5D gravity and the discrepant G measurements

It is shown that 5D Kaluza-Klein theory stabilized by an external bulk scalar field may solve the discrepant laboratory G measurements. This is achieved by an effective coupling between gravitation and the geomagnetic field. Experimental considerations are also addressed.Comment: 13 pages, to be published in: Proceedings of the 18th Course of the School on Cosmology and Gravitation: The gravitational Constant. Generalized gravitational theories and experiments (30 April-10 May 2003, Erice). Ed. by G. T. Gillies, V. N. Melnikov and V. de Sabbata, (Kluwer), 13pp. (in print) (2003

Regulators of AWC-Mediated Olfactory Plasticity in Caenorhabditis elegans

While most sensory neurons will adapt to prolonged stimulation by down-regulating their responsiveness to the signal, it is not clear which events initiate long-lasting sensory adaptation. Likewise, we are just beginning to understand how the physiology of the adapted cell is altered. Caenorhabditis elegans is inherently attracted to specific odors that are sensed by the paired AWC olfactory sensory neurons. The attraction diminishes if the animal experiences these odors for a prolonged period of time in the absence of food. The AWC neuron responds acutely to odor-exposure by closing calcium channels. While odortaxis requires a Gα subunit protein, cGMP-gated channels, and guanylyl cyclases, adaptation to prolonged odor exposure requires nuclear entry of the cGMP-dependent protein kinase, EGL-4. We asked which candidate members of the olfactory signal transduction pathway promote nuclear entry of EGL-4 and which molecules might induce long-term adaptation downstream of EGL-4 nuclear entry. We found that initiation of long-term adaptation, as assessed by nuclear entry of EGL-4, is dependent on G-protein mediated signaling but is independent of fluxes in calcium levels. We show that long-term adaptation requires polyunsaturated fatty acids (PUFAs) that may act on the transient receptor potential (TRP) channel type V OSM-9 downstream of EGL-4 nuclear entry. We also present evidence that high diacylglycerol (DAG) levels block long-term adaptation without affecting EGL-4 nuclear entry. Our analysis provides a model for the process of long-term adaptation that occurs within the AWC neuron of C. elegans: G-protein signaling initiates long-lasting olfactory adaptation by promoting the nuclear entry of EGL-4, and once EGL-4 has entered the nucleus, processes such as PUFA activation of the TRP channel OSM-9 may dampen the output of the AWC neuron

Activation of MEK1 or MEK2 isoform is sufficient to fully transform intestinal epithelial cells and induce the formation of metastatic tumors

<p>Abstract</p> <p>Background</p> <p>The Ras-dependent ERK1/2 MAP kinase signaling pathway plays a central role in cell proliferation control and is frequently activated in human colorectal cancer. Small-molecule inhibitors of MEK1/MEK2 are therefore viewed as attractive drug candidates for the targeted therapy of this malignancy. However, the exact contribution of MEK1 and MEK2 to the pathogenesis of colorectal cancer remains to be established.</p> <p>Methods</p> <p>Wild type and constitutively active forms of MEK1 and MEK2 were ectopically expressed by retroviral gene transfer in the normal intestinal epithelial cell line IEC-6. We studied the impact of MEK1 and MEK2 activation on cellular morphology, cell proliferation, survival, migration, invasiveness, and tumorigenesis in mice. RNA interference was used to test the requirement for MEK1 and MEK2 function in maintaining the proliferation of human colorectal cancer cells.</p> <p>Results</p> <p>We found that expression of activated MEK1 or MEK2 is sufficient to morphologically transform intestinal epithelial cells, dysregulate cell proliferation and induce the formation of high-grade adenocarcinomas after orthotopic transplantation in mice. A large proportion of these intestinal tumors metastasize to the liver and lung. Mechanistically, activation of MEK1 or MEK2 up-regulates the expression of matrix metalloproteinases, promotes invasiveness and protects cells from undergoing anoikis. Importantly, we show that silencing of MEK2 expression completely suppresses the proliferation of human colon carcinoma cell lines, whereas inactivation of MEK1 has a much weaker effect.</p> <p>Conclusion</p> <p>MEK1 and MEK2 isoforms have similar transforming properties and are able to induce the formation of metastatic intestinal tumors in mice. Our results suggest that MEK2 plays a more important role than MEK1 in sustaining the proliferation of human colorectal cancer cells.</p

Outcome of crisis intervention for borderline personality disorder and post traumatic stress disorder: a model for modification of the mechanism of disorder in complex post traumatic syndromes

<p>Abstract</p> <p>Background</p> <p>This study investigates the outcome of crisis intervention for chronic post traumatic disorders with a model based on the theory that such crises manifest trauma in the present. The sufferer's behavior is in response to the current perception of dependency and entrapment in a mistrusted relationship. The mechanism of disorder is the sufferer's activity, which aims to either prove or disprove the perception of entrapment, but, instead, elicits more semblances of it in a circular manner. Patients have reasons to keep such activity private from therapy and are barely aware of it as the source of their symptoms.</p> <p>Methods</p> <p>The hypothesis is that the experimental intervention will reduce symptoms broadly within 8 to 24 h from initiation of treatment, compared to treatment as usual. The experimental intervention sidesteps other symptoms to engage patients in testing the trustworthiness of the troubled relationship with closure, thus ending the circularity of their own ways. The study compares 32 experimental subjects with 26 controls at similar crisis stabilization units.</p> <p>Results</p> <p>The results of the Brief Psychiatric Rating Scale (BPRS) supported the hypothesis (both in total score and for four of five subscales), as did results with Client Observation, a pilot instrument designed specifically for the circular behavior targeted by the experimental intervention. Results were mostly non-significant from two instruments of patient self-observation, which provided retrospective pretreatment scores.</p> <p>Conclusions</p> <p>The discussion envisions further steps to ascertain that this broad reduction of symptoms ensues from the singular correction that distinguishes the experimental intervention.</p> <p>Trial registration</p> <p>Protocol Registration System NCT00269139. The PRS URL is <url>https://register.clinicaltrials.gov</url></p

The Transcription Factor Ultraspiracle Influences Honey Bee Social Behavior and Behavior-Related Gene Expression

Behavior is among the most dynamic animal phenotypes, modulated by a variety of internal and external stimuli. Behavioral differences are associated with large-scale changes in gene expression, but little is known about how these changes are regulated. Here we show how a transcription factor (TF), ultraspiracle (usp; the insect homolog of the Retinoid X Receptor), working in complex transcriptional networks, can regulate behavioral plasticity and associated changes in gene expression. We first show that RNAi knockdown of USP in honey bee abdominal fat bodies delayed the transition from working in the hive (primarily “nursing” brood) to foraging outside. We then demonstrate through transcriptomics experiments that USP induced many maturation-related transcriptional changes in the fat bodies by mediating transcriptional responses to juvenile hormone. These maturation-related transcriptional responses to USP occurred without changes in USP's genomic binding sites, as revealed by ChIP–chip. Instead, behaviorally related gene expression is likely determined by combinatorial interactions between USP and other TFs whose cis-regulatory motifs were enriched at USP's binding sites. Many modules of JH– and maturation-related genes were co-regulated in both the fat body and brain, predicting that usp and cofactors influence shared transcriptional networks in both of these maturation-related tissues. Our findings demonstrate how “single gene effects” on behavioral plasticity can involve complex transcriptional networks, in both brain and peripheral tissues

Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference

Transcriptome 3′end organization by PCF11 links alternative polyadenylation to formation and neuronal differentiation of neuroblastoma

In gene regulation, diversification at the transcriptome 3′end is linked to differentiation and dedifferentiation. Here, the authors discover extensive transcriptome 3′end-alterations in neuroblastoma, regulated by PCF11, and provide an interactive data repository of transcriptome-wide alternative polyadenylation

MAXIMAL POWER IS UNCHANGED BY COMPETITION. IS IT A BRICK WALL OR A GLASS CEILING?

K.G. Grenier, J.M. May, E.R Eckmann, M.K. Hopkins, D.A. Oldham, K.M. Slattengren, and D.B. Thorp Gonzaga University, Spokane, WA To our knowledge, no studies have explored the effect of competition on incremental VO2max tests. Purpose: To determine whether competition leads to increased maximal exercise performance by influencing the central governor (CG). If competition is able to override the CG then it is hypothesized that performance (i.e. maximal power (Pmax)) would be improved during an incremental exercise test in a competitive setting. Methods: Sixteen college-aged males (20.7 ± 1.2 yr.) participated in a head-to-head competition (HHC). Subjects were assigned to either experimental (n=12) or confederate (n=4) groups. Baseline VO2max was determined on all subjects via an incremental exercise test on a cycle ergometer. The protocol consisted of a 5 min warm up at 50 W followed by an increasing ramp (1 W/ 2 s) until volitional exhaustion. The experimental group preformed two subsequent trials using the initial protocol in a counterbalanced order to account for a potential learning affect; one was a VO2 max retest and the other was a simulated HHC against a confederate participant. To maintain the competitive setting for the HHC, the ramp for the confederate subject stopped increasing at 70-80% of their previously determined Pmax; this ensured that the confederate always ‘won’ the HHC. In effect, the experimental subjects were competing against their own previous results. Results: Relative VO2max values were greater in the competition test than the baseline test (66.1±10.4 mL/kg/min vs. 60.6±12mL/kg/min, p\u3c.05); VO2 peak values were also greater in trial 3 than trial 1(i.e. baseline) (66.7±9.4 mL/kg/min vs. 60.6±12mL/kg/min, p\u3c.05). No differences were found in Pmax (5.0± 0.1 W/kg, mean for all trials) or in gross efficiency at max when comparing competition or test order. Maximal heart rate was greater in the competition compared to the baseline test (185±5 BPM vs. 178±7 BPM, p\u3c.05); no differences were seen in test order. Conclusion: There appears to be an order effect causing increases in relative VO2max between baseline and trial 3, but with no corresponding increase in power. Regardless of these results, competition had no effect on the ability for subjects to increase maximal power, suggesting the CG did not behave any differently during competition