Miracle-dz/UniFAR-FTUs huggingface dataset:
Holoclone Forming Cells from Pancreatic Cancer Cells Enrich Tumor Initiating Cells and Represent a Novel Model for Study of Cancer Stem Cells

Background Pancreatic cancer is one of the direct causes of cancer-related death. High level of chemoresistance is one of the major obstacles of clinical treatment. In recent years, cancer stem cells have been widely identified and indicated as the origin of chemoresistance in multi-types of solid tumors. Increasing evidences suggest that cancer stem cells reside in the cells capable of forming holoclones continuously. However, in pancreatic cancer, holoclone-forming cells have not been characterized yet. Therefore, the goal of our present study was to indentify the holoclone-forming pancreatic cancer stem cells and develop an in vitro continuous colony formation system, which will greatly facilitate the study of pancreatic cancer stem cells. Methodology/Principal Findings Pancreatic cancer cell line BxPC3 was submitted to monoclonal cultivation to generate colonies. Based on the morphologies, colonies were classified and analyzed for their capacities of secondary colony formation, long-term survival in vitro, tumor formation in vivo, and drug resistance. Flowcytometry and quantitative RT-PCR were performed to detect the expression level of cancer stem cells associated cell surface markers, regulatory genes and microRNAs in distinct types of colonies. Three types of colonies with distinct morphologies were identified and termed as holo-, mero-, and paraclones, in which only holoclones generated descendant colonies of all three types in further passages. Compared to mero- and paraclones, holoclones possessed higher capacities of long-term survival, tumor initiation, and chemoresistance. The preferential expression of cancer stem cells related marker (CXCR4), regulatory genes (BMI1, GLI1, and GLI2) and microRNAs (miR-214, miR-21, miR-221, miR-222 and miR-155) in holoclones were also highlighted. Conclusions/Significance Our results indicate that the pancreatic tumor-initiating cells with high level of chemoresistance were enriched in holoclones derived from BxPC3 cell line. Generation of holoclones can serve as a novel model for studying cancer stem cells, and attribute to developing new anti-cancer drugs.
Living with a spoiled identity : HIV positive women talk of stigma

Women have been identified as being at greater risk in South Africa's growing HIV epidemic. Stigma contributes to the growing epidemic, as it creates a "spoiled identity"; making HIV positive individuals reluctant to become identified and seek appropriate care. The purpose of this study is to begin to explore how women experience and deal with AIDS stigma under conditions where they have little support. In-depth, narrative interviews were conducted with ten HIV -positive women, living in a poor, black township in Cape Town. The study used both Social Constructionist and Psychoanalytic theory to understand the impact that their "spoiled identity" had on the emotional lives of these women. The study elicited women's narratives as they talked about the circumstances surrounding their diagnosis, their subsequent interaction with their family and community, and their experiences of living with a spoiled identity. The analysis suggested that the women drew on negative social discourses around HIV, which were then internalized, to become part of the self. However, the narratives also indicated the women's resistance to their stigmatised identity. The narratives illustrated their attempts to fend off the 'spoiled identity' by splitting ofIthese bad representations and projecting them outside of themselves. Un ive rsi ty of Ca pe To wn
Genetic Evidence for a Phosphorylation-Independent Signal Transduction Mechanism within the Bacillus subtilis Stressosome

The stressosome is a 1.8 MDa cytoplasmic complex that controls diverse bacterial signaling pathways. Its role is best understood in Bacillus subtilis, where it activates the σB transcription factor in response to a variety of sharp environmental challenges, including acid, ethanol, heat or salt stress. However, details of the signaling mechanism within the stressosome remain uncertain. The core of the complex comprises one or more members of the RsbR co-antagonist family together with the RsbS antagonist protein, which binds the RsbT kinase in the absence of stress. As part of the response, RsbT first phosphorylates the RsbRA co-antagonist on T171 and then RsbS on S59; this latter event correlates with the stress-induced release of RsbT to activate downstream signaling. Here we examine the in vivo consequence of S59 phosphorylation in a model strain whose stressosome core is formed solely with the RsbRA co-antagonist and RsbS. A phosphorylation-deficient S59A substitution in RsbS blocked response to mild stress but had declining impact as stress increased: with strong ethanol challenge response with S59A was 60% as robust as with wild type RsbS. Genetic analysis narrowed this S59-independent activation to the stressosome and established that significant signaling still occurred in a strain bearing both the T171A and S59A substitutions. We infer that S59 phosphorylation increases signaling efficiency but is not essential, and that a second (or underlying) mechanism of signal transduction prevails in its absence. This interpretation nullifies models in which stressosome signaling is solely mediated by control of RsbT kinase activity toward S59.
Incidence of lymphoproliferative disorders in patients with celiac disease

Prior studies describe an increased incidence of lymphoma in celiac disease. However, few studies differentiate among lymphoproliferative disorders (LPDs). Our aim was to determine incidences of LPD subtypes in celiac disease patients, describe patterns of celiac disease presentation in patients who develop LPD, and compare survival in patients with various LPD subtypes. We conducted a retrospective cohort study of adults with biopsy‐proven celiac disease seen at a US referral center from 1981 to 2010, identified patients with comorbid LPD, and calculated standardized incidence ratios (SIR) for each LPD subtype. In our cohort of 1,285 patients with celiac disease, there were 40 patients with LPD [SIR = 6.48, 95% confidence interval (CI) = 4.62–8.64] including 33 with non‐Hodgkin lymphoma (NHL, SIR = 6.91, 95% CI = 4.26–8.28). The incidences of NHL subtypes including enteropathy‐associated T‐cell (EATL, n = 12), non‐EATL T‐cell (SIR = 22.43, 95% CI = 7.08–46.41), diffuse large B‐cell (SIR = 5.37, 95% CI = 1.93–10.52), mantle cell (SIR = 32.21, 95% CI = 6.07–78.97), and marginal zone (SIR = 37.17, 11.73–76.89) lymphoma remained significantly elevated when only those diagnosed with celiac before LPD were considered (n = 24, NHL SIR = 4.47, 95% CI = 2.86–6.44). Patients who developed LPD were older at time of celiac disease diagnosis (57.9 ± 15.5 versus 42.5 ± 17.4 years, P < 0.0001) and more likely to present with diarrhea (60.0% versus 39.8% P = 0.016), abdominal pain (17.5% versus 5.5% P = 0.0046), and/or weight loss (12.5% versus 4.0%, P = 0.028). EATL patients had a shorter average survival than non‐EATL NHL patients (3.2 versus 15.0 years, P = 0.016). The incidence of LPD is increased in celiac disease patients. Those diagnosed later in life who present with symptoms of malabsorption are more likely to be diagnosed with LPD. Am. J. Hematol. 2012. © 2012 Wiley Periodicals, Inc.
Matrix metalloproteinase 8 deficiency in mice exacerbates inflammatory arthritis through delayed neutrophil apoptosis and reduced caspase 11 expression.

OBJECTIVE Neutrophil accumulation is balanced by both cell infiltration and cell clearance, the controls of which are pivotal in the pathogenesis of rheumatoid arthritis (RA) and other chronic inflammatory diseases. Of the neutrophil-specific proteases, matrix metalloproteinase 8 (MMP-8; also known as neutrophil collagenase or collagenase 2) is traditionally viewed as being crucial for collagen degradation and hence cell migration and infiltration. This study was undertaken to examine the role of MMP-8 in a murine model of spontaneous RA. METHODS MMP-8(-/-) mice were backcrossed onto the Fas-defective MRL/lpr background, a mouse strain characterized by systemic autoimmunity including spontaneous autoimmune arthritis. Arthritis was induced with Freund's complete adjuvant and clinical disease and histologic parameters were assessed. RESULTS MMP-8(-/-) mice had earlier and more severe joint inflammation than their MMP-8(+/+) counterparts, coupled with a massive accumulation of neutrophils in synovial tissue, an unexpected result considering the commonly held view that MMP-8 has important extracellular matrix-degradative functions. Protease and protease inhibitor analysis of MMP-8(-/-) mouse neutrophils by CLIP-CHIP microarray revealed very little additional change in protease levels except for low expression of the apoptosis initiator caspase 11. This was confirmed at the protein level in unstimulated, lipopolysaccharide-treated, and interferon-γ-treated MMP-8(-/-) mouse neutrophils. Downstream of caspase 11, the activity of the apoptosis executioner caspase 3 was consequently reduced in MMP-8(-/-) mouse neutrophils, translating to reduced neutrophil apoptosis and cell accumulation compared with wild-type mouse cells. CONCLUSION Our findings indicate that MMP-8 is not essential for neutrophil migration in arthritis and likely other autoimmune diseases. Rather, MMP-8 is important for normal rates of neutrophil apoptosis and hence regulates cell clearance. Because MMP-8 deficiency leads to an exaggerated accumulation of neutrophil infiltrates due to delayed apoptosis and concurrent pathologic changes associated with dramatically increased neutrophil infiltration, MMP-8 is antiinflammatory and therefore a drug antitarget in the treatment of arthritis.
Item‐Level Frame‐Of‐Reference Effects in Personality Testing: An Investigation of Incremental Validity in an Organizational Setting

A recent line of research has investigated the frame-of-reference effect on personality scale scores, in which self-report personality items are contextualized to the specific performance setting (e.g., work, school) within which the performance criterion is gathered. Contextualization has been shown to increase both the reliability and the criterion-related validity of the personality scale scores by facilitating the self-presentation of respondents, and by more closely measuring the personality construct relevant to the performance domain. The current research extends this area of personality research in two ways. First, this study tests the generalizability of the effectiveness of item-level contextualization within an organizational setting. Second, this study also provides the necessary test of the incremental validity of this contextualized approach to personality measurement above and beyond the traditional, noncontextualized approach. The results confirm that a work-specific personality measure, contextualized at the item level, adds to the prediction of job performance above and beyond that obtained by a noncontextual measure of the same personality traits. Practical and theoretical implications are discussed.
Bodily sensibility: vocabularies of the discredited male body

Warning: this article contains strong language. This paper explores how men might interpret and respond to a masculine bodily aesthetic in the wake of the putative obesity epidemic that reportedly affects most men in Western nations. This aesthetic, legitimated through discourses of health and risk management, is also shaped by popular representations of lean, toned and hard male bodies and their antithesis: the grotesque, ‘morbidly obese’ (sic) body. Empirically, this paper benefits from insights generated during a slimming club ethnography in Northeast England and in-depth interviews with men, although valuable observations were also made at informal situations where talk about weight and bodies was commonplace. In particular, the paper explores the use of vulgarised idioms (e.g. ‘fat bastard’) that emerged among men when constructing masculine identities, and other people who could shape or spoil their identities. A four-fold ideal-type typology is presented in order to understand how men, in association with other people, reproduced and resisted the aesthetic as part of their gendered identity work. The typology highlights what we call a bodily sensibility and vocabularies of the discredited body, which reflect and provide ways of managing everyday life and the stigma of what medicine calls obesity. This is in a culture where war has been declared on obesity and men have increasingly to account for themselves if they are seen to deviate from bodily ideals, or normative embodiment.
Disaster recovery experiences of a South African rural farming community

This study explored the bush fire disaster experiences and coping of South African farmers. Participants consisted of seven male farmers (6 = White Afrikaans-speaking; 1 = Black Tswana-speaking). Data were collected using semi-structured interviews, nine months after the disaster, and analysed thematically. The findings showed that the farmers’ recovery was characterised by three distinct, transitioning phases. The first period involved resource-maintenance coping and emotion-focused coping. The second time period was characterised by meaning making related strategies. Finally, the third time period was charactirised by anxiety over reoccurrence and resource-maintenance coping. The results also suggest that successful coping is reliant on the individual's ability to adapt coping strategies continually, in a context-appropriate manner.
Moral Opinions are Conditional on the Behavior of Others

In social dilemmas individual behavior creates external effects on others. In such situations, a person's opinions concerning right and wrong might influence his behavior. Understanding moral opinions therefore is important. This paper reports on an experiment which shows that moral opinions are conditional on the behavior of others. This is demonstrated by the finding that a large majority of subjects in a public good game experiment report personal normative beliefs that increase with the actual contributions made by group members. This finding is important for the design of policies attempting to sustain public good provisions.
Rapid Enzyme-Linked Immunosorbent Assay for the Detection of Hantavirus-Specific Antibodies in Divergent Small Mammals

We assessed the utility of an enzyme-linked immunosorbent assay (ELISA) for the detection of hantavirus-specific antibodies from sera of Oligoryzomys longicaudatus, the principal reservoir of Andes virus (ANDV), using an antigen previously developed for detection of antibodies to Sin Nombre virus (SNV) in sera from Peromyscus maniculatus. The assay uses a protein A/G horseradish peroxidase conjugate and can be performed in as little as 1.5 hours. Serum samples from Oligoryzomys longicaudatus collected in central-south Chile were used and the assay identified several that were antibody positive. This assay can be used for the rapid detection of antibodies to divergent hantaviruses from geographically and phylogenetically distant rodent species.
Reconciliation and Perpetrator Memories in Cambodia

This article considers the reproduction of perpetrator memories to reflect on processes of reconciliation in Cambodia. The article explores the circulation of memories around local memorial and heritage sites within a former Khmer Rouge (KR) community, Anlong Veng. Anlong Veng was home to several senior KR leaders, two of whom were found guilty of crimes against humanity at the Extraordinary Chambers in the Courts of Cambodia (ECCC). 1 The article draws on ethnographic and interview data to illustrate examples of the traction, limits and dissonances that flow from the ECCC and its attendant discourses of ‘national reconciliation,’ as they intersect with local accounts of the past. I argue that while perpetrator and ‘counter’ memories can have the potential to disrupt reconciliation, the case reveals complexities in the reproduction of memories of atrocity among both victim and perpetrator groups that appear simultaneously ‘unreconciled’ and commensurable to the ECCC project. In doing so, the article opens a critical space for reflections on the place of perpetrator memories in reconciliation initiatives and human rights scholarship.
Miniature optical coherence tomography-ultrasound probe for automatically coregistered three-dimensional intracoronary imaging with real-time display

Abstract. We have developed a novel miniature integrated optical coherence tomography (OCT)-intravascular ultrasound (IVUS) probe, with a 1.5-mm-long rigid part and 0.9-mm outer diameter, for real-time intracoronary imaging of atherosclerotic plaques and guiding of interventional procedures. By placing the OCT ball lens and IVUS transducer back-to-back at the same axial position, this probe can provide automatically coregistered, coaxial OCT-IVUS imaging. To demonstrate its real-time capability, three-dimensional OCT-IVUS imaging of a pig’s coronary artery displaying in polar coordinates, as well as images of three major types of atherosclerotic plaques in human cadaver coronary segments, were obtained using this probe and our upgraded system. Histology validation is also presented.
Mechanical properties of the equine superficial digital flexor tendon relate to specific collagen cross-link levels.

REASONS FOR PERFORMING STUDY Damage to the flexor tendons, particularly the superficial digital flexor tendon (SDFT), is one of the most common musculoskeletal injuries sustained by horses competing in all disciplines. Our previous work has shown that SDFTs from different individuals show a wide variation in mechanical strengths; this is important clinically as it may relate to predisposition to injury. The high mechanical strength of tendon relies on the correct orientation of collagen molecules within fibrils and stabilisation by the formation of chemical cross-links between collagen molecules. It is not known whether the variation in SDFT mechanical properties between individuals relates to differences in collagen cross-link levels. HYPOTHESIS Enzyme-derived, intermolecular cross-linking of tendon collagen correlates with mechanical properties of the SDFT. METHODS SDFTs were collected from 38 horses and mechanically tested to failure. Structural and material properties were calculated from the load/deformation plot and cross-sectional area for each tendon. Following mechanical testing, pyrrolic cross-link levels were measured using a spectrophotometric assay for Ehrlich's reactivity and pyridinoline levels were quantified by HPLC. Cross-link levels were correlated with mechanical properties and statistical significance tested using a Pearson's correlation test. RESULTS Pyrrole cross-link levels showed a significant positive correlation with ultimate stress (P = 0.004), yield stress (P = 0.003) and elastic modulus (P = 0.018) of the tendons, despite being a minor cross-link in these tendons. There was no significant correlation of mechanical properties with either hydroxylysyl- or lysyl-pyridinoline levels. CONCLUSIONS Given the low absolute levels of pyrrole, we suggest that the correlation with high mechanical strength is through an indirect mechanism. Understanding the nature of the relationships between pyrrole cross-links, other matrix characteristics and tendon material properties may allow development of strategies to identify horses at risk from tendon injury and be of value in informing training practices.
DNA-based species delineation in tropical beetles using mitochondrial and nuclear markers

DNA barcoding has been successfully implemented in the identification of previously described species, and in the process has revealed several cryptic species. It has been noted that such methods could also greatly assist in the discovery and delineation of undescribed species in poorly studied groups, although to date the feasibility of such an approach has not been examined explicitly. Here, we investigate the possibility of using short mitochondrial and nuclear DNA sequences to delimit putative species in groups lacking an existing taxonomic framework. We focussed on poorly known tropical water beetles (Coleoptera: Dytiscidae, Hydrophilidae) from Madagascar and dung beetles (Scarabaeidae) in the genus Canthon from the Neotropics. Mitochondrial DNA sequence variation proved to be highly structured, with >95% of the observed variation existing between discrete sets of very closely related genotypes. Sequence variation in nuclear 28S rRNA among the same individuals was lower by at least an order of magnitude, but 16 different genotypes were found in water beetles and 12 genotypes in Canthon, differing from each other by a minimum of two base pairs. The distribution of these 28S rRNA genotypes in individuals exactly matched the distribution of mtDNA clusters, suggesting that mtDNA patterns were not misleading because of introgression. Moreover, in a few cases where sequence information was available in GenBank for morphologically defined species of Canthon, these matched some of the DNA-based clusters. These findings demonstrate that clusters of close relatives can be identified readily in the sequence variation obtained in field collected samples, and that these clusters are likely to correspond to either previously described or unknown species. The results suggest that DNA-assisted taxonomy will not require more than a short fragment of mtDNA to provide a largely accurate picture of species boundaries in these groups. Applied on a large scale, this DNA-based approach could greatly improve the rate of species discovery in the large assemblages of insects that remain undescribed.
Communicative functions of automatic speech in non-fluent dysphasia

Abstract Communicative functions of automatic speech were examined for four acute non-fluent dysphasic subjects and four matched, non-aphasic controls were examined. Verbal output was elicited using different contexts and conversational partners: picture description, dyads, and triads. Results revealed that dysphasic subjects produced a significantly greater number of automatic utterances, primarily representative of recurring utterances, and that they were revised frequently by the dysphasic subjects. Relative to the analysed communicative function categories, the data revealed significant differences between the two groups for the speech act category of ‘answer’ and for the discourse strategy of ‘conversational repair’. Discussions relate to establishing the similarities and dissimilarities between the two groups in their use of automatic speech for communication; the linguistic characteristics of automatic speech; and the effect of paralinguistic variables and context.