repression was limited in cells expressing BMPR2-DN. We conclude that BMPR2 has tumor suppressive function in mammary epithelia and that disruption can accelerate mammary carcinoma metastases via paracrine stimulation of myeloid cells in the tumor microenvironment. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 922. doi:10.1158/1538-7445.AM2011-922

Energy Conservation More Effective With Rebound Policy

This article sketches the problem of indirect energy use effects, also known as rebound, of energy conservation. There is widespread support for energy conservation, especially when it is voluntary, as this seems a cheap way to realize environmental and energy-climate goals. However, this overlooks the phenomenon of rebound. The topic of energy rebound has mainly attracted attention from energy analysts, but has been surprisingly neglected in environmental economics, even though economists generally are concerned with indirect or economy-wide impacts of technical change and policies. This paper presents definitions and interpretations of energy and environmental rebound, as well as four fundamental reasons for the existence of the rebound phenomenon. It further offers the most complete list of rebound pathways or mechanisms available in the literature. In addition, it discusses empirical estimates of rebound and addresses the implications of uncertainties and difficulties in assessing rebound. Suggestions are offered for strategies and public policies to contain rebound. It is advised that rebound evaluation is an essential part of environmental policy and project assessments. As opposed to earlier studies, this paper stresses the relevance of the distinction between energy conservation resulting from autonomous demand changes and from efficiency improvements in technology/equipment. In addition, it argues that rebound is especially relevant for developing countries.

Capital accumulation, labour market institutions and unemployment in the medium run

According to the mainstream view, labour market institutions (LMIs) are the key determinants of unemployment in the medium run. The actual empirical explanatory power of measures for labour market institutions, however, has recently been called into question. The Keynesian view holds periods of high real interest rates and insufficient capital accumulation responsible for unemployment. Empirical work in this tradition has paid little attention to the role of LMIs. This paper contributes to the debate by highlighting the role of autonomous changes in capital accumulation as a macroeconomic shock. In the empirical analysis, medium-term unemployment is explained by capital accumulation, LMIs and a number of macroeconomic shocks in a panel analysis covering 20 OECD countries. The economic effects of changes in LMI, variations in capital accumulation and other macro shocks are compared. Capital accumulation and the real interest rate are found to have statistically significant effects that are robust to the inclusion of control variables and show larger effects than LMI.

Abstract PR2: Therapeutic intervention targeting a Hedgehog-dependent barrier to drug delivery in pancreatic cancer

Abstract Ductal pancreatic tumors are unusually resistant to chemotherapy, exhibiting primary resistance to each of the numerous regimens tested to date. These tumors are also unusually desmoplastic and harbor a sparse and inefficient vasculature. The resulting lack of perfusion appears to play a role in the inefficient delivery of numerous chemotherapeutic agents to the parenchyma of pancreatic tumors. Recent evidence has implicated the sonic hedgehog pathway in promoting desmoplasia through a paracrine signaling mechanism active in pancreatic tumors of both humans and the Kras/p53/PdxCre (KPC) mouse model. We sought to evaluate the dependence of stromal desmoplasia on Hedgehog (Hh) pathway signaling and, by extension, assess the effects of Hh pathway inhibition on drug delivery and chemoresistance. Using IPI-926, a semisynthetic inhibitor of the Smoothened protein, we found that stromal contribution was markedly diminished within 10 days of inhibition of the Hh pathway. Paradoxically, the depletion of stromal cells was coincident with an increase in microvessel density, despite previous data indicating a pro-angiogenic role for the Hh pathway. These non-cell autonomous changes resulted in an increase in the delivery of small molecules to KPC pancreatic tumors and an increase in apoptosis when administered in combination with gemcitabine. Ultimately, mice treated with both IPI-926 and gemcitabine had a significant extension of survival and a decrease in the incidence of liver metastases. We conclude that the Hh pathway plays an important role in the maintenance of pancreatic tumor stroma and that this contributes to the primary chemoresistance of pancreatic tumors. These data also support the clinical evaluation of agents that target the stroma in pancreatic cancer. Citation Information: Clin Cancer Res 2010;16(14 Suppl):PR2.

Dietary fat alters pulmonary metastasis of mammary cancers through cancer autonomous and non-autonomous changes in gene expression

Metastasis virulence, a significant contributor to breast cancer prognosis, is influenced by environmental factors like diet. We previously demonstrated in an F2 mouse population generated from a cross between the M16i polygenic obese and MMTV-PyMT mammary cancer models that high fat diet (HFD) decreases mammary cancer latency and increases pulmonary metastases compared to a matched control diet (MCD). Genetic analysis detected eight modifier loci for pulmonary metastasis, and diet significantly interacted with all eight loci. Here, gene expression microarray analysis was performed on mammary cancers from these mice. Despite the substantial dietary impact on metastasis and its interaction with metastasis modifiers, HFD significantly altered the expression of only five genes in mammary tumors; four of which, including serum amyloid A (Saa), are downstream of the tumor suppressor PTEN. Conversely, HFD altered the expression of 211 hepatic genes in a set of tumor free F2 control mice. Independent of diet, pulmonary metastasis virulence correlates with mammary tumor expression of genes involved in endocrine cancers, inflammation, angiogenesis, and invasion. The most significant virulence-associated network harbored genes also found in human adipose or mammary tissue, and contained upregulated Vegfa as a central node. Additionally, expression of Btn1a1, a gene physically located near a putative cis-acting eQTL on chromosome 13 and one of the metastasis modifiers, correlates with metastasis virulence. These data support the existence of diet-dependent and independent cancer modifier networks underlying differential susceptibility to mammary cancer metastasis and suggest that diet influences cancer metastasis virulence through tumor autonomous and non-autonomous mechanisms.

Cardiac Autonomic Regulation under Hypnosis Assessed by Heart Rate Variability: Spectral Analysis and Fractal Complexity

Objective: This study examined the effects of hypnosis on autonomic cardiac control. We hypothesized a modification of autonomic modulation of the heart rate with an enhanced vagal tone during hypnosis compared to baseline. Methods: In 12 healthy subjects (6 men and 6 women, 22.2 ± 1.0 years of age) ECG was recorded at baseline and during hypnosis. Heart rate variability parameters were obtained in the frequency domain (LFnu: low frequency normalized units, and HFnu: high frequency normalized units) and from nonlinear analysis methods (detrended fluctuation analysis, DFA). Results: Compared to the control condition, hypnosis showed a significantly decreased LFnu, a significantly increased HFnu, and a significantly decreased LF/HF. DFA showed a significantly decreased short-range similarity. Heart rate remained unchanged. Conclusion: Autonomic cardiac tone is significantly modified during hypnosis by shifting the balance of the sympathovagal interaction toward an enhanced parasympathetic modulation, accompanied by a reduction of the sympathetic tone and a decreased short-range similarity but without a concomitant change in heart rate. Central and secondary autonomous nervous system changes induced by hypnosis are a possible explanation for our results. Another highly probable explanation is given by a variation in the depth of respiration. Hypnosis appears to prevent the autonomic responses expected during neutral stimulation.

Capital Accumulation, Labour Market Institutions, and Unemployment in the Medium Run

According to the mainstream view, labour market institutions (LMI) are the key determinants of unemployment in the medium run. The actual empirical explanatory power of measures for labour market institutions, however, has been called into question recently (Baker et al 2005, Baccaro and Rei 2007). The Keynesian view holds periods of high real interest rates and insufficient capital accumulation responsible for unemployment (Arestis et al 2007). Empirical work in this tradition has paid little attention to role of LMI. This paper contributes to the debate by highlighting the role of autonomous changes in capital accumulation as a macroeconomic shock. In the empirical analysis, medium-term unemployment is explained by capital accumulation, labour market institutions and a number of macroeconomic shocks in a panel analysis covering 20 OECD countries. The economic effects of institutional changes, variations in capital accumulation and other macro shocks are compared. Capital accumulation and the real interest rate are found to have statistically significant effects that are robust to the inclusion of control variables and show larger effects than LMI.

Changes in haemodynamic and autonomous nervous system parameters measured non-invasively throughout normal pregnancy

Objective To examine non-invasively haemodynamic and autonomous parameters throughout normal pregnancy. Study design We used the Task Force ® Monitor 3040i system to retrieve, record, and calculate haemodynamic as well as autonomous parameters. 20 healthy women were included and scheduled for longitudinal examinations throughout normal pregnancy. Heart rate (HR), blood pressure (BP), stroke volume (SV), cardiac output (CO), systemic vascular resistance (SVR), heart rate variability (HRV), blood pressure variability (BPV), and baroreceptor sensitivity (BRS) were measured. Measurements were performed at gestational week 10 +0–13 +6, 15 +0–18 +6, 20 +0–22 +6, and >30 +0. Results HR increased during gestation showing a significant increase at III versus I trimester (74 bpm vs. 88 bpm, P < .05). Mean arterial pressure remained stable until III trimester, when a significant increase compared to I trimester could be noted (78 mm Hg vs. 86 mm Hg, P < .05). SV and CO remained relatively stable in I and II trimester, and in III trimester significant decreases were observed. In contrast, SVR increased significantly at III trimester ( P < .001). Whereas HRV and BPV did not change at different gestational ages, BRS was significantly lower in III trimester compared to I trimester values ( P < .05). Conclusion The non-invasive determination of cardiovascular and autonomous parameters throughout pregnancy is possible and the results of this pilot study can serve as basic parameters for classifying and assessing cardiovascular and autonomous changes in pathological conditions in pregnancy such as hypertensive disorders.

Senescent Stromal-Derived Osteopontin Promotes Preneoplastic Cell Growth

Alterations in the tissue microenvironment collaborate with cell autonomous genetic changes to contribute to neoplastic progression. The importance of the microenvironment in neoplastic progression is underscored by studies showing that fibroblasts isolated from a tumor stimulate the growth of preneoplastic and neoplastic cells in xenograft models. Similarly, senescent fibroblasts promote preneoplastic cell growth in vitro and in vivo. Because senescent cells accumulate with age, their presence is hypothesized to facilitate preneoplastic cell growth and tumor formation in older individuals. To identify senescent stromal factors directly responsible for stimulating preneoplastic cell growth, we carried out whole-genome transcriptional profiling and compared senescent fibroblasts with their younger counterparts. We identified osteopontin (OPN) as one of the most highly elevated transcripts in senescent fibroblasts. Importantly, reduction of OPN protein levels by RNA interference did not affect senescence induction in fibroblasts; however, it dramatically reduced the growth-promoting activities of senescent fibroblasts in vitro and in vivo, showing that OPN is necessary for paracrine stimulation of preneoplastic cell growth. In addition, we found that recombinant OPN was sufficient to stimulate preneoplastic cell growth. Finally, we show that OPN is expressed in senescent stroma within preneoplastic lesions that arise following 7,12-dimethylbenz(a)anthracene/12-O-tetradecanoylphorbol-13-acetate treatment of mice, suggesting that stromal-derived OPN-mediated signaling events affect neoplastic progression.