Rotaviruses of group A (RVA) are enteric pathogens with well documented zoonotic transmissions to humans. The segmented genome of the virus enables reassortment events which might alter host susceptibility and/or disease course. Genetic analysis of rotavirus in dogs so far only revealed RVAs with the VP7 and VP4 genome constellation G3P. RVA G3P have also been found in cats, humans, monkeys and bats. In the present study an unusual RVA of genotype G8P is described which was isolated from an asymptomatically infected young dog. The dog did not show signs of diarrhoea. Analysis of full length segments of VP2, VP6 and VP7 as well as NSP1 to NSP5 revealed a typical bovine-like genotype constellation G8-P-I2-Rx-C2-Mx-A3-N2-T6-E2-H3. Phylogenetic analysis supports the hypothesis of an interspecies transmission from a bovine/artiodactyl species or from humans to the young dog. The isolate is likely to represent a multiple reassortant virus.
Chromosome 22q11.2 deletion syndrome (22q11DS) confers 25% risk for psychosis and is an invaluable window for understanding the neurobiological substrate of psychosis risk. The Structured Interview for Prodromal Syndromes (SIPS) is well validated in nondeleted populations for detecting clinical risk but has only recently been applied to 22q11DS. We assessed the largest 22q11DS cohort to date and report on SIPS implementation and symptoms elicited.
Modern optical sensors and measurement systems usually are a powerful combination of optical elements, active hardware components like actuators or sensing devices as well as a sophisticated control software and data evaluation algorithms. In order to develop and operate such systems, it is necessary to have a flexible, intuitive, and fast underlying software framework that also allows for rapid prototyping of a sensor in a dynamic lab environment. This software must be able to control and communicate with all necessary hardware devices and has to provide all the highly performant evaluation, data, and image processing algorithms required. In this publication, we want to present the open source measurement and data evaluation software suite itom, which has been designed considering the denoted requirements and whose development began in 2011.
Studies examining the processing of threat-related information in schizophrenia suggest that patients may show intact abilities to detect nonsocial threats despite impaired processing of social threat. The present study examined potential differences between social and nonsocial threat detection abilities in schizophrenia via two analogous threat perception tasks: one that used nonsocial threat (i.e., snakes) and one that used social threat (i.e., angry faces). Both tasks have reliably demonstrated a threat superiority effect (TSE) among healthy individuals in which threat-related stimuli are detected more accurately and efficiently than non-threat-related stimuli. Results from 30 healthy controls and 35 individuals with schizophrenia indicated that control participants showed a normative TSE on both the nonsocial and social tasks. In contrast, patients showed a TSE on only the nonsocial task, demonstrating intact detection abilities for nonsocial threat but impaired detection of social threats. The discrepant performance across nonsocial and social threat detection tasks within the patient group is consistent with evidence indicating that social and nonsocial information processing can be differentially affected in schizophrenia.
The prevalence of extended-spectrum beta-lactamase (ESBL)-positive Klebsiella pneumoniae is growing worldwide. Infections with these bacteria are suspected to be related to increased mortality. We aimed to estimate the distribution of ESBL genotypes and to assess the impact on mortality associated with ESBL positivity in cases of bloodstream infection (BSI) due to K. pneumoniae. We performed a cohort study on patients with K. pneumoniae BSI between 2008 and 2011. Presence of ESBL genes was analyzed by PCR and sequencing. Risk factors for mortality were analyzed by Cox-proportional hazard regression. We identified 286 ESBL-negative (81%) and 66 (19%) ESBL-positive cases. 97% (n = 64) of the ESBL-positive isolates were susceptible for meropenem. The most common ESBL genotypes were CTX-M-15 (60%), SHV-5 (27%) and CTX-M-3 (5%). Significant risk factors for mortality were chronic pulmonary disease (HR 1.747) and moderate/severe renal disease (HR 2.572). ESBL positivity was not associated with increased mortality.
Over the past 2 decades, increased efforts have focused on identifying those at genetic or clinical risk for psychosis and promoting interventions that may alter the onset or trajectory of schizophrenia. We review studies published between 2010-2013 that: (1) investigate at-risk states for psychosis in larger epidemiological studies; (2) identify causes of certain clinical presentations of the schizophrenia phenotype and (3) investigate focused and multidisciplinary approaches to treat early clinical symptoms. The article places these recent studies within the context of prior research and the concept of potential measures to prevent or ameliorate the onset of psychosis.
Altered facial expressions of emotions are characteristic impairments in schizophrenia. Ratings of affect have traditionally been limited to clinical rating scales and facial muscle movement analysis, which require extensive training and have limitations based on methodology and ecological validity. To improve reliable assessment of dynamic facial expression changes, we have developed automated measurements of facial emotion expressions based on information-theoretic measures of expressivity of ambiguity and distinctiveness of facial expressions. These measures were examined in matched groups of persons with schizophrenia (n = 28) and healthy controls (n = 26) who underwent video acquisition to assess expressivity of basic emotions (happiness, sadness, anger, fear, and disgust) in evoked conditions. Persons with schizophrenia scored higher on ambiguity, the measure of conditional entropy within the expression of a single emotion, and they scored lower on distinctiveness, the measure of mutual information across expressions of different emotions. The automated measures compared favorably with observer-based ratings. This method can be applied for delineating dynamic emotional expressivity in healthy and clinical populations.
Patients with borderline personality disorder (BPD) suffer from various impairments in emotional functioning such as affective instability, inappropriate anger and unstable relationships. These deficits may influence two fundamental motivational systems, the behavioral inhibition system (BIS) and behavioral activation system (BAS). To investigate behavioral intentions and possible impairments in BPD we applied an implicit joystick task to measure implicit behavioral tendencies in response to facial expressions (happiness, sadness, anger, fear and neutral) in 25 patients with BPD and matched 25 healthy controls (HC). Additionally, we evaluated explicit approach and avoidance reactions to these social stimuli, emotion recognition abilities and subjective behavioral ratings. Our data analysis suggests that, although BPD patients accurately identified facial emotional expressions and reacted to them similarly as HC in the joystick task, they had significantly stronger avoidance tendencies in the rating task, especially for happiness and fear. On top of this they exhibited increased BIS sensitivity and decreased BAS sensitivity in the self-report measures. Possible influences are maladaptive cognitive schemas, high negative affect, insecure attachment style and a negative evaluation bias. The observed dysfunctional avoidance ratings may influence the appraisal of socially relevant stimuli and therefore adds further knowledge on social interaction problems in BPD.
Uropathogenic Escherichia coli (UPEC) is the most common cause of community- and hospital-acquired urinary tract infections (UTIs). Isolates from uncomplicated community-acquired UTIs express a variety of virulence traits that promote the efficient colonization of the urinary tract. In contrast, nosocomial UTIs can be caused by E. coli strains that differ in their virulence traits from the community-acquired UTI isolates. UPEC virulence markers are used to distinguish these facultative extraintestinal pathogens, which belong to the intestinal flora of many healthy individuals, from intestinal pathogenic E. coli (IPEC). IPEC is a diarrheagenic pathogen with a characteristic virulence gene set that is absent in UPEC. Here, we characterized 265 isolates from patients with UTIs during inpatient or outpatient treatment at a hospital regarding their phylogenies and IPEC or UPEC virulence traits. Interestingly, 28 of these isolates (10.6%) carried typical IPEC virulence genes that are characteristic of enteroaggregative E. coli (EAEC), Shiga toxin-producing E. coli (STEC), and atypical enteropathogenic E. coli (aEPEC), although IPEC is not considered a uropathogen. Twenty-three isolates harbored the astA gene coding for the EAEC heat-stable enterotoxin 1 (EAST1), and most of them carried virulence genes that are characteristic of UPEC and/or EAEC. Our results indicate that UPEC isolates from hospital patients differ from archetypal community-acquired isolates from uncomplicated UTIs by their spectrum of virulence traits. They represent a diverse group, including EAEC, as well as other IPEC pathotypes, which in addition contain typical UPEC virulence genes. The combination of typical extraintestinal pathogenic E. coli (ExPEC) and IPEC virulence determinants in some isolates demonstrates the marked genome plasticity of E. coli and calls for a reevaluation of the strict pathotype classification of EAEC.
A large body of literature has documented facial emotion perception impairments in schizophrenia. More recently, emotion perception has been investigated in persons at genetic and clinical high-risk for psychosis. This study compared emotion perception abilities in groups of young persons with schizophrenia, clinical high-risk, genetic risk and healthy controls. Groups, ages 13-25, included 24 persons at clinical high-risk, 52 first-degree relatives at genetic risk, 91 persons with schizophrenia and 90 low risk persons who completed computerized testing of emotion recognition and differentiation. Groups differed by overall emotion recognition abilities and recognition of happy, sad, anger and fear expressions. Pairwise comparisons revealed comparable impairments in recognition of happy, angry, and fearful expressions for persons at clinical high-risk and schizophrenia, while genetic risk participants were less impaired, showing reduced recognition of fearful expressions. Groups also differed for differentiation of happy and sad expressions, but differences were mainly between schizophrenia and control groups. Emotion perception impairments are observable in young persons at-risk for psychosis. Preliminary results with clinical high-risk participants, when considered along findings in genetic risk relatives, suggest social cognition abilities to reflect pathophysiological processes involved in risk of schizophrenia.
The genetic hallmark of Burkitt lymphoma (BL) is the t(8;14)(q24;q32) and its variants leading to activation of the MYC oncogene. It is a matter of debate whether true BL without MYC translocation exists. Here, we identified 59 lymphomas concordantly called BL by 2 gene expression classifiers among 753 B-cell lymphomas. Only 2 (3%) of these 59 molecular BL lacked a MYC translocation, which both shared a peculiar pattern of chromosome 11q aberration characterized by interstitial gains including 11q23.2-q23.3 and telomeric losses of 11q24.1-qter. We extended our analysis to 17 MYC-negative high-grade B-cell lymphomas with a similar 11q aberration and showed this aberration to be recurrently associated with morphologic and clinical features of BL. The minimal region of gain was defined by high-level amplifications in 11q23.3 and associated with overexpression of genes including PAFAH1B2 on a transcriptional and protein level. The recurrent region of loss contained a focal homozygous deletion in 11q24.2-q24.3 including the ETS1 gene, which was shown to be mutated in 4 of 16 investigated cases. These findings indicate the existence of a molecularly distinct subset of B-cell lymphomas reminiscent of BL, which is characterized by deregulation of genes in 11q.
Gender dysphoria (also known as "transsexualism") is characterized as a discrepancy between anatomical sex and gender identity. Research points towards neurobiological influences. Due to the sexually dimorphic characteristics of the human voice, voice gender perception provides a biologically relevant function, e.g. in the context of mating selection. There is evidence for a better recognition of voices of the opposite sex and a differentiation of the sexes in its underlying functional cerebral correlates, namely the prefrontal and middle temporal areas. This fMRI study investigated the neural correlates of voice gender perception in 32 male-to-female gender dysphoric individuals (MtFs) compared to 20 non-gender dysphoric men and 19 non-gender dysphoric women. Participants indicated the sex of 240 voice stimuli modified in semitone steps in the direction to the other gender. Compared to men and women, MtFs showed differences in a neural network including the medial prefrontal gyrus, the insula, and the precuneus when responding to male vs. female voices. With increased voice morphing men recruited more prefrontal areas compared to women and MtFs, while MtFs revealed a pattern more similar to women. On a behavioral and neuronal level, our results support the feeling of MtFs reporting they cannot identify with their assigned sex.
The rate of infections due to extended-spectrum ?-lactamase (ESBL)-producing Escherichia coli is growing worldwide. These infections are suspected to be related to increased mortality. We aimed to estimate the difference in mortality due to bloodstream infections (BSIs) with ESBL-positive and ESBL-negative E. coli isolates and to determine the molecular epidemiology of our ESBL-positive isolates.
Chromosomal translocations affecting the MYC oncogene are the biologic hallmark of Burkitt lymphomas but also occur in a subset of other mature B-cell lymphomas. If accompanied by a chromosomal break targeting the BCL2 and/or BCL6 oncogene these MYC translocation positive (MYC+) lymphomas are called double-hit lymphomas, otherwise the term single-hit lymphomas is applied. In order to characterize the biologic features of these MYC+ lymphomas other than Burkitt lymphoma we explored, after exclusion of molecular Burkitt lymphoma as defined by gene expression profiling, the molecular, pathological and clinical aspects of 80 MYC-translocation positive lymphomas (31 single-hit, 46 double-hit & 3 MYC+-lymphomas with unknown BCL6 status). Comparison of single-hit and double-hit lymphomas revealed no difference in MYC partner (IG/non-IG), genomic complexity, MYC expression or gene expression profile. Double-hit lymphomas showed more frequent GCB-like gene expression profile and higher IGH and MYC mutation frequencies. Gene expression profiling revealed 130 differentially expressed genes between BCL6+/MYC+ and BCL2+/MYC+ double-hit lymphomas. BCL2+/MYC+ double-hit lymphomas showed a more frequent GCB-like gene expression profile. Analysis of all lymphomas according to MYC partner (IG/non-IG) revealed no substantial differences. In this series of lymphomas, in which immunochemotherapy was administered in only a minority of cases, single-hit and double-hit lymphomas had a similar poor outcome in contrast with molecular Burkitt lymphoma and lymphomas without MYC break. Our data suggest that, after excluding molecular Burkitt lymphoma and pediatric cases, MYC+ lymphomas are biologically quite homogenous with single-hit and double-hit lymphomas as well as IG-MYC and non-IG-MYC+ lymphomas sharing various molecular characteristics.
Background:Previous research has provided compelling support for olfactory dysfunction in schizophrenia patients, their first-degree relatives, and youth at-risk for psychosis. A previous meta-analysis revealed large effect sizes across olfactory tasks but was limited to 2 olfactory tasks and did not examine moderator variables. Thus, the current meta-analysis was undertaken to incorporate additional studies, risk cohorts, olfactory test domains, and moderator variable analyses.Method:A meta-analysis was conducted on 67 publications examining olfactory function in schizophrenia patients and 15 publications examining olfactory functioning in youth at-risk for psychosis, first-degree relatives of schizophrenia patients, and individuals with schizotypy.Results:Results revealed medium-to-large olfactory deficits in schizophrenia patients though significant heterogeneity was evident. Several variables moderated overall study effects. At-risk youths similarly demonstrated medium-to-large effect sizes, whereas first-degree relatives and individuals with schizotypy showed small effects.Conclusions:Findings suggest robust olfactory deficits in schizophrenia and at-risk youths. In schizophrenia, several variables had significant impact on these deficits and warrant consideration in prospective studies. Our findings also indicate that olfactory measures may be a useful marker of schizophrenia risk status.
The basis for different neural activations in response to male and female voices as well as the question, whether men and women perceive male and female voices differently, has not been thoroughly investigated. Therefore, the aim of the present study was to examine the behavioral and neural correlates of gender-related voice perception in healthy male and female volunteers. fMRI data were collected while 39 participants (19 female) were asked to indicate the gender of 240 voice stimuli. These stimuli included recordings of 3-syllable nouns as well as the same recordings pitch-shifted in 2, 4 and 6 semitone steps in the direction of the other gender. Data analysis revealed a) equal voice discrimination sensitivity in men and women but better performance in the categorization of opposite-sex stimuli at least in men, b) increased responses to increasing gender ambiguity in the mid cingulate cortex and bilateral inferior frontal gyri, and c) stronger activation in a fronto-temporal neural network in response to voices of the opposite sex. Our results indicate a gender specific processing for male and female voices on a behavioral and neuronal level. We suggest that our results reflect higher sensitivity probably due to the evolutionary relevance of voice perception in mate selection.
Pharmaceuticals are normally barely removed by conventional wastewater treatments. Advanced technologies as a post-treatment, could prevent these pollutants reaching the environment and could be included in a centralized treatment plant or, alternatively, at the primary point source, e.g. hospitals. In this study, the environmental impacts of different options, as a function of several advanced treatments as well as the centralized/decentralized implementation options, have been evaluated using Life Cycle Assessment (LCA) methodology. In previous publications, the characterization of the toxicity of pharmaceuticals within LCA suffers from high uncertainties. In our study, LCA was therefore only used to quantify the generated impacts (electricity, chemicals, etc.) of different treatment scenarios. These impacts are then weighted by the average removal rate of pharmaceuticals using a new Eco-efficiency Indicator EFI. This new way of comparing the scenarios shows significant advantages of upgrading a centralized plant with ozonation as the post-treatment. The decentralized treatment option reveals no significant improvement on the avoided environmental impact, due to the comparatively small pollutant load coming from the hospital and the uncertainties in the average removal of the decentralized scenarios. When comparing the post-treatment technologies, UV radiation has a lower performance than both ozonation and activated carbon adsorption.
Given the presence of odor identification impairment in individuals with schizophrenia and recent evidence of aberrant odor hedonic processing, the aim of this investigation was to examine the influence of valence and intensity on odor identification in schizophrenia patients, their first-degree family members, and young persons at clinical risk for psychosis. Participants completed the 16-item Sniffin Stick Odor Identification Test. A logistic regression was conducted to assess the influence of valence and intensity on odor identification accuracy. Identification performance in the schizophrenia patients and youths at clinical risk for psychosis was significantly influenced by odor valence, but not intensity. Identification accuracy in first-degree family members was not influenced by valence or intensity. These data suggest that abnormalities in odor valence perception may represent an environmentally-mediated marker for hedonic disturbance that could have predictive utility in future conversion to psychosis. Further research examining the utility of odor valence measures as markers for psychosis risk is warranted.
Similar to adults with schizophrenia, youth at high risk for developing schizophrenia present difficulties in recognizing emotions in faces. These difficulties might index vulnerability for schizophrenia and play a role in the development of the illness. Facial emotion recognition (FER) impairments have been implicated in declining social functioning during the prodromal phase of illness and are thus a potential target for early intervention efforts. This study examined 9- to 14-year-old children: 34 children who presented a triad of well-replicated antecedents of schizophrenia (ASz), including motor and/or speech delays, clinically relevant internalizing and/or externalizing problems, and psychotic-like experiences (PLEs), and 34 typically developing (TD) children who presented none of these antecedents. An established FER task (ER40) was used to assess correct recognition of happy, sad, angry, fearful, and neutral expressions, and facial emotion misperception responses were made for each emotion type. Relative to TD children, ASz children presented an overall impairment in FER. Further, ASz children misattributed neutral expressions to face displaying other emotions and also more often mislabeled a neutral expression as sad compared with healthy peers. The inability to accurately discriminate subtle differences in facial emotion and the misinterpretation of neutral expressions as sad may contribute to the initiation and/or persistence of PLEs. Interventions that are effective in teaching adults to recognize emotions in faces could potentially benefit children presenting with antecedents of schizophrenia.
Suppressor of cytokine signaling 1 (SOCS1) is frequently mutated in primary mediastinal and diffuse large B-cell lymphomas (DLBCL). Currently, the prognostic relevance of these mutations in DLBCL is unknown. To evaluate the value of the SOCS1 mutation status as a prognostic biomarker in DLBCL patients, we performed full-length SOCS1 sequencing in tumors of 154 comprehensively characterized DLBCL patients. We identified 90 SOCS1 mutations in 16% of lymphomas. With respect to molecular consequences of mutations, we defined two distinct subtypes: those with truncating (major) and those with non-truncating mutations (minor), respectively. The SOCS1 mutated subgroup or the minor/major subtypes cannot be predicted on clinical grounds; however, assignment of four established gene-expression profile-based classifiers revealed significant associations of SOCS1 major cases with germinal center and specific pathway activation pattern signatures. Above all, SOCS1 major cases have an excellent overall survival, even better than the GCB-like subgroup. SOCS1 minor cases had a dismal survival, even worse than the ABC gene signature group. The SOCS1 mutation subsets retained prognostic significance in uni- and multivariate analyses. Together our data indicate that assessment of the SOCS1 mutation status is a single gene prognostic biomarker in DLBCL.
Asymptomatic bacteriuria (ABU) is a condition where bacteria stably colonize the urinary tract, in a manner closely resembling commensalism at other mucosal sites. The patients carry >10(5) CFU/ml for extended periods of time and rarely develop symptoms. Contrasting the properties of ABU strains to those of uropathogenic isolates causing symptomatic infection is therefore highly relevant to understand mechanisms of bacterial adaptation. The prototype ABU strain Escherichia coli 83972 has a smaller genome than uropathogenic E. coli (UPEC) strains with deletions or point mutations in several virulence genes, suggesting that ABU strains undergo a programmed reductive evolution within human hosts. This study addressed if these observations can be generalized. Strains causing ABU in outpatients or hospitalized patients after catheterization or other invasive procedures were compared to commensal E. coli isolates from the intestinal flora of healthy individuals. Notably, clonal complex 73 (CC73) was a prominent phylogenetic lineage dominated by ABU isolates. ABU isolates from outpatients and hospitalized patients had a similar overall virulence gene repertoire, which distinguished them from many commensals, but typical UPEC virulence genes were less frequently attenuated in hospital strains than in outpatient strains or commensals. The decreased virulence potential of outpatient ABU isolates relative to that of ABU strains from hospitalized patients supports the hypothesis that loss of expression or decay of virulence genes facilitates long-term carriage and adaptation to host environments.
Abstract Objectives. While deficits in odor identification and discrimination have been reported in schizophrenia, few studies have examined the relative specificity of these deficits in patients and at-risk youth. Method. Sniffin Sticks odor identification and discrimination were assessed in schizophrenia outpatients and non-ill first-degree relatives (Study One), as well as youth at clinical (CR) or genetic (GR) risk for schizophrenia (Study Two). Scores were z-transformed, using the performance of a demographically-matched adult or adolescent comparison group. Results. Patients and relatives were impaired on odor identification, but odor discrimination impairment was limited to the patient group. A similar pattern of impairment emerged in at-risk youth. GR youth were impaired on odor identification but not discrimination, while CR youth were impaired on both tasks. In patients, olfactory impairment was correlated with negative symptomatology. Conclusions. To our knowledge, this is the first study to show that CR youth are impaired on both olfactory tasks, as observed in adult schizophrenia patients. GR youth were impaired only on odor identification like their adult counterparts. These data suggest that odor identification impairment, in isolation, may represent a genetic marker of vulnerability for schizophrenia, while odor discrimination deficits may be a biomarker associated with the development of psychosis.
Escherichia coli (E. coli) exhibits considerable physiological and metabolic versatility and includes a variety of non-pathogenic, commensal variants, which belong to the normal gut flora of humans and warm-blooded animals. Additionally, several pathogenic variants have been identified which cause various types of intestinal or extraintestinal infections in humans and animals. In contrast to intestinal pathogenic E. coli (IPEC), which are obligate pathogens, extraintestinal pathogenic E. coli (ExPEC) are facultative pathogens which belong to the normal gut flora of a certain fraction of the healthy population where they live as commensals. Comparative genomics and epidemiological studies have been applied to study genomic diversity, markers, and phenotypic traits that may support discrimination of different E. coli pathotypes. Whereas IPEC are often epidemiologically and phylogenetically distinct from ExPEC and non-pathogenic, commensal strains, many ExPEC and non-pathogenic E. coli share large genomic fractions. Furthermore, extraintestinal infections of elderly or immunocompromised patients can be caused by E. coli variants which differ in their geno- and phenotypes from archetypal ExPEC. Thus, strain typing based on the detection of a limited number of ExPEC virulence/fitness-related genes may be ambiguous. A limited number of ExPEC-dominated clonal complexes can be identified in the E. coli population by multi locus sequence typing. Nevertheless, ExPEC and non-pathogenic E. coli cannot be clearly discriminated by molecular epidemiological approaches. Increased knowledge of the phylogeny, virulence and fitness traits, and host factors contributing to host susceptibility of the different groups of ExPEC variants is required for a better understanding of the biological basis of ExPEC infections.
Adults with 22q11.2 Deletion syndrome (22q11DS) have increased prevalence of schizophrenia features. Our goal is to compare the neurocognitive profile in 22q11DS, schizophrenia and individuals at risk for schizophrenia. Twenty-one 22q11DS patients (8-32 years, mean 14.9 years, 15M, 6F) were matched to four comparison groups on age: low risk (n?=?21), first-degree family members of schizophrenia patients (genetic risk, n?=?20), individuals exhibiting putatively prodromal symptoms (clinical risk, n?=?19), and patients with schizophrenia (n?=?21). All participants received semi-structured interviews [Diagnostic Interview for Genetic Studies (DIGS) and the Structured Interview for Prodromal Syndromes (SIPS)], and a computerized neurocognitive battery (CNB) measuring the following domains: Abstraction and Mental Flexibility, Attention, Working Memory, Verbal Memory, Face Memory, Spatial Memory, Language, Spatial Processing, Sensorimotor Dexterity, and Emotion Processing. Sixty percent of 22q11DS participants met SIPS criteria for prodromal symptoms and one participant met criteria for paranoid schizophrenia. Thirty-eight percent met criteria for Depressive Disorders. All 22q11DS participants successfully completed the CNB. 22q11DS participants were significantly less accurate in nearly all domains, but had similar speed of response compared to the other groups. Their profile resembled that of the psychosis groups in accuracy and speed, except for more pronounced deficits in accuracy for face memory and emotion processing. Subthreshold psychotic symptoms are present in a high proportion of 22q11DS participants. Deficits shown in the CNB are more pronounced for accuracy than speed relative to the psychosis groups with similar profiles. Similar deficits have been described in the 22q11DS population using non-computerized measures, which require increased testing time.
There is increasing evidence that schizophrenia patients have difficulties in the hedonic appraisal of odors. In a prior study, we assessed olfactory hedonic perception birhinally and found that males with schizophrenia failed to attach the appropriate hedonic valence to a pleasant odor, despite correctly perceiving changes in odor intensity. Female patients, in contrast, exhibited normal responses. The current study extends this work by examining odor valence processing in unaffected first-degree relatives of schizophrenia patients, to determine the extent to which this abnormality may be genetically mediated. We also examine odor valence processing unirhinally, rather than birhinally, to probe possible lateralized differences in patients hedonic processing deficits.
The cylindromatosis gene (CYLD) was identified as a tumor suppressor gene, which is mutated in familial cylindromatosis (Brooke-Spiegler syndrome), an autosomal-dominant predisposition to multiple tumors of the skin appendages. CYLD is a deubiquitinating enzyme acting as a negative regulator of the nuclear factor ?B (NF-?B) signaling pathway by removing lysine-63-linked polyubiquitin chains from NF-?B activating proteins. In order to investigate the role of CYLD in apoptotic signaling in human hepatocellular carcinoma (HCC) cells, we first studied the expression levels of CYLD in HCC tissues. CYLD expression was lower in HCC both at protein and mRNA levels compared to the surrounding non-malignant tissue. In order to further study the role of CYLD in the apoptotic sensitivity of HCC cells, CYLD was specifically down-regulated in HCC cell lines via RNA interference. The specific down-regulation of CYLD resulted in increased resistance towards treatment with doxorubicin, 5-fluorouracil and cisplatin. In addition, the down-regulation of CYLD in HCC cells decreased the sensitivity towards tumor necrosis factor-?-induced apoptosis. The CYLD knockdown also led to the degradation of the NF-?B inhibitor, I?B-?, resulting in enhanced NF-?B activity in HCC cells. Finally, we found that CYLD expression was triggered by the multikinase inhibitor, sorafenib, by the inhibition of Raf-1, as well as by the blockage of the pro-survival kinases, MEK (U0126) and the epidermal growth factor receptor (AG1478). In summary, we show that CYLD is down-regulated in human HCC and is involved in the apoptotic resistance of HCC cells. Our data identify the reconstitution of CYLD expression as an attractive approach for overcoming resistance to treatment in HCC.
The extracytoplasmic function sigma factor ?(T) is the master regulator of general stress response in Caulobacter crescentus and controls the expression of its paralogue ?(U). In this work we showed that PhyR and NepR act, respectively, as positive and negative regulators of ?(T) expression and function. Biochemical data also demonstrated that NepR directly binds ?(T) and the phosphorylated form of PhyR. We also described the essential role of the histidine kinase gene CC3474, here denominated phyK, for expression of ?(T)-dependent genes and for resistance to stress conditions. Additionally, in vivo evidence of PhyK-dependent phosphorylation of PhyR is presented. This study also identified a conserved cysteine residue (C95) located in the periplasmic portion of PhyK that is crucial for the function of the protein. Furthermore, we showed that PhyK, PhyR and ?(T) regulate the same set of genes and that ?(T) apparently directly controls most of its regulon. In contrast, ?(U) seems to have a very modest contribution to the expression of a subset of ?(T)-dependent genes. In conclusion, this report describes the molecular mechanism involved in the control of general stress response in C. crescentus.
The prognosis of germinal center-derived B-cell (GCB) lymphomas, including follicular lymphoma and diffuse large-B-cell lymphoma (DLBCL), strongly depends on age. Children have a more favorable outcome than adults. It is not known whether this is because of differences in host characteristics, treatment protocols, or tumor biology, including the presence of chromosomal alterations. By screening for novel IGH translocation partners in pediatric and adult lymphomas, we identified chromosomal translocations juxtaposing the IRF4 oncogene next to one of the immunoglobulin (IG) loci as a novel recurrent aberration in mature B-cell lymphoma. FISH revealed 20 of 427 lymphomas to carry an IG/IRF4-fusion. Those were predominantly GCB-type DLBCL or follicular lymphoma grade 3, shared strong expression of IRF4/MUM1 and BCL6, and lacked PRDM1/BLIMP1 expression and t(14;18)/BCL2 breaks. BCL6 aberrations were common. The gene expression profile of IG/IRF4-positive lymphomas differed from other subtypes of DLBCL. A classifier for IG/IRF4 positivity containing 27 genes allowed accurate prediction. IG/IRF4 positivity was associated with young age and a favorable outcome. Our results suggest IRF4 translocations to be primary alterations in a molecularly defined subset of GCB-derived lymphomas. The probability for this subtype of lymphoma significantly decreases with age, suggesting that diversity in tumor biology might contribute to the age-dependent differences in prognosis of lymphoma.
Mesoderm development (MESD) is a 224 amino acid mouse protein that acts as a molecular chaperone for the low-density lipoprotein receptor (LDLR) family. Here, we provide evidence that the region 45-184 of MESD is essential and sufficient for this function and suggest a model for its mode of action. NMR studies reveal a ?-?-?-?-?-? core domain with an ?-helical N-terminal extension that interacts with the ? sheet in a dynamic manner. As a result, the structural ensemble contains open (active) and closed (inactive) forms, allowing for regulation of chaperone activity through substrate binding. The mutant W61R, which is lethal in Drosophila, adopts only the open state. The receptor motif recognized by MESD was identified by in vitro-binding studies. Furthermore, in vivo functional evidence for the relevance of the identified contact sites in MESD is provided.
A considerable body of literature has reported on emotion perception deficits and the relevance of these impairments in persons with depression and bipolar disorder. Fifty-one studies published between 1981-February 2009 were examined regarding emotion perception abilities between patient and control groups, and potential methodological, demographic and clinical moderators. Studies were identified through a computerized literature search of the MEDLINE, PsychINFO, and PubMed databases. The Meta-analysis Of Observational Studies in Epidemiology (MOOSE) standard (Stroup et al., 2000) was followed in the extraction of relevant studies and data. Data on emotion perception, methodology, demographic and clinical characteristics were compiled and analyzed using Comprehensive Meta-Analysis version 2.0 (Biostat, 2005). The meta-analysis revealed a moderate deficit in emotion perception in both bipolar disorder and major depressive disorder, irrespective of task type, diagnosis, age of onset/duration of illness, sex, and hospitalization status. Several factors that moderated the observed impairment include self-reported depression, age at time of testing, and years of education. Emotion perception impairment in bipolar disorder and major depressive disorder represents a moderate and stable deficit that appears to be moderated by a limited number of demographic and clinical factors.
Facial expression is widely used to evaluate emotional impairment in neuropsychiatric disorders. Ekman and Friesens Facial Action Coding System (FACS) encodes movements of individual facial muscles from distinct momentary changes in facial appearance. Unlike facial expression ratings based on categorization of expressions into prototypical emotions (happiness, sadness, anger, fear, disgust, etc.), FACS can encode ambiguous and subtle expressions, and therefore is potentially more suitable for analyzing the small differences in facial affect. However, FACS rating requires extensive training, and is time consuming and subjective thus prone to bias. To overcome these limitations, we developed an automated FACS based on advanced computer science technology. The system automatically tracks faces in a video, extracts geometric and texture features, and produces temporal profiles of each facial muscle movement. These profiles are quantified to compute frequencies of single and combined Action Units (AUs) in videos, and they can facilitate a statistical study of large populations in disorders known to impact facial expression. We derived quantitative measures of flat and inappropriate facial affect automatically from temporal AU profiles. Applicability of the automated FACS was illustrated in a pilot study, by applying it to data of videos from eight schizophrenia patients and controls. We created temporal AU profiles that provided rich information on the dynamics of facial muscle movements for each subject. The quantitative measures of flatness and inappropriateness showed clear differences between patients and the controls, highlighting their potential in automatic and objective quantification of symptom severity.
Staphylococcus aureus is a major human pathogen. Superantigens (SAg) are important virulence factors in S. aureus, but the regulation of SAg gene expression is largely unknown. Using 2 sequenced S. aureus strains (COL and Newman) and 4 clinical isolates, regulation of gene expression was investigated in more detail for 12 SAgs. The SAg-encoding genes were expressed in a growth phase-dependent manner: while the egc operon was mainly transcribed at low optical densities, the transcription of seb was induced at high optical densities. The transcript levels of sea, sek, seq, sep, and tst-1 did not change significantly during growth. The T cell-mitogenic activity of supernatants correlated with the transcription data. SaeRS and ?(B) strongly influenced SAg gene transcription. ?(B) activated transcription of seh, tst-1, and of the egc operon. A possible ?(B)-dependent promoter was identified in front of the egc operon. In contrast, a loss of ?(B) enhanced the transcript level of seb, suggesting an indirect effect of the alternative sigma factor on the transcription of this gene. Transcriptional studies of an saeS mutant showed that the two-component system only activates transcription of seb. The influence of ?(B) and SaeRS on the expression of SAg genes was validated by T cell proliferation assays. For sigB mutants in different strains, different effects on the T cell-mitogenic potential were observed depending on the SAg gene repertoire of the isolates.
Previous investigations of the influence of paranoia on facial affect recognition in schizophrenia have been inconclusive as some studies demonstrate better performance for paranoid relative to non-paranoid patients and others show that paranoid patients display greater impairments. These studies have been limited by small sample sizes and inconsistencies in the criteria used to define groups. Here, we utilized an established emotion recognition task and a large sample to examine differential performance in emotion recognition ability between patients who were actively paranoid (AP) and those who were not actively paranoid (NAP). Accuracy and error patterns on the Penn Emotion Recognition test (ER40) were examined in 132 patients (64 NAP and 68 AP). Groups were defined based on the presence of paranoid ideation at the time of testing rather than diagnostic subtype. AP and NAP patients did not differ in overall task accuracy; however, an emotion by group interaction indicated that AP patients were significantly worse than NAP patients at correctly labeling neutral faces. A comparison of error patterns on neutral stimuli revealed that the groups differed only in misattributions of anger expressions, with AP patients being significantly more likely to misidentify a neutral expression as angry. The present findings suggest that paranoia is associated with a tendency to over attribute threat to ambiguous stimuli and also lend support to emerging hypotheses of amygdala hyperactivation as a potential neural mechanism for paranoid ideation.
Negative symptoms in schizophrenia include diminished ability to communicate, motivate, and socialize as potentially debilitating aspects of the illness that are associated with long-term impairment. Despite such burden, the domain has been underrepresented in drug development and treatment research. In this article, we review research regarding pharmacotherapy for negative symptoms, with a focus on studies published during the past 2 years. Clearly positive studies were limited to N-methyl-D-aspartate agonists, while antipsychotics and antidepressants did not show substantial benefit, and cognitive enhancers have yielded mixed results. Proof-of-concept studies of other agents such as minocycline and omega fatty acids yielded promising, albeit preliminary findings that warrant replication. Study outcomes and designs are discussed along with implications for future research.
A measurement system based on digital holography for the simultaneous measurement of out-of-plane and radial in-plane displacement fields for the assessment of residual stress is presented. Two holograms are recorded at the same time with a single image taken by a digital camera, allowing the separate evaluation of in-plane and out-of-plane movement. An axis-symmetrical diffractive optical element is used for the illumination of the object, which causes radial sensitivity vectors. By the addition and, respectively, the subtraction, of the four phase maps calculated from two camera frames, the in-plane and out-of-plane deformation of an object can be calculated separately. The device presented is suitable for high-speed, high-resolution measurement of residual stress. In addition to the setup, first measurement results and a short comparison to a mature digital speckle pattern interferometry setup are shown.
Paraneoplastic disorders of the CNS result from immune responses to neuronal proteins expressed by tumors found elsewhere in the body. Limbic encephalitis, one of the most common manifestations of paraneoplastic disorders, is characterized by rapid onset of psychiatric and neurological symptoms that often culminate in severe neurological deterioration. Recent work has described paraneoplastic syndromes with prominent, and sometimes isolated, psychiatric symptoms for which patients are fi rst seen by a psychiatrist. Here the authors review the existing literature on psychiatric and behavioral manifestations of paraneoplastic disorders, the cellular mechanisms underlying these syndromes, and current treatment and outcomes. They also discuss the broad behavioral findings that highlight the need for psychiatrists to be aware of initial presentations of paraneoplastic disorders.
Impaired facial emotion expression is central to schizophrenia. Extensive work has quantified these differences, but it remains unclear how patient expressions are perceived by their healthy peers and other non-trained individuals. This study examined how static facial expressions of posed and evoked emotions of patients and controls are recognized by naïve observers.
An alignment of upstream regions of anaerobically induced genes in Staphylococcus aureus revealed the presence of an inverted repeat, corresponding to Rex binding sites in Streptomyces coelicolor. Gel shift experiments of selected upstream regions demonstrated that the redox-sensing regulator Rex of S. aureus binds to this inverted repeat. The binding sequence--TTGTGAAW(4)TTCACAA--is highly conserved in S. aureus. Rex binding to this sequence leads to the repression of genes located downstream. The binding activity of Rex is enhanced by NAD+ while NADH, which competes with NAD+ for Rex binding, decreases the activity of Rex. The impact of Rex on global protein synthesis and on the activity of fermentation pathways under aerobic and anaerobic conditions was analysed by using a rex-deficient strain. A direct regulatory effect of Rex on the expression of pathways that lead to anaerobic NAD+ regeneration, such as lactate, formate and ethanol formation, nitrate respiration, and ATP synthesis, is verified. Rex can be considered a central regulator of anaerobic metabolism in S. aureus. Since the activity of lactate dehydrogenase enables S. aureus to resist NO stress and thus the innate immune response, our data suggest that deactivation of Rex is a prerequisite for this phenomenon.
Schizophrenia patients display impaired performance and brain activity during facial affect recognition. These impairments may reflect stimulus-driven perceptual decrements and evaluative processing abnormalities. We differentiated these two processes by contrasting responses to identical stimuli presented under different contexts. Seventeen healthy controls and 16 schizophrenia patients performed an fMRI facial affect detection task. Subjects identified an affective target presented amongst foils of differing emotions. We hypothesized that targeting affiliative emotions (happiness, sadness) would create a task demand context distinct from that generated when targeting threat emotions (anger, fear). We compared affiliative foil stimuli within a congruent affiliative context with identical stimuli presented in an incongruent threat context. Threat foils were analysed in the same manner. Controls activated right orbitofrontal cortex (OFC)/ventrolateral prefrontal cortex (VLPFC) more to affiliative foils in threat contexts than to identical stimuli within affiliative contexts. Patients displayed reduced OFC/VLPFC activation to all foils, and no activation modulation by context. This lack of context modulation coincided with a 2-fold decrement in foil detection efficiency. Task demands produce contextual effects during facial affective processing in regions activated during affect evaluation. In schizophrenia, reduced modulation of OFC/VLPFC by context coupled with reduced behavioural efficiency suggests impaired ventral prefrontal control mechanisms that optimize affective appraisal.
Recognition memory of faces is impaired in patients with schizophrenia, as is the neural processing of threat-related signals, but how these deficits interact to produce symptoms is unclear. The authors used an affective face recognition paradigm to examine possible interactions between cognitive and affective neural systems in schizophrenia.
A new approach for the detection of virulence factors of Staphylococcus aureus and Staphylococcus epidermidis using an electrical protein array chip technology is presented. The procedure is based on an enzyme-linked sandwich immunoassay, which includes recognition and binding of virulence factors by specific capture and detection antibodies. Detection of antibody-bound virulence factors is achieved by measuring the electrical current generated by redox recycling of an enzymatically released substance. The current (measured in nanoampere) corresponds to the amount of the target molecule in the analyzed sample. The electrical protein chip allows for a fast detection of Staphylococcus enterotoxin B (SEB) of S. aureus and immunodominant antigen A homologue (IsaA homologue) of S. epidermidis in different liquid matrices. The S. aureus SEB virulence factor could be detected in minimal medium, milk, and urine in a concentration of 1 ng/ml within less than 23 min. Furthermore, a simultaneous detection of SEB of S. aureus and IsaA homologue of S. epidermidis in a single assay could be demonstrated.
Probiotic bacteria are thought to play an important role in the digestive system and therefore have to survive the passage from stomach to intestines. Recently, a novel approach to simulate the passage from stomach to intestines in a single bioreactor was developed. The advantage of this automated one reactor system was the ability to test the influence of acid, bile salts and pancreatin.Lactobacillus gasseri K7 is a strain isolated from infant faeces with properties making the strain interesting for cheese production. In this study, a single reactor system was used to evaluate the survival of L. gasseri K7 and selected bifidobacteria from our collection through the stomach-intestine passage.
Part of the innate defense of bronchial epithelia against bacterial colonization is regulated secretion of salt, water, and mucus as well as defensins and cytokines involving MAP kinase activation and alterations in early gene expression. We tested two different types of immortalized human airway epithelial cells (S9, 16HBE14o-) for activation of Erk-type MAP kinases and for expression of c-Fos on treatment with Staphylococcus aureus culture supernatants from the stationary growth phase [optical density (OD)(540 nm) = 10] or with recombinant S. aureus hemolysins A and B (Hla, Hlb). OD10 supernatants activated Erk-type MAP kinases and c-Fos expression in a concentration-dependent manner. Hla induced Erk-type kinase phosphorylation in S9 but not in 16HBE14o- cells. Hlb induced Erk activation in either cell type. Basal and stimulated levels of Erk-type MAP kinase phosphorylation were sensitive to the Mek1 inhibitor PD-98059, indicating that the bacterial products activated the entire signaling cascade that coregulates IL-8 induction and secretion. While c-Fos expression was enhanced by OD10 supernatants, Hla, and Hlb in S9 cells, 16HBE14o- cells responded to OD10 supernatant and Hlb but not to Hla. In S9 cells, PD-98059 suppressed c-Fos upregulation by OD10 supernatant, Hla, or Hlb, indicating that c-Fos expression requires activation of Erk-type MAP kinases. In 16HBE14o- cells, however, c-Fos expression by OD10 supernatant was sensitive to PD-98059, while that induced by Hlb was not. This indicates that ingredients of OD10 supernatants other than Hla or Hlb are activating Erk-type MAP kinases in 16HBE14o- cells and that other intracellular signaling systems apart from Erk-type MAP kinases contribute to Hlb-mediated regulation of c-Fos. Thus interaction of bacterial factors with airway epithelial cells may be highly cell type specific.
Part of the innate defence of bronchial epithelia against bacterial colonization is secretion of salt and water which generally depends on coordinated actions of receptor-mediated cAMP- and calcium signalling. The hypothesis that Staphylococcus aureus-virulence factors interfere with endogenous signals in host cells was tested by measuring agonist-mediated changes in [Ca(2+)](i) in S9 cells upon pre-incubation with bacterial secretory products. S9 cells responded to mAChR-activation with calcium release from intracellular stores and capacitative calcium influx. Treatment of cells with culture supernatants of S. aureus (COL) or with recombinant alpha-hemolysin (Hla) resulted in time- and concentration-dependent changes in [Ca(2+)](i). High concentrations of Hla (2000 ng/ml) resulted in elevations in [Ca(2+)](i) elicited by accelerated calcium influx. A general Hla-mediated permeabilization of S9 cell membranes to small molecules, however, did not occur. Lower concentrations of Hla (200 ng/ml) induced a reduction in [Ca(2+)](i)-levels during the sustained plateau phase of receptor-mediated calcium signalling which was abolished by pre-incubation of cells with carboxyeosin, an inhibitor of the plasma membrane calcium-ATPase. This indicates that low concentrations of Hla change calcium signalling by accelerating pump-driven extrusion of Ca(2+) ions. In vivo, such a mechanism may result in attenuation of calcium-mediated cellular defence functions and facilitation of bacterial adherence to the bronchial epithelium.
A considerable body of literature has reported on emotion perception deficits and the relevance to clinical symptoms and social functioning in schizophrenia. Studies published between 1970-2007 were examined regarding emotion perception abilities between patient and control groups and potential methodological, demographic, and clinical moderators. DATA SOURCES AND REVIEW: Eighty-six studies were identified through a computerized literature search of the MEDLINE, PsychINFO, and PubMed databases. A quality of reporting of meta-analysis standard was followed in the extraction of relevant studies and data. Data on emotion perception, methodology, demographic and clinical characteristics, and antipsychotic medication status were compiled and analyzed using Comprehensive Meta-analysis Version 2.0 (Borenstein M, Hedges L, Higgins J and Rothstein H. Comprehensive Meta-analysis. 2. Englewood, NJ: Biostat; 2005).
Schizophrenia patients exhibit abnormalities in several different auditory event-related potential (ERP) measures. It is unclear how these abnormalities relate to each other, since multiple measures are rarely acquired from the same sample. This study addressed two related questions: 1) Are specific auditory ERP measures differentially impaired in schizophrenia? 2) Do abnormalities co-aggregate within the same patients? Nine auditory ERP measures were acquired in a single testing session from 23 schizophrenia patients and 22 healthy subjects. Hierarchical oblique factor analysis revealed that these measures aggregated into four factors, with each loading primarily on a single factor. Patient deficits were observed for two independent factors: N100/mismatch negativity (MMN) and P3a/P3b. N100/MMN abnormalities were associated with symptoms of alogia and formal thought disorder. P3a/P3b abnormalities were associated with avolition, attentional disturbances and delusions. We conclude that deficits in different ERP measures of early sensory processing at the level of the auditory cortex co-occur in patients. These likely represent a single differential deficit indexing the physiological abnormality underlying impaired language and verbal processing. This is relatively independent of a higher cortical deficit that mediates cognitive stimulus evaluation and underlies deficits in motivation, attention and reality testing. Such multidimensional profiling of ERP abnormalities may help to clarify the clinical and genetic heterogeneity of schizophrenia.
The tobacco alkaloid nicotine is responsible for addiction to tobacco and supposed to contribute to tobacco carcinogensis, too. Recently, genotoxic effects of nicotine have been reported in human cells from blood and upper aerodigestive tract. Because of nicotine accumulation in saliva, the study of possible in vitro genotoxic effects of nicotine have been extended to human salivary gland cells. Specimens of parotid glands of 10 tumor patients were obtained from tumor-free tissue. Single cells were prepared by enzymatic digestion immediately after surgery and exposed for 1h to 0.125-4.0mM of nicotine. Possible genotoxic effects were determined by the Comet assay using the % DNA in tail (DT) as a reliable indicator of DNA damage. Nicotine induced a significant dose-dependent increase of DNA migration in parotid gland single-cells. The mean DT was 1.12-fold (0.125mM) to 2.24-fold (4.0mM) higher compared to control. The lowest concentration eliciting significant DNA damage within 1h, 0.25mM nicotine, is only 10-fold higher than maximal concentrations of nicotine reported in saliva after unrestricted smoking. Although conclusive evidence for a carcinogenic potential of nicotine is still lacking, the safety of long-term nicotine replacement therapy should be carefully monitored.
Pancreatic endocrine tumors represent morphologically and biologically heterogeneous neoplasms. Well-differentiated endocrine tumors (benign or of uncertain behavior) can be distinguished from well-differentiated and poorly differentiated endocrine carcinomas. Although many well-differentiated endocrine carcinomas show rather low rates of tumor growth, more than two-thirds of pancreatic endocrine carcinomas display distant metastases at the time of diagnosis. As the currently applied therapies beyond surgery only achieve partial or complete response rates of approximately 15%, additional chemotherapeutic targets are needed, especially in the therapy of inoperable and progressive pancreatic endocrine carcinomas.
Attentional and sensorimotor gating deficits in human depression are observed as residual symptoms irrespective of antidepressant treatment. Clinical studies point to a benefit of modafinil in depression. No data are available on modafinil effects in depression-like animal models.
Epstein-Barr virus (EBV) is present in all cases of endemic Burkitt lymphoma (BL) but in few European/North American sporadic BLs. Gene expression arrays of sporadic tumors have defined a consensus BL profile within which tumors are classifiable as "molecular BL" (mBL). Where endemic BLs fall relative to this profile remains unclear, since they not only carry EBV but also display one of two different forms of virus latency. Here, we use early-passage BL cell lines from different tumors, and BL subclones from a single tumor, to compare EBV-negative cells with EBV-positive cells displaying either classical latency I EBV infection (where EBNA1 is the only EBV antigen expressed from the wild-type EBV genome) or Wp-restricted latency (where an EBNA2 gene-deleted virus genome broadens antigen expression to include the EBNA3A, -3B, and -3C proteins and BHRF1). Expression arrays show that both types of endemic BL fall within the mBL classification. However, while EBV-negative and latency I BLs show overlapping profiles, Wp-restricted BLs form a distinct subgroup, characterized by a detectable downregulation of the germinal center (GC)-associated marker Bcl6 and upregulation of genes marking early plasmacytoid differentiation, notably IRF4 and BLIMP1. Importantly, these same changes can be induced in EBV-negative or latency I BL cells by infection with an EBNA2-knockout virus. Thus, we infer that the distinct gene profile of Wp-restricted BLs does not reflect differences in the identity of the tumor progenitor cell per se but differences imposed on a common progenitor by broadened EBV gene expression.
After ingestion, pharmaceuticals are excreted unchanged or metabolized. They subsequently arrive in conventional wastewater treatment plants and are then released into the environment, often without undergoing any degradation. Conventional treatment plants can be upgraded with post treatment, alternatively the removal of pharmaceuticals could be achieved directly at point sources. In the European project PILLS, several solutions for decentralized treatment of pharmaceuticals at hospitals were investigated at both pilot plant and full scale, and were then compared to conventional and upgraded centralized treatment plants using Life Cycle Assessment (LCA). Within the scope of the study, pharmaceuticals were found to have a comparatively minor environmental impact. As a consequence, an additional post treatment does not provide significant benefits. In the comparison of post treatment technologies, ozonation and activated carbon performed better than UV. These results suffer however from high uncertainties due to the assessment models of the toxicity of pharmaceuticals in LCA. Our results should therefore be interpreted with caution. LCA is a holistic approach and does not cover effects or issues on a local level, which may be highly relevant. We should therefore apply the precautionary ALARA principle (As Low As Reasonably Achievable) and not conclude that the effect of pharmaceuticals is negligible in the environment.
The ?-proteobacterium Caulobacter crescentus inhabits low-nutrient environments and can tolerate certain levels of heavy metals in these sites. It has been reported that C. crescentus responds to exposure to various heavy metals by altering the expression of a large number of genes.
A converging body of clinical and empirical reports indicates that autism features elevated rates of paranoia comparable to those of individuals with paranoid schizophrenia. However, the distinct developmental courses and symptom manifestations of these two disorders suggest that the nature of paranoid ideation may differ between them in important and meaningful ways. To evaluate this hypothesis, we compared patterns of responses on the Paranoia Scale between actively paranoid individuals with schizophrenia (SCZP), individuals with schizophrenia who were not actively paranoid (SCZNP), adults with an Autism Spectrum Disorder (ASD), and healthy controls. Despite an overall similar level of heightened paranoia in the ASD and SCZP groups, discriminant correspondence analysis (DiCA) revealed that these groups were characterized by unique underlying factors. Paranoia in the SCZP group was defined by a factor based upon victimization, suspicion, and threat of harm. Whereas paranoia in the ASD group was partially characterized by this factor, it was distinguished from SCZP by an additional pattern of responses reflective of increased social cynicism. These findings indicate that paranoia in ASD is supported by qualitative factors distinct from schizophrenia and highlight mechanistic differences in the formation of paranoid ideation that may inform the development of disorder-specific treatments.
Cyclic electrodeposition of platinum and copper enables the fabrication of high surface area electrodes (roughness factors of >3000) by multiple alternation of alloy co-deposition and dealloying of copper from the just-fabricated alloy layers. The underlying processes, resulting electrode structures, and their applicability to potentially implantable glucose fuel cells are discussed.
While olfactory deficits have been reported in schizophrenia and youths at-risk for psychosis, few studies have linked these deficits to current pathophysiological models of the illness. There is evidence that disrupted cyclic adenosine 3,5-monophosphate (cAMP) signaling may contribute to schizophrenia pathology. As cAMP mediates olfactory signal transduction, the degree to which this disruption could manifest in olfactory impairment was ascertained. Odor-detection thresholds to two odorants that differ in the degree to which they activate intracellular cAMP were assessed in clinical risk and low-risk participants.
In recent years, there have been increasing efforts to develop early detection and prevention strategies for patients at risk of the development of psychotic disorders. These efforts have led to improved recognition and characterization of psychotic symptoms in youth. This review focuses on the evaluation of children and adolescents with psychotic symptoms who are experiencing functional impairment but who do not meet current criteria for schizophrenia. For this article, emphasis is placed on the evaluation of symptoms, differential diagnosis, and consideration of potential interventions.
Emotion perception (EP) is impaired in schizophrenia, is stable across clinical state, resistant to antipsychotic treatment and linked to symptom severity. Given its pervasive nature, there is a need to quantitatively examine whether this dysfunction impacts functional outcomes. We used a meta-analytic strategy to combine results from several studies and examine synthesized effect sizes.
Diffuse large B-cell lymphoma is the most frequent type of B-cell lymphoma in adult patients but also occurs in children. Patients are currently assigned to therapy regimens based on arbitrarily chosen age limits only (eg, 18 or 60 years) and not biologically justified limits. A total of 364 diffuse large B-cell lymphomas and related mature aggressive B-cell lymphomas other than Burkitt lymphoma from all age groups were analyzed by comprehensive molecular profiling. The probability of several biologic features previously reported to be associated with poor prognosis in diffuse large B-cell lymphoma, such as ABC subtype, BCL2 expression, or cytogenetic complexity, increases with age at diagnosis. Similarly, various genetic features, such as IRF4 translocations, gains in 1q21, 18q21, 7p22, and 7q21, as well as changes in 3q27, including gains and translocations affecting the BCL6 locus, are significantly associated with patient age, but no cut-offs between age groups could be defined. If age was incorporated in multivariate analyses, genetic complexity lost its prognostic significance, whereas the prognostic impact of ABC subtype and age were additive. Our data indicate that aging is a major determinant of lymphoma biology. They challenge current concepts regarding both prognostic biomarkers and treatment stratification based on strict age cut-offs.
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