Subgoal- and goal-related reward prediction errors in medial prefrontal cortex

A longstanding view of the organization of human and animal behavior holds that behavior is hierarchically organizedin other words, directed toward achieving superordinate goals through the achievement of subordinate goals or subgoals. However, most research in neuroscience has focused on tasks without hierarchical structure. In past work, we have shown that negative reward prediction error (RPE) signals in medial prefrontal cortex (mPFC) can be linked not only to superordinate goals but also to subgoals. This suggests that mPFC tracks impediments in the progression toward subgoals. Using fMRI of human participants engaged in a hierarchical navigation task, here we found that mPFC also processes positive prediction errors at the level of subgoals, indicating that this brain region is sensitive to advances in subgoal completion. However, when subgoal RPEs were elicited alongside with goal-related RPEs, mPFC responses reflected only the goal-related RPEs. These findings suggest that information from different levels of hierarchy is processed selectively, depending on the task context

Long-term interleukin-6 levels and subsequent risk of coronary heart disease: Two new prospective studies and a systematic review

Background The relevance to coronary heart disease (CHD) of cytokines that govern inflammatory cascades, such as interleukin-6 (IL-6), may be underestimated because such mediators are short acting and prone to fluctuations. We evaluated associations of long-term circulating IL-6 levels with CHD risk (defined as nonfatal myocardial infarction [MI] or fatal CHD) in two population-based cohorts, involving serial measurements to enable correction for within-person variability. We updated a systematic review to put the new findings in context. Methods and Findings Measurements were made in samples obtained at baseline from 2,138 patients who had a first-ever nonfatal MI or died of CHD during follow-up, and from 4,267 controls in two cohorts comprising 24,230 participants. Correction for within-person variability was made using data from repeat measurements taken several years apart in several hundred participants. The year-to-year variability of IL-6 values within individuals was relatively high (regression dilution ratios of 0.41, 95% confidence interval [CI] 0.28-0.53, over 4 y, and 0.35, 95% CI 0.23-0.48, over 12 y). Ignoring this variability, we found an odds ratio for CHD, adjusted for several established risk factors, of 1.46 (95% CI 1.29-1.65) per 2 standard deviation (SD) increase of baseline IL-6 values, similar to that for baseline C-reactive protein. After correction for within-person variability, the odds ratio for CHD was 2.14 (95% CI 1.45-3.15) with long-term average ("usual'') IL-6, similar to those for some established risk factors. Increasing IL-6 levels were associated with progressively increasing CHD risk. An updated systematic review of electronic databases and other sources identified 15 relevant previous population-based prospective studies of IL-6 and clinical coronary outcomes (i.e., MI or coronary death). Including the two current studies, the 17 available prospective studies gave a combined odds ratio of 1.61 (95% CI 1.42-1.83) per 2 SD increase in baseline IL-6 (corresponding to an odds ratio of 3.34 [95% CI 2.45-4.56] per 2 SD increase in usual [long-term average] IL-6 levels). Conclusions Long-term IL-6 levels are associated with CHD risk about as strongly as are some major established risk factors, but causality remains uncertain. These findings highlight the potential relevance of IL-6-mediated pathways to CH

A combination of GFRP sheets and steel cage for seismic strengthening of shear-deficient corner RC beam-column joints

International Institute of Earthquake Engineering and Seismology (IEES), project number 7342

A combination of GFRP sheets and steel cage for seismic strengthening of shear-deficient corner RC beam-column joints

International Institute of Earthquake Engineering and Seismology (IEES), project number 7342

Effect of non-fiber carbohydrates on in vitro first order kinetics disappearance of cellulose

Summary An in vitro experiment was conducted to determine the effect of supplemental non-fiber carbohydrate (NFC) on the disappearance kinetics of cellulose (Ce) by mixed ruminal microorganisms. Non-supplemented or NFC supplemented cellulose (467 mg NFC/g cellulose as sucrose (CeSu) or starch (CeSt) or a 1:1 mixture of sucrose + starch (CeSuSt)) were incubated for 24, 48, and 96 h at 39°C. After each incubation time, pH, ammonia-N concentration and cellulose disappearance were measured. The disappearance kinetics rate of all samples was determined using first order exponential model of D (t) = D (i) .exp (-k. time) + I; where D (t) is potentially digestible fraction; D (i) is potentially digestible residues; k is digestion rate of cellulose (h -1 ) and I is indigestible fraction. In this experiment, inclusion of NFC to the rumen fluid medium resulted in a significant depression (P<0.01) in the extent of cellulose disappearance. The disappearance rate constant of cellulose was significantly higher (P<0.05) in non-supplemented samples as compared with those treatments containing NFC. The indigestible fraction of cellulose was significantly higher (P<0.05) for treatments containing sucrose or sucrose + starch as the source of supplemental NFC as compared with nonsupplemented cellulose. However, when starch was added, the indigestible fraction of cellulose was similar to those of non-supplemented samples. The inclusion of NFC resulted in a significant reduction (P<0.01) in pH of the medium, but had no significant effect (P>0.05) on ammonia-N concentration

Human midcingulate cortex encodes distributed representations of task progress

The function of midcingulate cortex (MCC) remains elusive despite decades of investigation and debate. Complicating matters, individual MCC neurons respond to highly diverse task-related events, and MCC activation is reported in most human neuroimaging studies employing a wide variety of task manipulations. Here we investigate this issue by applying a model-based cognitive neuroscience approach involving neural network simulations, functional magnetic resonance imaging, and representational similarity analysis. We demonstrate that human MCC encodes distributed, dynamically evolving representations of extended, goal-directed action sequences. These representations are uniquely sensitive to the stage and identity of each sequence, indicating that MCC sustains contextual information necessary for discriminating between task states. These results suggest that standard univariate approaches for analyzing MCC function overlook the major portion of task-related information encoded by this brain area and point to promising new avenues for investigation

Parthenolide: suggested drug for COVID-19

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the 2019 novel coronavirus (2019-nCoV) that causes acute respiratory distress syndrome (ARDS) which is the main reason for patients mortality. One of the effective treatments to reduce the effects of this virus is parthenolide (PN). Parthenolide is a sesquiterpene lactone found in medicinal plants. It can inhibit several pro-inflammatory signaling pathways, in particular the ATPase activity of NLRP3. Based on its ability to suppress inflammatory signal transduction and elevated level of serum IL-1β (a surrogate marker for NLRP3 activation) in COVID-19 patients, we suggest that PN could be potentiallyeffective for the treatment of COVID-19

ATPS as an Efficient Method for Separation of Bionanoparticles: Investigation and Optimization of Partition Behavior of pDNA

In this paper, the efficiency of an aqueous two-phase system (ATPS) for purification of nanometer-sized bioparticles, plasmid DNA (pDNA), was studied. Polymer-salt ATPS consisting of polyethylenglycol (PEG)-K2HPO4 was used for the purification of 7 kb and 14 kb plasmid vectors. PEG-300 and PEG-1450 were applied to investigate the influence of different molecular mass of PEGon partitioning behavior of pDNA. The Taguchi design of experiments has been applied in order to optimize the significant system characteristics including PEG/salt ratio, temperature, lysate mass fraction and size of plasmid for pDNA separation by using ATPS. The results indicated that PEG/salt ratio has a considerable contribution on pDNA recovery both in the presence of PEG-300 and PEG-1450. It is also obtained that the size of pDNA in the range of 7 kb to 14 kb is not a significant factor on its partitioning. Furthermore, pDNA is easily partitioned to polymer-rich top phase in PEG300/salt system; and in salt-rich bottom phase in PEG1450/salt system. Under optimum conditions, pDNA was extracted in top phase of PEG-300/K2HPO4 with mass percent of 26 : 17 at 25 °C with a recovery percent of 85

Helicobacter pylori and cancer among adults in Uganda

Data from Africa on infection with Helicobacter pylori (H. pylori) are sparse. Therefore, as part of an epidemiological study of cancer in Uganda, we investigated the prevalence and determinants of antibodies against H. pylori among 854 people with different cancer types and benign tumours. Patients were recruited from hospitals in Kampala, Uganda, interviewed about various demographic and lifestyle factors and tested for antibodies against H. pylori. In all patients combined, excluding those with stomach cancer (which has been associated with H. pylori infection), the prevalence of antibodies was 87% (723/833) overall, but declined with increasing age (p = 0.02) and was lower among people who were HIV seropositive compared to seronegative (p <0.001). Otherwise, there were few consistent epidemiological associations. Among those with stomach cancer, 18/21 (86%) had anti-H. pylori antibodies (odds ratio 0.8, 95% confidence intervals 0.2–2.9, p = 0.7; estimated using all other patients as controls, with adjustment for age, sex and HIV serostatus). No other cancer site or type was significantly associated with anti-H. pylori antibodies. The prevalence of H. pylori reported here is broadly in accord with results from other developing countries, although the determinants of infection and its' role in the aetiology of gastric cancer in Uganda remain unclear