Functional imaging of neural responses to expectancy and experience of monetary gains and losses

Neural responses accompanying anticipation and experience of monetary gains and losses were monitored by functional magnetic resonance imaging. Trials comprised an initial "prospect" (expectancy) phase, when a set of three monetary amounts was displayed, and a subsequent "outcome" phase, when one of these amounts was awarded. Hemodynamic responses in the sublenticular extended amygdala (SLEA) and orbital gyrus tracked the expected values of the prospects, and responses to the highest value set of outcomes increased monotonically with monetary value in the nucleus accumbens, SLEA, and hypothalamus. Responses to prospects and outcomes were generally, but not always, seen in the same regions. The overlap of the observed activations with those seen previously in response to tactile stimuli, gustatory stimuli, and euphoria-inducing drugs is consistent with a contribution of common circuitry to the processing of diverse rewards.     

Transient association of MCM complex proteins with the nuclear matrix during initiation of mammalian DNA replication

The minichromosome maintenance complex (MCM2-7) is the putative DNA helicase ineukaryotes, and essential for DNA replication. By applying serial extractions to mammaliancells synchronized by release from quiescence, we reveal dynamic changes to thesub-nuclear compartmentalization of MCM2 as cells pass through late G1 and early S phase,identifying a brief window when MCM2 becomes transiently attached to the nuclear-matrix.The data distinguish 3 states that correspond to loose association with chromatin prior toDNA replication, transient highly stable binding to the nuclear-matrix coincident withinitiation, and a post-initiation phase when MCM2 remains tightly associated withchromatin but not the nuclear-matrix. The data suggests that functional MCM complexloading takes place at the nuclear-matrix.     

An Alternative Non-Macrolide, Non-Imidazole Treatment Regimen for Curing Helicobacter pylori and Duodenal Ulcers: Ranitidine Bismuth Citrate Plus Amoxicillin

Background. Because patients who fail to be cured of H. pylori infection following macrolide or imidazole therapy are difficult to treat, there is a clear need for a reasonably effective and simple second-line treatment regimen. The purpose of these two studies was to evaluate the efficacy of ranitidine bismuth citrate (RBC) plus amoxicillin for the cure of H. pylori infection and for healing duodenal ulcers and preventing ulcer relapse.
Materials and Methods. Two identically designed randomized, double-blind, double-dummy studies were conducted in patients with an H. pylori -associated duodenal ulcer. Patients were treated with either RBC 400 mg bid for 4 weeks plus amoxicillin 500 mg qid for 2 weeks, RBC 400 mg bid for 4 weeks and placebo qid for 2 weeks, placebo bid for 4 weeks and amoxicillin 500 mg qid for 2 weeks, or placebo bid for 4 weeks and placebo qid for 2 weeks. Patients with healed ulcers after 4 weeks of treatment were eligible for entry into a 24-week observation phase for the assessment of H. pylori status (culture, histology, and CLOtest^TM) and ulcer relapse.
Results. A total of 229 patients with confirmed H. pylori infection at baseline were evaluated. Of these, 132 whose ulcers had healed entered the 24-week posttreatment observation phase. The combination of RBC plus amoxicillin resulted in higher H. pylori cure rates (55%) and higher duodenal ulcer healing (74%) than did either treatment alone. All treatments were well tolerated.
Conclusions. The combination of ranitidine bismuth citrate plus amoxicillin cures H. pylori infection in more than half of the patients treated. This treatment regimen shows promise as the basis for future non-macrolide, non-imidazole triple therapy regimens for curing H. pylori infection. Such regimens may be appropriate second-line treatment for patients who are resistant to or who are unable to tolerate macrolide- or imidazole-containing therapies.     

The molecular structure of the high potential iron-sulfur protein isolated from Ectothiorhodospira halophila determined at 2.5-A resolution

The molecular structure of a high potential iron-sulfur protein (HiPIP) isolated from the purple photosynthetic bacterium, Ectothiorhodospira halophila strain BN9626, has been solved by x-ray diffraction analysis to a nominal resolution of 2.5 A and refined to a crystallographic R value of 18.4% including all measured x-ray data from 30.0- to 2.5-A resolution. Crystals used in the investigation contained two molecules/asymmetric unit and belonged to the space group P21 with unit cell dimensions of a = 60.00 A, b = 31.94 A, c = 40.27 A, and beta = 100.5 degrees. An interpretable electron density map, obtained by combining x-ray data from one isomorphous heavy atom derivative with non-crystallographic symmetry averaging and solvent flattening, clearly showed that this high potential iron-sulfur protein contains 71 amino acid residues, rather than 70 as originally reported. As in other bacterial ferredoxins, the [4Fe-4S] cluster adopts a cubane-like conformation and is ligated to the protein via four cysteinyl sulfur ligands. The overall secondary structure of the E. halophila HiPIP is characterized by a series of Type I and Type II turns allowing the polypeptide chain to wrap around the [4Fe-4S] prosthetic group. The hydrogen bonding pattern around the cluster is nearly identical to that originally observed in the 85-amino acid residue Chromatium vinosum HiPIP and consequently, the 240 mV difference in redox potentials between these two proteins cannot be simply attributed to hydrogen bonding patterns alone.     

Enhanced antitumor responses elicited by combinatorial protein transfer of chemotactic and costimulatory molecules

Thus far, immunotherapies based on one or a few immunostimulatory molecules have shown limited antitumor efficacy. This highlights the need to use multiple immunostimulatory molecules, to target different immune cells, including immunosuppressive cells, simultaneously. Consequently, in this study, we delivered intratumorally via protein transfer four molecules, including the chemotactic molecules secondary lymphoid tissue chemokine and Fas ligand and the costimulatory molecules 4-1BBL and TNF-related activation-induced cytokine. Secondary lymphoid tissue chemokine and Fas ligand together can attract an array of immune cells and induce apoptosis in CD4(+)CD25(+) regulatory T cells (Treg), whereas 4-1BBL and TRANCE together can stimulate T cells and dendritic cells (DCs). We show that the transfer of all four molecules increases tumor-infiltrating neutrophils, DCs, and CD4(+) and CD8(+) T cells and decreases intratumoral Treg. We show that the treatment favors the generation of a Th1 cytokine milieu at the tumor site, which is attributed not only to an increase in IL-12-producting DCs and IFN-gamma-producing CD8(+) T cells, but also to a decrease in IL-10-producing Treg. Importantly, in the L5178Y lymphoma model, we show that compared with transfer of the chemotactic molecules alone or the costimulatory molecules alone, transfer of all four molecules demonstrates stronger antitumor responses against established tumors. Furthermore, we show that the antitumor responses elicited by transfer of all four molecules are mediated by long-term, systemic antitumor immunity. Hence, this study demonstrates for the first time that combinatorial use of chemotactic and costimulatory molecules provides a useful strategy for enhancing antitumor responses.     

The Commonality of Loss Aversion across Procedures and Stimuli

Individuals tend to give losses approximately 2-fold the weight that they give gains. Such approximations of loss aversion (LA) are almost always measured in the stimulus domain of money, rather than objects or pictures. Recent work on preference-based decision-making with a schedule-less keypress task (relative preference theory, RPT) has provided a mathematical formulation for LA similar to that in prospect theory (PT), but makes no parametric assumptions in the computation of LA, uses a variable tied to communication theory (i.e., the Shannon entropy or information), and works readily with non-monetary stimuli. We evaluated if these distinct frameworks described similar LA in healthy subjects, and found that LA during the anticipation phase of the PT-based task correlated significantly with LA related to the RPT-based task. Given the ease with which non-monetary stimuli can be used on the Internet, or in animal studies, these findings open an extensive range of applications for the study of loss aversion. Furthermore, the emergence of methodology that can be used to measure preference for both social stimuli and money brings a common framework to the evaluation of preference in both social psychology and behavioral economics.