“The paramyxovirus entry machinery consists of two glycopr


“The paramyxovirus entry machinery consists of two glycoproteins that tightly cooperate to achieve membrane fusion for cell entry: the tetrameric attachment protein (HN, H, or G, depending on the paramyxovirus genus) and the trimeric fusion protein (F). Here, we explore whether receptor-induced conformational changes within morbillivirus H proteins promote membrane fusion by a mechanism requiring the active destabilization of prefusion F or by the dissociation of prefusion F from intracellularly

preformed glycoprotein complexes. To properly probe F conformations, we identified anti-F monoclonal antibodies (MAbs) that recognize conformation-dependent epitopes. Through heat treatment as a surrogate for H-mediated F triggering, we demonstrate with these MAbs that the morbillivirus F trimer contains a sufficiently high inherent Danusertib order activation energy barrier to maintain the metastable prefusion BMS-754807 supplier state even in the absence of H. This notion was further validated by exploring the conformational states of destabilized F mutants and stabilized soluble F variants combined with the use of a membrane fusion inhibitor (3g). Taken together, our findings reveal that the morbillivirus

H protein must lower the activation energy barrier of metastable prefusion F for fusion triggering.”
“The computational simulation of complete proteomic data sets and their utility to validate detection and interpretation algorithms, to aid in the design of experiments and to assess protein and peptide false discovery rates is presented. The simulation software has been developed for emulating data originating from data-dependent and data-independent LC-MS workflows. Data check details from all types of commonly used hybrid mass spectrometers can be simulated. The algorithms are based on empirically derived physicochemical liquid and gas phase models for proteins and peptides. Sample composition in terms of complexity and dynamic range, as well as chromatographic, experimental and MS conditions, can be controlled and

adjusted independently. The effect of on-column amounts, gradient length, mass resolution and ion mobility on search specificity will be demonstrated using tryptic peptides from human and yeast cellular lysates simulated over five orders of magnitude in dynamic range. Initial justification of the simulated data sets is achieved by comparing and contrasting the in silico simulated data to experimentally derived results from a 48 protein mixture, spanning a similar magnitude of five orders of magnitude. Additionally, experimental data from replicate and dilutions series experiments will be utilized to determine error rates at the peptide and protein level with respect to mass, area, retention and drift time. The data presented reveal a high degree of similarity at the ion detection, peptide and protein level when analyzed under similar conditions.

6% Lifetime risk was higher in men than in women (29 7% vs 25 6%

6%. Lifetime risk was higher in men than in women (29.7% vs 25.6%), individuals of lower socioeconomic status than in SB203580 concentration those of higher socioeconomic status (32.1% vs 23.0%), and individuals who lived in a rural setting than in those who lived in an urban setting (32.4% vs 26.7%).

Interpretation About one in four individuals are likely to be diagnosed and receive medical attention for COPD during their lifetime. Clinical evidence-based approaches, public health action, and more research are needed to identify effective

strategies to prevent COPD and ensure that those with the disease have the highest quality of life possible.”
“Studies to understand the pathogenesis of obesity have revealed mediators that are responsible for the control of food intake and metabolism at the hypothalamic level. However, molecular insight explaining the link between obesity and low-degree chronic inflammation remains elusive. The adipocyte-derived hormone leptin, and thereby the nutritional status, could control immune self-tolerance by affecting regulatory T (Treg) cell responsiveness and function. Furthermore, DNA Synthesis inhibitor resident Treg cells, which are capable of modulating metabolism and glucose homeostasis, are abundant in adipose tissue. Here, we provide an update on recent findings relating Treg cells to obesity

and discuss how the intricate network of interactions among leptin, Treg cells and adipose tissue might provide new strategies for therapeutic interventions.”
“Behavioral and neurophysiological studies have shown an enhancement of visual perception in crossmodal audiovisual stimulation conditions, CA-4948 both for sensitivity and reaction times, when the stimulation in the two sensory modalities occurs in condition of space and time congruency.

The purpose of the present work is to verify whether congruent visual and acoustic stimulations can improve the detection of visual stimuli in people affected by low vision. Participants were asked to detect the presence of a visual stimulus (yes/no task) either presented in isolation (i.e., unimodal visual stimulation) or simultaneously with auditory stimuli, which could be placed in the same spatial position (i.e., crossmodal congruent conditions) or in different spatial positions (i.e., crossmodal incongruent conditions). The results show for the first time audiovisual integration effects in low vision individuals. In particular, it has been observed a significant visual detection benefit in the crossmodal congruent as compared to the unimodal visual condition. This effect is selective for visual stimulation that occurs in the portion of visual field that is impaired, and disappears in the region of space in which vision is spared. Surprisingly, there is a marginal crossmodal benefit when the sound is presented at 16 degrees far from the visual stimulus.

6 x 10(-3) RLU cfu(-1) The mutant has a growth pattern and carbo

6 x 10(-3) RLU cfu(-1). The mutant has a growth pattern and carbofuran degradationability similar to PCL3 wild-type. The luminescent emissionby PCL3:luxAB1 directly correlated with the metabolic activity of the cells. The optimal pH, temperature and n-decanal concentration for luminescence emission are 7.0, 35 degrees C and 0.01%, respectively. PCL3:luxAB1 was used to assess the toxicity of carbofuran and carbofuran phenol in basal salt medium (BSM) in which the different sensitivity of the cells is dependent on the biomass concentration. With the luciferase

system, the degradative fraction of the augmented PCL3:luxAB1 and the difference between the active augmented PCL3:luxAB1 and indigenous microorganisms at the contaminated site could be JQ-EZ-05 price indicated.”
“After the complete

gene of a beta-galactosidase from human isolate Bifidobacterium breve B24 was isolated by PCR and overexpressed in Ipatasertib mouse E. coli, the recombinant beta-galactosidase was purified to homogeneity and characterized for the glycoside transferase (GT) and glycoside hydrolase (GH) activities on lactose. One complete ORF encoding 691 amino acids (2076 bp) was the structural gene, LacA (galA) of the beta-gal gene. The recombinant enzyme shown by activity staining and gel-filtration chromatography was composed of a homodimer of 75 kDa with a total molecular mass of 150 kDa. The Km value for lactose (95.58 mM) was 52.5-fold higher than the corresponding Km values for the synthetic substrate ONPG (1.82 mM). This enzyme with the optimum of pH 7.0 and 45 degrees C could synthesize approximately 42.00% of GOS from 1 M of lactose. About 97.00% of lactose in milk was also quickly hydrolyzed by this enzyme (50 units) at 45 degrees C for 5 h to produce 46.30% of glucose, 46.60% of galactose and 7.10% of GOS. The results suggest that this recombinant beta-galactosidase derived from a human isolate B. breve B24 may be suitable

for both the hydrolysis and synthesis of galacto-oligosaccharides Src inhibitor (GOS) in milk and lactose processing.”
“Although several xylanases have been studied, only few xylanases from marine micro-organisms have been reported. We report here a novel halotolerant xylanase from marine bacterium Bacillus subtilis cho40 isolated from Chorao island of mandovi estuary Goa, India. Extracellular xylanase was produced by using agricultural residue such as wheat bran as carbon source under solid-state fermentation (SSF). The optimal pH and temperature of xylanase were reported to be 6.0 and 60 degrees C, respectively. Xyn40 was highly salt-tolerant, and showed highest activity at 0.5 M NaCl. Xylanase activity was greatly induced (140%) when pre-incubated with 0.5 M NaCl for 4 h. The xylanase gene, xyn40, from marine bacterium B. subtilis cho40 was cloned, and expressed in Escherichia coli. The xylanase gene was 645 bp long and had a 215 amino acid ORF protein with a molecular mass of 22.9 kDa.


“Antibody to Epstein-Barr virus (EBV) early antigen diffus


“Antibody to Epstein-Barr virus (EBV) early antigen diffuse (anti-EA-D) is associated with viral replication. However, their possible associations with clinical/therapeutic features in primary Sjogren’s syndrome (pSS) were not established. We evaluated 100 pSS patients (American-European Criteria) and 89 age/gender/ethnicity-matched healthy Adriamycin controls. Disease activity was measured by EULAR Sjogren’s Syndrome Disease Activity Index (ESSDAI). Antibodies to EBV (anti-VCA IgG/IgM, anti-EBNA-1 IgG, anti-EA-D IgG) were determined by ELISA. Patients

and controls had comparable frequencies and mean levels of anti-VCA IgG (90 vs. 86.5 %, p = 0.501; 2.6 +/- A 1.1 vs. 2.5 +/- A 1.1 AU/mL, p = 0.737) and anti-EBNA-1 IgG (92 vs. 94.4 %, p = 0.576; 141.3 +/- A 69.8 vs. 135.6 +/- A 67.5 RU/mL, p = 0.464). MRT67307 Anti-VCA IgM was negative in all cases. Noteworthy, higher frequency and increased mean levels of anti-EA-D were observed in patients than controls (36 vs. 4.5 %, p < 0.0001; 38.6 +/- A 57.4 vs. 7.9 +/- A 26.3 RU/mL, p < 0.0001). Further analysis of patients with (n = 36) and without (n = 64) anti-EA-D revealed comparable age/gender/ethnicity (p a parts per thousand yen 0.551), current prednisone dose (4.8 +/- A 6.9 vs. 5.1 +/- A 10.4 mg/day, p = 0.319), and current uses of prednisone (52.8 vs. 37.5 %, p = 0.148) and immunosuppressants

(44.4 vs. 31.3 %, p = 0.201). ESSDAI values to were comparable

(p = 0.102), but joint activity was more frequent (25 vs. 9.4 %, p = 0.045) in anti-EA-D positive patients. Anti-EA-D antibodies were not associated with anti-Ro/SSA (p = 1.000), anti-La/SSB (p = 0.652), rheumatoid factor (p = 1.000), anti-alpha-fodrin (p = 0.390) or antiphospholipid antibodies (p = 0.573), not suggesting cross-reactivity. The higher anti-EA-D frequency associated with joint activity raises the possibility that a subclinical EBV reactivation may trigger or perpetuate the articular involvement in pSS.”
“Ankylosing spondylitis (AS) affects sacroiliac joints at early stages and may involve the axial skeleton at later stages of disease. Peripheral involvement usually occurs in lower extremities. When it develops early in the disease course, it is a predictor of more aggressive disease. The aim of this study is to evaluate health-related quality of life (HRQoL) in AS and to assess the impact of peripheral involvement on HRQoL domains in terms of disease activity, functional status, pain, and social and emotional functioning. Seventy-four AS patients were included. Peripheral involvement was present in 51.35 % of the patients. In 65.79 % of these cases the hips, in 31.58 % the knees, in 18.42 % the shoulders and in 13.16 % the ankles were affected.

In preventive and therapeutic models of murine colitis, administr

In preventive and therapeutic models of murine colitis, administration of GG-52 significantly reduced the severity of DSS-induced colitis, as assessed by disease activity index, colon length, and histology. In contrast, GG-50B did not show a significant reduction in the colitis severity. Moreover, the efficacy on attenuating colitis by GG-52 was comparable

to that by sulfasalazine or prednisolone. These results indicate that the novel guggulsterone derivative GG-52 blocks NF-kappa B activation in IEC and ameliorates DSS-induced acute murine colitis, which suggests that GG-52 is a potential therapeutic agent for the treatment of inflammatory bowel diseases. Laboratory Investigation (2010) 90, 1004-1015; doi: 10.1038/labinvest.2010.54; published online 1 March 2010″
“The ability to retrieve temporal and spatial context information see more from memory declines with healthy aging. The hippocampus (HC) has SU5402 research buy been shown to be associated with successful encoding and retrieval of spatio-temporal context, versus item recognition information (Davachi, Mitchell, &

Wagner, 2003; Nadel, Samsonovich, Ryan, & Moscovitch, 2000; Ross & Slotnick, 2008). Aging has been linked to volume reduction in the HC (Bouchard, Malykhin, Martin, Hanstock, Emery, Fisher, & Camicioli, 2008; Malykhin, Bouchard, Camicioli, & Coupland, 2008; Raz et al., 2005). As such, age-associated reductions in anterior HC volume may contribute to the context memory deficits observed in older adults. In the current MRI study we investigated whether item recognition, spatial context and temporal context learn more memory performance would be predicted by regional volumes in HC head (HH), body (HB) and tail (HT) volumes, using within group multiple regression analyses in a sample of 19 healthy young (mean age 24.3) and 20 older adults (mean age 67.7). We further examined between

age-group differences in the volumes of the same HC sub-regions. Multiple regression analyses revealed that in younger adults both spatial and temporal context retrieval performance was predicted by anterior HC volume. Older age was associated with significant volume reductions in HH and HB, but not HT; and with reduced ability to retrieve spatial and temporal contextual details from episodic memory. However, HC volumes did not predict context retrieval performance in older adults. We conclude that individual differences in anterior, not posterior, HC volumes predict context memory performance in young adults. With age there may be a posterior-to-anterior shift from using HC-related processes, due to HC volume loss, to employing the prefrontal cortex to aid in the performance of cognitively demanding context memory tasks. However, due to concomitant changes in the prefrontal system with age, there are limits to compensation in the aging brain. Crown Copyright (C) 2010 Published by Elsevier Ltd. All rights reserved.

Cochlear echo response amplitudes in the 2-8 kHz range and ABR wa

Cochlear echo response amplitudes in the 2-8 kHz range and ABR wave latencies, specifically wave V and interpeak interval I-V, were also significantly reduced in newborns of smoking mothers. Functional pathway analysis of upregulated placental click here genes using the Database for Annotation, Visualization and Integrated Discovery (DAVID) online software showed significant enrichment of terms associated with neurodevelopmental processes including glutamatergic and cholinergic systems and a number of wingless type proteins in the top two tiers with corrected

enrichment p-values of <= 0.05. Other relevant functional pathways were significant at unadjusted enrichment p-values of 0.001-0.11 and included calcium signaling, neurotransmission/neurological processes and oxidative stress. The neurological process clusters included 7 genes (EML2, OTOR, SLC26A5, TBL1X, TECTA, USH1C and USH1G) known to modulate cochlear outer hair cell

motility. We localized proteins encoded by the top two regulated genes, TBL1X and USH1C, using immunohistochemistry to placental stem and anchoring villi associated with active contractile Sorafenib chemical structure function. These placental genes may mediate active contraction and relaxation in the placental villi, for example, during maternal-fetal perfusion matching, similar to the active lengthening and shortening of the cochlear outer hair cells during sensory transduction. Thus, the functional consequence of their alteration in the cochlea would be reflected as a decline in cochlear echoes as shown in this study. Such parallel changes suggest the potential utility of placental gene expression as a surrogate for evaluating changes in the developing cochlea related to potential aberrant cochlear function in newborns with prenatal smoke exposure. (C) 2013 Elsevier Inc. All rights reserved.”
“Polymerase chain reaction (PCR) assays allow for

the rapid and accurate detection of infectious agents through identification selleck compound of nucleic acid sequences. However, contamination of samples with positive DNA can lead to false-positive results. In this study, positive control plasmids were developed to minimize false-positive reactions due to PCR contamination during detection of SVCV by semi-nested reverse-transcription PCR. An ampicillin resistance gene was truncated by PCR amplification, and the fragments were inserted into pGEM-T Easy vectors; the resulting plasmids were named SVCV chimeric plasmid-1 and chimeric plasmid-2, respectively. Through a series of semi-nested PCRs, the use of SVCV chimeric plasmids-1 and -2 was shown to ensure correct diagnoses, free from PCR contamination. The results of this study show that PCR positive controls can be created without use of viral nucleic acids or pathogen-infected tissues. The technique can be applied to quarantined material and can be used to detect other pathogens.

The amount of virus

The amount of virus LRRK2 inhibitor was determined using specific primers and probe and standardised to the amount of DNA present in each sample, using selected endogenous tomato or Bemisia genes as internal references. The distribution of TYLCSV was relatively quantified within the four uppermost leaves of plants. An absolute estimation of the amount of TYLCSV

in the first leaf below the apex was obtained. The kinetics of virus retention within different batches of viruliferous whiteflies was also analysed. The real-time PCR was 2200-fold more sensitive than membrane hybridisation, allowing detection of as few as 10 viral copies in a sample. These methods are potentially suitable for several applications, such as plant breeding for resistance, analysis of virus replication, and virus-vector interaction studies. (c) 2007 Elsevier B.V. All rights reserved.”
“A male infant weighing 3400 g was born at 37 weeks’ gestation after an uncomplicated pregnancy. The mother is a 24-year-old primipara who has type A Rh-positive blood. The infant’s course in the hospital nursery was uncomplicated. Although his mother needed considerable help in establishing effective breast-feeding, he was exclusively breast-fed. Jaundice was noted at the age of 34 hours. The total serum bilirubin level

was 7.5 mg per deciliter (128 mu mol per liter). The infant was discharged at the age of 40 hours and is seen in the pediatrician’s office 2 days later, now with marked jaundice. The results of his physical examination are otherwise normal, but his weight, at 3020 g, is Poziotinib mw 11% below his birth weight. His total serum bilirubin level is 19.5 mg per deciliter (333 mu mol per liter), and his conjugated (direct) bilirubin level 0.6 mg per Entinostat datasheet deciliter (10 mu mol per liter). The complete blood count and peripheral-blood smear are normal. The infant has

type A Rh-positive blood. The pediatrician consults a neonatologist regarding the need for phototherapy.”
“The recently released Linear Array (R) human papillomavirus (HPV) genotyping test (Roche Diagnostics) provides a standardized method for simultaneous detection of up to 37 individual HPV types. This test offers a rapid approach for detecting and longitudinal monitoring of patients infected with high-risk (HR) HPV. However, it cannot rule out HPV52 infections in the presence of carcinogenic HPV genotypes 33, 35 and/or 58. As such, often only a non-definitive result of HPV52 presence can be reported. This study describes the development of a real-time PCR assay using an HPV52-specific hydrolysis probe in conjunction with the newly released Roche LightCycler (R) 480 system. HPV52 was readily detected among DNA extracts from samples previously identified with possible HPV52 by the linear array test. Specificity was analyzed using a panel of DNA extracts previously identified as containing single/multiple HPV types, with or without HPV52.

This result exemplifies in the case of CRP the capability of our

This result exemplifies in the case of CRP the capability of our computational tool to predict effective binding sites for UO22+ in proteins and is a first evidence of calcium substitution by the uranyl cation in a native protein.”
“Purpose: We prospectively evaluated the efficacy JIB04 molecular weight of dextranomer/hyaluronic acid based implants for the endoscopic treatment of neurogenic urinary incontinence.

Materials and Methods: We prospectively studied patients undergoing endoscopic injection of dextranomer/hyaluronic acid for structural incontinence beginning in October 1997.

Preoperative evaluation consisted of medical history, incontinence charts, urine culture, urinary tract ultrasound and videourodynamics, which were repeated regularly during followup. At each check details evaluation patients were classified as cured or significantly improved (treatment success), or not significantly improved (treatment failure). Followup ranged from 1 to 13 years (mean 7.4).

Results:

A total of 48 patients 5 to 20 years old with congenital (45 patients) or acquired (3) neurogenic bladder suffering from severe sphincteric incompetence were included. Of the patients 30 underwent 1, 13 underwent 2 and 5 underwent 3 treatment sessions. Mean injected volume was 4.6 ml per session. Five patients had previously undergone bladder neck surgery. Two patients lost to followup in the Selleckchem SHP099 short term were classified as treatment failures. Of the patients 45 had more than 2 years of followup, of whom 19 (39.6%) were dry, 6 (12.5%) were significantly improved

and 23 (47.9%) had no significant improvement observed. Female patients achieved a significantly higher success rate than males (p = 0.05). No significant clinical or urodynamic criterion was predictive of success or failure. Posttreatment bladder deterioration developed in 10 cases (7 successes and 3 failures), which were managed by bladder augmentation.

Conclusions: Endoscopic treatment of neurogenic urinary sphincter insufficiency with dextranomer/hyaluronic acid is effective in half of the patients. Recurrence of incontinence after 1 year is mainly a sign of bladder deterioration.”
“Vestibulo-ocular reflexes are the fastest compensatory reflex systems. One of these is the translational vestibulo-ocular reflex (TVOR) which stabilizes the gaze at a given fixation point during whole body translations. For a proper response of the TVOR the eyes have to counter rotate in the head with a velocity that is inversely scaled to viewing distance of the target. It is generally assumed that scaling of the TVOR is automatically coupled to vergence angle at the brainstem level. However, different lines of evidence also argue that in humans scaling of the TVOR also depends on a mechanism that pre-sets gain on a priori knowledge of target distance.

Interestingly, the conserved sequences are located within the reg

Interestingly, the conserved sequences are located within the regions identified as important for efficient packaging. By utilizing influenza virus reverse genetics, we have

rescued mutant viruses containing synonymous mutations within these highly conserved regions. Packaging of viral RNAs check details in these viruses was analyzed by reverse transcription using a universal primer and quantitative PCR for individual segments. Employing this approach, we have identified regions in the polymerase gene segments that, if mutated, result in reductions of more than 90% in the packaging of that particular polymerase viral RNA. Reductions in the level of packaging of a polymerase viral RNA frequently resulted in reductions of other viral RNAs as well, and the results form a pattern of hierarchy of segment interactions. This work provides further evidence for a selective packaging mechanism for influenza A viruses, demonstrating that these highly conserved regions are important

for efficient C59 wnt datasheet packaging.”
“Fifteen years after its resurrection, pallidotomy for Parkinson’s disease (PD) and dystonia has once again been supplanted, this time by deep brain stimulation (DBS). Did this occur because pallidotomy was not effective or safe, or because DBS was found to be more effective and safer? This review focuses on the evidence-and its quality-supporting the effectiveness and safety of pallidotomy SU5402 for PD and dystonia, and the comparative

effectiveness and safety of DBS of the subthalamic nucleus (STN) and globus pallidus pars interna (GPi). Discussed first are the determinants of “”level 1″” recommendations, including the confounding effects on interpretation of randomized clinical trials (RCTs) that fail to control for patient bias (i.e., placebo effects). Although several RCTs have been performed comparing unilateral pallidotomy to medical therapy, GPi DBS, or STN DBS for PD, none controlled for patient bias. Comparison of these trials to estimate the placebo effect, and examination of retrospective case series, suggests that the true effectiveness of unilateral pallidotomy is 20% to 30% reduction of ‘off’ total motor UPDRS scores, which is similar to the effects of unilateral GPi DBS or STN DBS, but less than bilateral STN DBS. At experienced centers, safety of unilateral pallidotomy appears equivalent to unilateral DBS, but bilateral DBS is likely safer than bilateral pallidotomy. Whereas there have been no RCTs of pallidotomy for dystonia, two double-blind, sham-controlled RCTs of bilateral GPi DBS were performed. Nevertheless, limited uncontrolled series Suggest that bilateral pallidotomy is similar to GPi DBS in effectiveness and safety for dystonia. Thus, pallidotomy was not rejected because of lack of effectiveness or safety, and it remains a viable alternative in situations where DBS is not available or not feasible.

M , Gitelman, D , Simmons, K , Bloise, S M , Parrish, T , & Mesu

M., Gitelman, D., Simmons, K., Bloise, S. M., Parrish, T., & Mesulam, M. M. (2005). Monetary incentives enhance processing in brain regions mediating top-down control of attention. Cerebral Cortex, 15(12), 1855-1865]. Both groups were able to use Spatial Cues to generate an anticipatory attentional shift towards the cued location. The prospect of winning (but JSH-23 datasheet not losing) money enhanced attentional shifts in EC Subjects, all effect that was mediated by OFC activation. In contrast, only the prospect of losing money enhanced attentional

shifts in MCI subjects, an effect that correlated with PCC activation. Behavioral effects of incentive upon spatial attention are only partially maintained in EC and MCI with corresponding modifications in the underlying neural circuitry. These results suggest a reorganization of the relationships between the limbic system and spatial attention network in healthy aging and MCI. (C) 2008 Elsevier Ltd. All rights reserved.”
“Objectives. The present

study examines gender differences in changes in functional status after age 50 and how such differences vary across different age groups.

Methods. Data came from the Health and Retirement Study, involving up to six repeated observations of a national sample of Americans older than 50 years of age between find more 1995 and 2006. We employed hierarchical linear models with time-varying covariates in depicting temporal variations

in functional status between men and women.

Results. As a quadratic function, the worsening of functional status was more accelerated in terms of the intercept and rate of change among women and those in older age groups. In addition, gender differences in the level Of functional impairment were more substantial in older persons than in younger individuals, although differences in the rate of change between men and women remained constant across age groups.

Discussion. A life course perspective can lead to new insights regarding gender variations in health within the context of intrapersonal and interpersonal differences. Smaller gender differences www.selleck.cn/products/vx-661.html in the level of functional impairment in the younger groups may reflect improvement of women’s socioeconomic status. I greater rate of increase in chronic diseases among men, and less debilitating effects of diseases.”
“Repeat offenders are commonly given more severe sentences than first-time offenders for the same violations. Though this practice makes intuitive sense, the theory behind escalating penalties is disputed in both legal and economic theories. Here we investigate folk intuitions concerning the moral and intentional status of actions performed by people with positive versus negative prior records. We hypothesized that prior record Would modulate both moral judgment and mental state reasoning.