Miracle-dz/UniFAR-FTUs huggingface dataset:
Serotonin selectively influences moral judgment and behavior through effects on harm aversion

Aversive emotional reactions to real or imagined social harms infuse moral judgment and motivate prosocial behavior. Here, we show that the neurotransmitter serotonin directly alters both moral judgment and behavior through increasing subjects’ aversion to personally harming others. We enhanced serotonin in healthy volunteers with citalopram (a selective serotonin reuptake inhibitor) and contrasted its effects with both a pharmacological control treatment and a placebo on tests of moral judgment and behavior. We measured the drugs' effects on moral judgment in a set of moral 'dilemmas' pitting utilitarian outcomes (e.g., saving five lives) against highly aversive harmful actions (e.g., killing an innocent person). Enhancing serotonin made subjects more likely to judge harmful actions as forbidden, but only in cases where harms were emotionally salient. This harm-avoidant bias after citalopram was also evident in behavior during the ultimatum game, in which subjects decide to accept or reject fair or unfair monetary offers from another player. Rejecting unfair offers enforces a fairness norm but also harms the other player financially. Enhancing serotonin made subjects less likely to reject unfair offers. Furthermore, the prosocial effects of citalopram varied as a function of trait empathy. Individuals high in trait empathy showed stronger effects of citalopram on moral judgment and behavior than individuals low in trait empathy. Together, these findings provide unique evidence that serotonin could promote prosocial behavior by enhancing harm aversion, a prosocial sentiment that directly affects both moral judgment and moral behavior.
S1-DRIP-seq identifies high expression and polyA tracts as major contributors to R-loop formation

In this study, Wahba et al. investigate how and where DNA–RNA hybrids, which form when an RNA molecule hybridizes to the complementary genomic locus, appear throughout the genome. They present a novel whole-genome method, S1-DRIP-seq, for mapping hybrid-prone regions in S. cerevisiae and identify the first global genomic features that play a causal role in R-loop formation in yeast.
Prefrontal cortex in the rat: Projections to subcortical autonomic, motor, and limbic centers

This paper describes the quantitative areal and laminar distribution of identified neuron populations projecting from areas of prefrontal cortex (PFC) to subcortical autonomic, motor, and limbic sites in the rat. Injections of the retrograde pathway tracer wheat germ agglutinin conjugated with horseradish peroxidase (WGA‐HRP) were made into dorsal/ventral striatum (DS/VS), basolateral amygdala (BLA), mediodorsal thalamus (MD), lateral hypothalamus (LH), mediolateral septum, dorsolateral periaqueductal gray, dorsal raphe, ventral tegmental area, parabrachial nucleus, nucleus tractus solitarius, rostral/caudal ventrolateral medulla, or thoracic spinal cord (SC). High‐resolution flat‐map density distributions of retrogradely labelled neurons indicated that specific PFC regions were differentially involved in the projections studied, with medial (m)PFC divided into dorsal and ventral sectors. The percentages that WGA‐HRP retrogradely labelled neurons composed of the projection neurons in individual layers of infralimbic (IL; area 25) prelimbic (PL; area 32), and dorsal anterior cingulate (ACd; area 24b) cortices were calculated. Among layer 5 pyramidal cells, approximately 27.4% in IL/PL/ACd cortices projected to LH, 22.9% in IL/ventral PL to VS, 18.3% in ACd/dorsal PL to DS, and 8.1% in areas IL/PL to BLA; and 37% of layer 6 pyramidal cells in IL/PL/ACd projected to MD. Data for other projection pathways are given. Multiple dual retrograde fluorescent tracing studies indicated that moderate populations (<9%) of layer 5 mPFC neurons projected to LH/VS, LH/SC, or VS/BLA. The data provide new quantitative information concerning the density and distribution of neurons involved in identified projection pathways from defined areas of the rat PFC to specific subcortical targets involved in dynamic goal‐directed behavior. J. Comp. Neurol. 492:145–177, 2005. © 2005 Wiley‐Liss, Inc.
Chelidonine isolated from ethanolic extract of Chelidonium majus promotes apoptosis in HeLa cells through p38-p53 and PI3K/AKT signalling pathways.

OBJECTIVE To evaluate the role of chelidonine isolated from ethanolic extract of Chelidonium majus in inducing apoptosis in HeLa cells and to assess the main signalling pathways involved. METHODS Cells were initially treated with different concentrations of chelidonine for 48 h and the median lethal dose (LD50) value was selected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Morphological analysis of nuclear condensation and DNA damage and fragmentation were measured by 4',6-diamidino-2-phenylindole staining and comet assay. Further, reactive oxygen species (ROS) generation, cell cycle arrest and change in mitochondrial membrane potential were also examined and analyzed by flow cytometry. Evaluation of interaction of drug with CT DNA was investigated by circular dichroism (CD) spectral analysis to find any possible drug-CT DNA interaction. The mRNA and protein expressions of major signal proteins like p38, p53, protein kinase B (AKT), phosphatidylinositol 3-kinases (PI3K), Janus kinase 3 (JAK3), signal transducer and activator of transcription 3 (STAT3) and E6 and E7 oncoproteins as well as the pro-apoptotic genes and antiapoptotic genes were also estimated by reverse transcriptase-polymerase chain reaction and Western blotting. RESULTS Based on LD(50) value (30 μg/mL) of chelidonine, three doses were selected, namely, 22.5 μg/mL (D1), 30.0 μg/mL (D2) and 37.5 μg/mL (D3). Results showed that chelidonine inhibited proliferation and induced apoptosis in HeLa cells through generation of ROS, cell cycle arrest at sub-G1 and G0/G1 stage, change in mitochondrial membrane potential and fragmentation of DNA. Results of CD spectra showed effective interaction between chelidonine and calf thymus DNA. Studies of signalling pathway revealed that chelidonine could efficiently induce apoptosis through up-regulation of expressions of p38, p53 and other pro-apoptotic genes and down-regulation of expressions of AKT, PI3K, JAK3, STAT3, E6, E7 and other antiapoptotic genes. CONCLUSION Chelidonine isolated from Chelidonium majus efficiently induced apoptosis in HeLa cells through possible alteration of p38-p53 and AKT/PI3 kinase signalling pathways.
Repetitive Hypoglycemia in Young Rats Impairs Hippocampal Long-Term Potentiation

Mechanisms underlying cognitive dysfunction in young diabetic children are poorly understood, and may include synaptic dysfunction from insulin-induced hypoglycemia. We developed a model of repetitive insulin-induced hypoglycemia in young rats and examined hippocampal long-term potentiation, an electrophysiologic assay of synaptic plasticity, 3–5 d after the last hypoglycemic event. Three hypoglycemic events between postnatal d 21–25 produced modest cortical (17 ± 2.9 dead neurons per section in parasagittal cortex), but not hippocampal, neuron death quantified by Fluoro-Jade B staining. There was no change in neurogenesis in the hippocampal dentate granule cell region by quantification of bromodeoxyuridine incorporation. Although normal baseline hippocampal synaptic responses were elicited from hippocampal slices from hypoglycemic animals, long-term synaptic potentiation could not be induced in hippocampal slices from rats subjected to hypoglycemia. These results suggest that repetitive hypoglycemia in the developing brain can cause selective impairment of synaptic plasticity in the absence of cell death, and without complete disruption of basal synaptic transmission. We speculate that impaired synaptic plasticity in the hippocampus caused by repetitive hypoglycemia could underlie memory and cognitive deficits observed in young diabetic children, and that cortical neuron death caused by repetitive hypoglycemia in the developing brain may contribute to other neurologic, cognitive, and psychological problems sometimes encountered in diabetic children.
Predictors for quality of life in continuous ambulatory peritoneal dialysis patients

Aim: Peritoneal dialysis patients have diminished quality of life scores compared with healthy subjects. Measures of quality of life have been reported to have a significant predictive value for patient survival and hospitalization in peritoneal dialysis patients. The purpose of this study is to determine the clinical, biochemical and psychological predictors for the quality of life in continuous ambulatory peritoneal dialysis (CAPD) patients.
Quantification of the physiological loading of one week of “pre-season” and one week of “in-season” training in professional soccer players

Abstract The aim of this study was to quantify the physiological loads of programmed “pre-season” and “in-season” training in professional soccer players. Data for players during each period were included for analysis (pre-season, n = 12; in-season, n = 10). We monitored physiological loading of training by measuring heart rate and rating of perceived exertion (RPE). Training loads were calculated by multiplying RPE score by the duration of training sessions. Each session was sub-categorized as physical, technical/tactical, physical and technical/tactical training. Average physiological loads in pre-season (heart rate 124 ± 7 beats · min−1; training load 4343 ± 329 Borg scale · min) were higher compared with in-season (heart rate 112 ± 7 beats · min−1; training load 1703 ± 173 Borg scale · min) (P < 0.05) and there was a greater proportion of time spent in 80–100% maximum heart rate zones (18 ± 2 vs. 5 ± 2%; P < 0.05). Such differences appear attributable to the higher intensities in technical/tactical sessions during pre-season (pre-season: heart rate 137 ± 8 beats · min−1; training load 321 ± 23 Borg scale · min; in-season: heart rate 114 ± 9 beats · min−1; training load 174 ± 27 Borg scale · min; P < 0.05). These findings demonstrate that pre-season training is more intense than in-season training. Such data indicate that these adjustments in load are a direct attempt to deliver training to promote specific training adaptations.
Stereotactic Ablative Radiotherapy for Patients with Unresectable or Medically Inoperable Cholangiocarcinoma

Purpose The role of stereotactic ablative radiotherapy (SABR) in patients with unresectable or medically inoperable cholangiocarcinoma remains unclear. We examined the efficacy and safety of SABR in this group of patients. Methods From January 2008 to December 2014, 15 patients with 17 lesions were included in this study. The lesions included 14 intrahepatic, 1 hilar, and 2 distal bile duct tumors. Three patients were classified as medically inoperable because of old age or multiple comorbidities. Tumors measured 0.8-13 cm (median, 3.6 cm). The median prescribed dose was 45 Gy delivered in 5 fractions over 5 consecutive days. Results The median follow-up period for surviving patients was 29.9 months. Objective responses were observed for 10 of 17 tumors (58.8%), including 3 complete responses (17.6%). The median survival duration was 12.6 months, and the 1- and 2-year overall survival rates were 50.3% and 14.4%, respectively. The 1- and 2-year in-field failure-free rates were 61.5% and 30.8%, respectively. For patients with biologically effective doses (BEDs) exceeding 75 Gy10, the 1- and 2-year overall survival rates were 58.3% and 33.3%, respectively, compared to 20.0% and 0%, respectively for those with BEDs lower than 75 Gy10. Radiation-induced liver disease did not develop in any patient. Acute toxicities were generally mild and tolerable. Conclusions Stereotactic ablative radiotherapy could be an alternative treatment for unresectable or medically inoperable cholangiocarcinoma. Further dose escalation may be considered to optimize local control.
Rab6‐Mediated Retrograde Transport Regulates Inner Nuclear Membrane Targeting of Caveolin‐2 in Response to Insulin

Here, we have identified a retrograde transport pathway of caveolin‐2 (cav‐2) for its regulatory function in the nucleus. Confocal microscopy analysis, photoactivation experiments and subcellular fractionation revealed that cav‐2 localized in the Golgi was transported to the inner nuclear membrane (INM) in response to insulin. Exogenous caveolin‐1 (cav‐1) and P132L‐cav‐1 expression did not affect the Golgi localization and insulin‐induced INM targeting of cav‐2. Cav‐2DKV mutant in the endoplasmic reticulum (ER) was unable to translocate to the INM in response to insulin. The GTP‐bound form of Rab6 promoted, but Rab6 siRNA and the GDP‐bound form of Rab6 abrogated, retrograde trafficking of cav‐2 from the Golgi to ER. Colchicine or nocodazole treatment abolished insulin‐induced INM targeting of cav‐2. Knock down of gp210 inhibited insulin‐induced import of cav‐2 from ER/outer nuclear membrane (ONM) to the INM. The INM‐targeted cav‐2 prevented heterochromatinization and promoted transcriptional activation of Elk‐1 and signal transducer and activator of transcription 3 (STAT3). The results provide molecular mechanisms for insulin‐induced INM translocation of cav‐2 initiated (i) by Golgi‐to‐ER retrograde trafficking of cav‐2 via microtubule‐based Rab6‐GTP‐dependent transport and subsequently processed (ii) by gp210‐mediated import of cav‐2 from ER/ONM to INM.
The TCF1-Bcl6 axis counteracts type I interferon to repress exhaustion and maintain T cell stemness

The transcription factor TCF1 determines the degree of CD8+ T cell exhaustion in chronic infection. TCF1 fine-tunes T cell exhaustion Exhaustion of CD8+ T cells is observed in chronic viral infections and in the tumor microenvironment. Using chronic LCMV infection in mice, Wu et al. report that expression levels of the transcription factor T cell factor 1 (TCF1) determine the degree of T cell exhaustion. TCF1high CD8+ T cells are less exhausted as compared with TCF1low CD8+ T cells, and they play an essential role in controlling viremia in chronically infected mice. Blockade of type I interferon, a driver of T cell exhaustion, promoted expansion of TCF1high CD8+ Tcells. The studies have better defined the molecular features of exhausted T cells and suggest that targeting TCF1-driven pathways could be used to modulate T cell exhaustion. During chronic viral infections and in cancer, T cells become dysfunctional, a state known as T cell exhaustion. Although it is well recognized that memory CD8 T cells account for the persistence of CD8 T cell immunity after acute infection, how exhausted T cells persist remains less clear. Using chronic infection with lymphocytic choriomeningitis virus clone 13 and tumor samples, we demonstrate that CD8 T cells differentiate into a less exhausted TCF1high and a more exhausted TCF1low population. Virus-specific TCF1high CD8 T cells, which resemble T follicular helper (TFH) cells, persist and recall better than do TCF1low cells and act as progenitor cells to replenish TCF1low cells. We show that TCF1 is both necessary and sufficient to support this progenitor-like CD8 subset, whereas cell-intrinsic type I interferon signaling suppresses their differentiation. Accordingly, cell-intrinsic TCF1 deficiency led to a loss of these progenitor CD8 T cells, sharp contraction of virus-specific T cells, and uncontrolled viremia. Mechanistically, TCF1 repressed several pro-exhaustion factors and induced Bcl6 in CD8 T cells, which promoted the progenitor fate. We propose that the TCF1-Bcl6 axis counteracts type I interferon to repress T cell exhaustion and maintain T cell stemness, which is critical for persistent antiviral CD8 T cell responses in chronic infection. These findings provide insight into the requirements for persistence of T cell immune responses in the face of exhaustion and suggest mechanisms by which effective T cell–mediated immunity may be enhanced during chronic infections and cancer.
Prognostic value, kinetics and effect of CVVHDF on serum of the myoglobin and creatine kinase in critically ill patients with rhabdomyolysis

Background: (I) To investigate the kinetics of the myoglobin and creatine kinase (CK) in rhabdomyolysis. Especially to describe those patients in whom an isolated increase in the myoglobin or the CK occurred at a later stage. (II) To evaluate the sensitivity of the myoglobin and the CK as prognostic tools for the development of Acute renal failure (ARF). (III) To investigate the effect of continuous venovenous haemodiafiltration (CVVHDF) on the myoglobin elimination in ARF.
Long-term assessment of psychological well-being in a randomized placebo-controlled trial of cholesterol reduction with pravastatin. The LIPID Study Investigators.

BACKGROUND There is controversial evidence that a low serum cholesterol level is associated with an increased risk of depression, suicide, and violence. The aim of this study was to identify or exclude any small or infrequent adverse effect of long-term reduction of serum cholesterol with pravastatin sodium on psychological well-being. METHODS The study population consisted of 1130 respondents from a representative sample of 1222 patients with stable coronary artery disease participating in the Long-term Intervention with Pravastatin in Ischaemic Disease (LIPID) study. Subjects were randomized in a double-blind manner to treatment with pravastatin sodium, 40 mg/d (n = 559), or placebo (n = 571) for at least 4 years. Psychological well-being was assessed with a standard self-administered questionnaire at baseline and after 6 months, 1 year, 2 years, and 4 years. The questionnaire assessed anxiety and depression, anger, impulsiveness, alcohol consumption, and adverse life events. RESULTS Serum cholesterol levels decreased by an average of 1.3 mmol/L (50 mg/dL) with pravastatin therapy and did not change with placebo. During follow-up there was no significant difference by treatment group in measures of anxiety and depression, anger expression, or impulsiveness (95% confidence interval excluded differences of >0.2 SD) and no difference in the proportion of subjects with excessive alcohol consumption or adverse life events (odds ratio, 1.0; 95% confidence interval, 0.8-1.2). There was no evidence of a treatment effect for persons whose baseline serum cholesterol level was in the lowest 10% (<4.6 mmol/L [178 mg/dL]) or whose scores for anxiety and depression, anger, or impulsiveness were in the highest 10% at baseline. There was no association between change in the serum cholesterol level and measures of anxiety and depression, anger, or impulsiveness during follow-up. CONCLUSION Long-term reduction of serum cholesterol with pravastatin has no adverse effect on psychological well-being.
Incidence of ulcerative keratitis in a defined population from 1950 through 1988.

OBJECTIVE To determine the incidence of ulcerative keratitis and to assess trends in risk factors leading to ulcerative keratitis. DESIGN Retrospective incidence cohort study. SETTING General community. PATIENTS Population-based sample of residents of Olmsted County, Minnesota, in the 39-year period between 1950 and 1988. MAIN OUTCOME MEASURE Cases of ulcerative keratitis. RESULTS One hundred forty-one cases of ulcerative keratitis were diagnosed among 131 residents (64 men and 67 women) of Olmsted County. The mean annual age-adjusted incidence per 100,000 people was 5.3 (95% confidence interval, 4.4 to 6.2). A 435% increase in the incidence of ulcerative keratitis was observed in Olmsted County residents from the 1950s (2.5 per 100,000 people) to the 1980s (11.0 per 100,000 people) (P = .001). The cases of ulcerative keratitis associated with contact lens wear increased from 0% in the 1950s and 1960s to 32% in the 1970s and 52% in the 1980s. CONCLUSION The incidence of ulcerative keratitis has increased significantly in this community. Contact lens wear was the most important risk factor for the development of ulcerative keratitis during the last decade.
Synthetic Scrapie Infectivity: Interaction between Recombinant PrP and Scrapie Brain-Derived RNA

The key molecular event in human cerebral proteinopathies, which include Alzheimer's, Parkinson's and Huntington's diseases, is the structural conversion of a specific host protein into a β-sheet-rich conformer. With regards to this common mechanism, it appears difficult to explain the outstanding infectious properties attributed to PrPSc, the hallmark of another intriguing family of cerebral proteinopathies known as transmissible spongiform encephalopathies (TSE) or prion diseases. The infectious PrPSc or "prion" is thought to be composed solely of a misfolded form of the otherwise harmless cellular prion protein (PrPc). To gain insight into this unique situation, we used the 263K scrapie hamster model to search for a putative PrPSc-associated factor that contributes to the infectivity of PrPSc amyloid. In a rigorously controlled set of experiments that included several bioassays, we showed that originally innocuous recombinant prion protein (recPrP) equivalent to PrPc is capable of initiating prion disease in hamsters when it is converted to a prion-like conformation (β-sheet-rich) in the presence of RNA purified from scrapie-associated fibril (SAF) preparations. Analysis of the recPrP-RNA infectious mixture reveals the presence of 2 populations of small RNAs of approximately 27 and 55 nucleotides. These unprecedented findings are discussed in light of the distinct relationship that may exist between this RNA material and the 2 biological properties, infectivity and strain features, attributed to prion amyloid.
Late Presenters in an HIV Surveillance System in Italy During the Period 1992-2006

Objectives:The objectives of this study are to describe trends over time from 1992 to 2006 in the number of newly diagnosed HIV-infected individuals in Modena (Italy) and to describe their clinical and immunological characteristics. We also identify risk factors associated with presenting at late stages of HIV disease. Methods:All new HIV diagnoses with at least 1 CD4+ cell count and known stage of HIV disease were included. Using multivariate logistic regression models, we examined factors associated with being a late presenter, defined as individuals presenting with CD4+ cell count <200 cells per microliter or AIDS within 3 months of their HIV-positive test. A quantile regression model was used to examine changes in CD4+ cell count at presentation and trends over time. Results:Of 844 newly diagnosed individuals included in analyses, 332 (39%) were late presenters, and this proportion remained constant over time (P = 0.106). Older age, male sex, and foreign born were the only determinants of being a late presenter. Persons newly diagnosed in 2002-2006 were less likely to present with an advanced clinical status. Discussion:A substantial proportion of new HIV diagnoses are still at advanced stages of disease. In particular, foreign-born and heterosexual males still represent the largest part of AIDS presenters. Efforts are needed to encourage HIV testing and reduce the proportion who first seek HIV care at such a late stage.