When planning results in loss of control: intention-based reflexivity and working-memory

In this review, the authors discuss the seemingly paradoxical loss of control associated with states of high readiness to execute a plan, termed “intention-based reflexivity.” The review suggests that the neuro-cognitive systems involved in the preparation of novel plans are different than those involved in preparation of practiced plans (i.e., those that have been executed beforehand). When the plans are practiced, intention-based reflexivity depends on the prior availability of response codes in long-term memory (LTM). When the plans are novel, reflexivity is observed when the plan is pending and the goal has not yet been achieved. Intention-based reflexivity also depends on the availability of working-memory (WM) limited resources and the motivation to prepare. Reflexivity is probably related to the fact that, unlike reactive control (once a plan is prepared), proactive control tends to be relatively rigid

Effect of diindolylmethane supplementation on low-grade cervical cytological abnormalities: double-blind, randomised, controlled trial

This work was supported by a Cancer Research UK project grant (C8162/A4609 project costs) and a programme grant (C8162/A10406)

The Large Array Survey Telescope -- System Overview and Performances

The Large Array Survey Telescope (LAST) is a wide-field visible-light telescope array designed to explore the variable and transient sky with a high cadence. LAST will be composed of 48, 28-cm f/2.2 telescopes (32 already installed) equipped with full-frame backside-illuminated cooled CMOS detectors. Each telescope provides a field of view (FoV) of 7.4 deg^2 with 1.25 arcsec/pix, while the system FoV is 355 deg^2 in 2.9 Gpix. The total collecting area of LAST, with 48 telescopes, is equivalent to a 1.9-m telescope. The cost-effectiveness of the system (i.e., probed volume of space per unit time per unit cost) is about an order of magnitude higher than most existing and under-construction sky surveys. The telescopes are mounted on 12 separate mounts, each carrying four telescopes. This provides significant flexibility in operating the system. The first LAST system is under construction in the Israeli Negev Desert, with 32 telescopes already deployed. We present the system overview and performances based on the system commissioning data. The Bp 5-sigma limiting magnitude of a single 28-cm telescope is about 19.6 (21.0), in 20 s (20x20 s). Astrometric two-axes precision (rms) at the bright-end is about 60 (30)\,mas in 20\,s (20x20 s), while absolute photometric calibration, relative to GAIA, provides ~10 millimag accuracy. Relative photometric precision, in a single 20 s (320 s) image, at the bright-end measured over a time scale of about 60 min is about 3 (1) millimag. We discuss the system science goals, data pipelines, and the observatory control system in companion publications.Comment: Submitted to PASP, 15p

B-type natriuretic peptide-induced delayed modulation of TRPV1 and P2X3 receptors of mouse trigeminal sensory neurons

Important pain transducers of noxious stimuli are small- and medium-diameter sensory neurons that express transient receptor vanilloid-1 (TRPV1) channels and/or adenosine triphosphate (ATP)-gated P2X3 receptors whose activity is upregulated by endogenous neuropeptides in acute and chronic pain models. Little is known about the role of endogenous modulators in restraining the expression and function of TRPV1 and P2X3 receptors. In dorsal root ganglia, evidence supports the involvement of the natriuretic peptide system in the modulation of nociceptive transmission especially via the B-type natriuretic peptide (BNP) that activates the natriuretic peptide receptor-A (NPR-A) to downregulate sensory neuron excitability. Since the role of BNP in trigeminal ganglia (TG) is unclear, we investigated the expression of BNP in mouse TG in situ or in primary cultures and its effect on P2X3 and TRPV1 receptors of patch-clamped cultured neurons. Against scant expression of BNP, almost all neurons expressed NPRA at membrane level. While BNP rapidly increased cGMP production and Akt kinase phosphorylation, there was no early change in passive neuronal properties or responses to capsaicin, \u3b1,\u3b2-meATP or GABA. Nonetheless, 24 h application of BNP depressed TRPV1 mediated currents (an effect blocked by the NPR-A antagonist anantin) without changing responses to \u3b1,\u3b2-meATP or GABA. Anantin alone decreased basal cGMP production and enhanced control \u3b1,\u3b2-meATP-evoked responses, implying constitutive regulation of P2X3 receptors by ambient BNP. These data suggest a slow modulatory action by BNP on TRPV1 and P2X3 receptors outlining the role of this peptide as a negative regulator of trigeminal sensory neuron excitability to nociceptive stimuli. \ua9 2013 Vilotti et al

Induction of G1 and G2/M cell cycle arrests by the dietary compound 3,3'-diindolylmethane in HT-29 human colon cancer cells

<p>Abstract</p> <p>Background</p> <p>3,3'-Diindolylmethane (DIM), an indole derivative produced in the stomach after the consumption of broccoli and other cruciferous vegetables, has been demonstrated to exert anti-cancer effects in both <it>in vivo </it>and <it>in vitro </it>models. We have previously determined that DIM (0 – 30 μmol/L) inhibited the growth of HT-29 human colon cancer cells in a concentration-dependent fashion. In this study, we evaluated the effects of DIM on cell cycle progression in HT-29 cells.</p> <p>Methods</p> <p>HT-29 cells were cultured with various concentrations of DIM (0 – 30 μmol/L) and the DNA was stained with propidium iodide, followed by flow cytometric analysis. [³H]Thymidine incorporation assays, Western blot analyses, immunoprecipitation and <it>in vitro </it>kinase assays for cyclin-dependent kinase (CDK) and cell division cycle (CDC)2 were conducted.</p> <p>Results</p> <p>The percentages of cells in the G1 and G2/M phases were dose-dependently increased and the percentages of cells in S phase were reduced within 12 h in DIM-treated cells. DIM also reduced DNA synthesis in a dose-dependent fashion. DIM markedly reduced CDK2 activity and the levels of phosphorylated retinoblastoma proteins (Rb) and E2F-1, and also increased the levels of hypophosphorylated Rb. DIM reduced the protein levels of cyclin A, D1, and CDK4. DIM also increased the protein levels of CDK inhibitors, p21^CIP1/WAF1and p27^KIPI. In addition, DIM reduced the activity of CDC2 and the levels of CDC25C phosphatase and cyclin B1.</p> <p>Conclusion</p> <p>Here, we have demonstrated that DIM induces G1 and G2/M phase cell cycle arrest in HT-29 cells, and this effect may be mediated by reduced CDK activity.</p

Non-Standard Neutrino Interactions at One Loop

Neutrino oscillation experiments are known to be sensitive to Non-Standard Interactions (NSIs). We extend the NSI formalism to include one-loop effects. We discuss universal effects induced by corrections to the tree level W exchange, as well as non-universal effects that can arise from scalar charged current interactions. We show how the parameters that can be extracted from the experiments are obtained from various loop amplitudes, which include vertex corrections, wave function renormalizations, mass corrections as well as box diagrams. As an illustrative example, we discuss NSIs at one loop in the Minimal Supersymmetric Standard Model (MSSM) with generic lepton flavor violating sources in the soft sector. We argue that the size of one-loop NSIs can be large enough to be probed in future neutrino oscillation experiments.Comment: 27 pages, 4 figure

3, 3′-Diindolylmethane Exhibits Antileukemic Activity In Vitro and In Vivo through a Akt-Dependent Process

3,3′-diindolylmethane (DIM), one of the active products derived from Brassica plants, is a promising antitumor agent. The present study indicated that DIM significantly induced apoptosis in U937 human leukemia cells in dose- and time-dependent manners. These events were also noted in other human leukemia cells (Jurkat and HL-60) and primary human leukemia cells (AML) but not in normal bone marrow mononuclear cells. We also found that DIM-induced lethality is associated with caspases activation, myeloid cell leukemia-1 (Mcl-1) down-regulation, p21cip1/waf1 up-regulation, and Akt inactivation accompanied by c-jun NH2-terminal kinase (JNK) activation. Enforced activation of Akt by a constitutively active Akt construct prevented DIM-mediated caspase activation, Mcl-1 down-regulation, JNK activation, and apoptosis. Conversely, DIM lethality was potentiated by the PI3K inhibitor LY294002. Interruption of the JNK pathway by pharmacologic or genetic approaches attenuated DIM-induced caspases activation, Mcl-1 down-regulation, and apoptosis. Lastly, DIM inhibits tumor growth of mouse U937 xenograft, which was related to induction of apoptosis and inactivation of Akt, as well as activation of JNK. Collectively, these findings suggest that DIM induces apoptosis in human leukemia cell lines and primary human leukemia cells, and exhibits antileukemic activity in vivo through Akt inactivation and JNK activation

Clinical Trials in Head Injury

Traumatic brain injury (TBI) remains a major public health problem globally. In the United States the incidence of closed head injuries admitted to hospitals is conservatively estimated to be 200 per 100,000 population, and the incidence of penetrating head injury is estimated to be 12 per 100,000, the highest of any developed country in the world. This yields an approximate number of 500,000 new cases each year, a sizeable proportion of which demonstrate signficant long-term disabilities. Unfortunately, there is a paucity of proven therapies for this disease. For a variety of reasons, clinical trials for this condition have been difficult to design and perform. Despite promising pre-clinical data, most of the trials that have been performed in recent years have failed to demonstrate any significant improvement in outcomes. The reasons for these failures have not always been apparent and any insights gained were not always shared. It was therefore feared that we were running the risk of repeating our mistakes. Recognizing the importance of TBI, the National Institute of Neurological Disorders and Stroke (NINDS) sponsored a workshop that brought together experts from clinical, research, and pharmaceutical backgrounds. This workshop proved to be very informative and yielded many insights into previous and future TBI trials. This paper is an attempt to summarize the key points made at the workshop. It is hoped that these lessons will enhance the planning and design of future efforts in this important field of research.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63185/1/089771502753754037.pd