The opposite of witchcraft: Evans‐Pritchard and the problem of the person

The principal legacy of Evans‐Pritchard's 1937 ethnography Witchcraft, oracles and magic among the Azande has been to associate debates over the rationality of witchcraft with its social categorization as a facet of misfortune and enmity. In combination with Evans‐Pritchard's own scepticism regarding witches, this allowed the rationality debate to isolate witchcraft as a distinctive special case. This logical exceptionalism was at odds with Evans‐Pritchard's own assertion of witchcraft's ordinariness, and is not supported by comparable ethnography from the Ladakh region of the Himalayas or by the unabridged versions of Oracles, both of which point towards an indigenous understanding of witchcraft as one variation on a spectrum of everyday action and craft. Instead, a revised reading of Oracles suggests that even the most basic quotidian representations of personal agency raise larger questions as to anthropology's understanding of how humans ascribe action and personhood, a debate which stands at the heart of its status as a science.     

Reflections on Grant Evans’ The Politics of Ritual and Remembrance: Laos since 1975

In this article I reflect on Grant Evans’ landmark and influential The Politics of Ritual and Remembrance: Laos since 1975, the way in which this book relates to the transformation from socialism to post‐socialism in the Lao People's Democratic Republic (LPDR), to the crisis of legitimacy of the communist regime, and to issues of social memory, Buddhism, nationalism, iconography, and ethnic minorities. I also consider how other scholars have engaged with The Politics of Ritual and Remembrance both critically and supportively since the publication of the monograph in 1998 . I include in my analysis some observations on Evans’ quite radical change in political views over his career as a student, journalist and academic, culminating in his critique of socialism in general and the LPDR in particular and his controversial sympathy for the Lao monarchy.     

Hunter‐gatherers and human evolution

Although few hunter‐gatherers or foragers exist today, they are well documented in the ethnographic record. Anthropologists have been eager to study them since they assumed foragers represented a lifestyle that existed everywhere before 10,000 years ago and characterized our ancestors into some ill‐defined but remote past. In the past few decades, that assumption has been challenged on several grounds. Ethnographically described foragers may be a biased sample that only continued to exist because they occupied marginal habitats less coveted by agricultural people. 3 In addition, many foragers have been greatly influenced by their association with more powerful agricultural societies. 4 It has even been suggested that Holocene foragers represent a new niche that appeared only with the climatic changes and faunal depletion at the end of the last major glaciation. 5 Despite these issues, the ethnographic record of foragers provides the only direct observations of human behavior in the absence of agriculture, and as such is invaluable for testing hypotheses about human behavioral evolution. 6 .     

Automation technology and sense of control: a window on human agency

Previous studies have shown that the perceived times of voluntary actions and their effects are perceived as shifted towards each other, so that the interval between action and outcome seems shortened. This has been referred to as 'intentional binding' (IB). However, the generality of this effect remains unclear. Here we demonstrate that Intentional Binding also occurs in complex control situations. Using an aircraft supervision task with different autopilot settings, our results first indicated a strong relation between measures of IB and different levels of system automation. Second, measures of IB were related to explicit agency judgement in this applied setting. We discuss the implications for the underlying mechanisms, and for sense of agency in automated environments.     

Characterization and high‐yield production of non‐N‐glycosylated recombinant human BCMA‐Fc in Pichia pastoris

B‐cell maturation antigen (BCMA) fused at the C‐terminus to the Fc portion of human IgG1 (BCMA‐Fc) blocks B‐cell activating factor (BAFF) and proliferation‐inducing ligand (APRIL)‐mediated B‐cell activation, leading to immune disorders. The fusion protein has been cloned and produced by several engineering cell lines. To reduce cost and enhance production, we attempted to express recombinant human BCMA‐Fc (rhBCMA‐Fc) in Pichia pastoris under the control of the AOX1 methanol‐inducible promoter. To produce the target protein with uniform molecular weight and reduced immunogenicity, we mutated two predicted N‐linked glycosylation sites. The secretory yield was improved by codon optimization of the target gene sequence. After fed‐batch fermentation under optimized conditions, the highest yield (207 mg/L) of rhBCMA‐Fc was obtained with high productivity (3.45 mg/L/h). The purified functional rhBCMA‐Fc possessed high‐binding affinity to APRIL and dose‐dependent inhibition of APRIL‐induced proliferative activity in vitro through three‐step purification. Thus, this yeast‐derived expression method could be a low‐cost and effective alternative to the production of rhBCMA‐Fc in mammalian cell lines.     

Identification and expansion of human osteosarcoma‐cancer‐stem cells by long‐term 3‐aminobenzamide treatment

A novel cancer stem‐like cell line (3AB‐OS), expressing a number of pluripotent stem cell markers, was irreversibly selected from human osteosarcoma MG‐63 cells by long‐term treatment (100 days) with 3‐aminobenzamide (3AB). 3AB‐OS cells are a heterogeneous and stable cell population composed by three types of fibroblastoid cells, spindle‐shaped, polygonal‐shaped, and rounded‐shaped. With respect to MG‐63 cells, 3AB‐OS cells are extremely smaller, possess a much greater capacity to form spheres, a stronger self‐renewal ability and much higher levels of cell cycle markers which account for G1‐S/G2‐M phases progression. Differently from MG‐63 cells, 3AB‐OS cells can be reseeded unlimitedly without losing their proliferative potential. They show an ATP‐binding cassette transporter ABCG2‐dependent phenotype with high drug efflux capacity, and a strong positivity for CD133, marker for pluripotent stem cells, which are almost unmeasurable in MG‐63 cells. 3AB‐OS cells are much less committed to osteogenic and adipogenic differentiation than MG‐63 cells and highly express genes required for maintaining stem cell state (Oct3/4, hTERT, nucleostemin, Nanog) and for inhibiting apoptosis (HIF‐1α, FLIP‐L, Bcl‐2, XIAP, IAPs, and survivin). 3AB‐OS may be a novel tumor cell line useful for investigating the mechanisms by which stem cells enrichment may be induced in a tumor cell line. The identification of a subpopulation of cancer stem cells that drives tumorigenesis and chemoresistance in osteosarcoma may lead to prognosis and optimal therapy determination. Expression patterns of stem cell markers, especially CD133 and ABCG2, may indicate the undifferentiated state of osteosarcoma tumors, and may correlate with unfavorable prognosis in the clinical setting. J. Cell. Physiol. 219: 301–313, 2009. © 2009 Wiley‐Liss, Inc.     

Anti‐inflammaging effects of human alpha‐1 antitrypsin

Inflammaging plays an important role in most age‐related diseases. However, the mechanism of inflammaging is largely unknown, and therapeutic control of inflammaging is challenging. Human alpha‐1 antitrypsin (hAAT) has immune‐regulatory, anti‐inflammatory, and cytoprotective properties as demonstrated in several disease models including type 1 diabetes, arthritis, lupus, osteoporosis, and stroke. To test the potential anti‐inflammaging effect of hAAT, we generated transgenic Drosophila lines expressing hAAT. Surprisingly, the lifespan of hAAT‐expressing lines was significantly longer than that of genetically matched controls. To understand the mechanism underlying the anti‐aging effect of hAAT, we monitored the expression of aging‐associated genes and found that aging‐induced expressions of Relish (NF‐?B orthologue) and Diptericin were significantly lower in hAAT lines than in control lines. RNA‐seq analysis revealed that innate immunity genes regulated by NF‐kB were significantly and specifically inhibited in hAAT transgenic Drosophila lines. To confirm this anti‐inflammaging effect in human cells, we treated X‐ray‐induced senescence cells with hAAT and showed that hAAT treatment significantly decreased the expression and maturation of IL‐6 and IL‐8, two major factors of senescence‐associated secretory phenotype. Consistent with results from Drosophila,RNA‐seq analysis also showed that hAAT treatment significantly inhibited inflammation related genes and pathways. Together, our results demonstrated that hAAT significantly inhibited inflammaging in both Drosophila and human cell models. As hAAT is a FDA‐approved drug with a confirmed safety profile, this novel therapeutic potential may make hAAT a promising candidate to combat aging and aging‐related diseases.     

The crisscrossed agency of a toast: Personhood,individuation and de‐individuation in Luzhou,China

This article addresses debates over individuation in China through consideration of guanxi‐relational feasting in Luzhou, Sichuan. I draw on Ortner's theorisation of subjectivity and agency to probe the often taken‐for‐granted question of cultural personhood which informs social action. Although the social imaginary in Luzhou is increasingly colonised by symbolic individualism, I propose that dominant local notions of personhood and agency, operating within feast practice, continue to define this process. By attending to three aspects of Yan's ‘individualisation thesis’, I demonstrate how local models of person and agency are indispensible to a fuller understanding of social life. Considering the important role ritual speech habits (largely trained in de‐individuating feasting) continue to play in socialising actors to economic institutions and power relationships more generally, individuation in China today remains a largely nominal and aspirational, if symbolically potent and potentially transformative, project.     

An extracellular Leptospira interrogans leucine‐rich repeat protein binds human E‐ and VE‐cadherins

Pathogenic Leptospira bacteria are the causative agents of leptospirosis, a zoonotic disease affecting animals and humans worldwide. These pathogenic species have the ability to rapidly cross host tissue barriers by a yet unknown mechanism. A comparative analysis of pathogens and saprophytes revealed a higher abundance of genes encoding proteins with leucine‐rich repeat (LRR) domains in the genomes of pathogens. In other bacterial pathogens, proteins with LRR domains have been shown to be involved in mediating host cell attachment and invasion. One protein from the pathogenic species Leptospira interrogans, LIC10831, has been previously analysed via X‐ray crystallography, with findings suggesting it may be an important bacterial adhesin. Herein we show that LIC10831 elicits an antibody response in infected animals, is actively secreted by the bacterium, and binds human E‐ and VE‐cadherins. These results provide biochemical and cellular evidences of LRR protein‐mediated host–pathogen interactions and identify a new multireceptor binding protein from this infectious Leptospira species.     

Spectroscopic and in silico study of binding mechanism of cynidine‐3‐O‐glucoside with human serum albumin and glycated human serum albumin

The drug–serum albumin interaction plays a dominant role in drug efficacy and disposition. The glycation of serum albumin that occurs during diabetes may affect its drug‐binding properties in vivo. In order to evaluate the interactivity characteristics of cyanidin‐3‐O‐glucoside (C3G) with human serum albumin (HSA) and glycated human serum albumin (gHSA), this study was undertaken using multiple spectroscopic techniques and molecular modeling analysis. Time‐resolved fluorescence and the thermodynamic parameters indicated that the quenching mechanism was static quenching, and hydrogen bonding and Van der Waals force were the main forces. The protein fluorescence could be quenched by C3G, whereas the polarity of the fluorophore was not obviously changed. C3G significantly altered the secondary structure of the proteins. Furthermore, the interaction force that existed in the HSA–C3G system was greater than that in the gHSA–C3G system. Fluorescence excitation emission matrix spectra, red edge excitation shift, Fourier transform infrared spectroscopy and circular dichroism spectra provided further evidence that glycation could inhibit the binding between C3G and proteins. In addition, molecular modeling analysis supported the experimental results. The results provided more details for the application of C3G in the treatment of diabetes.     

Development and evaluation of human T‐cell leukemia virus‐1 and ‐2 multiplex quantitative PCR

The diagnosis of human T ‐cell leukemia virus type 1 (HTLV‐1) infection in Japan is usually performed by serological testing, but the high rate of indeterminate results from western blotting makes it difficult to assess the infection accurately. Nucleic acid tests for HTLV‐1 and/or HTLV‐2 are used to confirm infection with HTLV‐1 and/or HTLV‐2 and are also used for the follow‐up of HTLV‐1 related diseases. To prepare a highly sensitive method that can discern infection with HTLV‐1 and HTLV‐2, a multiplex quantitative polymerase chain reaction (qPCR) by large‐scale primer screening was developed. Sensitivity and specificity were evaluated by serial dilution of cell lines and by testing with known clinical samples. The resulting multiplex qPCR can detect about four copies of HTLV‐1 provirus per 10⁵ cells. Moreover, HTLV‐1 provirus could be detected in 97.2% (205 of 211) of HTLV‐1 seropositive clinical samples. These sensitivities were sufficiently high compared with the methods reported previously. Also, all the HTLV‐2 seropositive clinical samples tested were found to be positive by this method (three of three). In conclusion, this method can successfully and simultaneously detect both types of HTLV‐1 and HTLV‐2 provirus with extremely high sensitivity.     

miR‐1‐3p and miR‐206 sensitizes HGF‐induced gefitinib‐resistant human lung cancer cells through inhibition of c‐Met signalling and EMT

Hepatocyte growth factor (HGF) overexpression is an important mechanism in acquired epidermal growth factor receptor (EGFR) kinase inhibitor gefitinib resistance in lung cancers with EGFR activating mutations. MiR‐1‐3p and miR‐206 act as suppressors in lung cancer proliferation and metastasis. However, whether miR‐1‐3p and miR‐206 can overcome HGF‐induced gefitinib resistance in EGFR mutant lung cancer is not clear. In this study, we showed that miR‐1‐3p and miR‐206 restored the sensitivities of lung cancer cells PC‐9 and HCC‐827 to gefitinib in present of HGF. For the mechanisms, we demonstrated that both miR‐1‐3p and miR‐206 directly target HGF receptor c‐Met in lung cancer. Knockdown of c‐Met mimicked the effects of miR‐1‐3p and miR‐206 transfections Meanwhile, c‐Met overexpression attenuated the effects of miR‐1‐3p and miR‐206 in HGF‐induced gefitinib resistance of lung cancers. Furthermore, we showed that miR‐1‐3p and miR‐206 inhibited c‐Met downstream Akt and Erk pathway and blocked HGF‐induced epithelial‐mesenchymal transition (EMT). Finally, we demonstrated that miR‐1‐3p and miR‐206 can increase gefitinib sensitivity in xenograft mouse models in vivo. Our study for the first time indicated the new function of miR‐1‐3p and miR‐206 in overcoming HGF‐induced gefitinib resistance in EGFR mutant lung cancer cell.     

Quantitative DY‐maleimide‐based proteomic 2‐DE‐labeling strategies using human skin proteins

Sensitive differential proteomic analysis is challenging and often limited by distinct labeling or tagging strategies. In this study, we have examined the sensitivity, linearity, and photophysical properties of novel protein labeling DY‐maleimide dyes (DY‐505‐MAL, DY‐555‐MAL and DY‐635‐MAL). All MS compatible DY‐maleimide dyes exhibited excellent emission spectra, high sensitivity, and high linearity, when applied to standard 1‐DE protein analysis. Correspondingly, 2‐DE analysis of DY‐635‐MAL or DY‐505‐MAL maximal‐labeled human keratinocyte proteins displayed remarkably high sensitivity. Compared with a standard fluorescent protein stain, DY‐635‐MAL or DY‐505‐MAL 2‐DE analysis demonstrated equally high spot quality with an overall increase in the number of spots detectable (up to threefold higher;>1000 spots/gel). However, as determined with a FLA‐5100 imaging system, comparative MultiGauge, and Delta2D analysis, not all DY‐maleimide dyes possessed DIGE compatible fluorescent emission properties. However, DY‐505‐MAL and DY‐635‐MAL were found to be suitable for more complex, time and gel intensive, focused multiplexing analyses. Notably – as demonstrated with allergen‐stimulated human skin proteins – defined, singular DY‐maleimide dye protein labeling (SDPL) allows high quality, time saving, simple, and reliable differential proteomic examination.     

‘Rules that apply in times of crisis’: time,agency, and norm‐remaking during Nepal's People's War

This article explores how people in the former Maoist heartland of Nepal adopted previously transgressive norms and practices during the decade of the People's War (1996‐2006). By examining the rise in practices of beef‐eating and inter‐caste commensality, this article suggests that the temporal dimension of wartime ‘when different rules apply’ was crucial in making people accept new ideas and break established norms on a scale atypical for the ‘normal’ times of peace. Analysing the agency of Maoist activists, who self‐consciously tried to implement a project of radical social transformation, and those people who were caught in the midst of the Maoist transformative endeavour, this article argues that the contours of the ‘new society’ emerged not only due to revolutionaries’ intentional actions but also because of the ‘exceptional’ nature of wartime, which forced people to radically re‐create their daily lives. By transgressing social norms, ‘ordinary’ people did not deliberately undermine the normative order, but rather responded to the constraints of wartime, when people's agency and ethical choices were mostly driven by the need to secure the survival of their families and ensure the continuity of life itself.     

Chlamydia pneumoniae induces interleukin‐6 and interleukin‐10 in human gingival fibroblasts

Chlamydia pneumoniae is an obligate intracellular Gram‐negative bacterium with a unique biphasic developmental cycle that can cause persistent infections. In humans, Chlamydia causes airway infection and has been implicated in chronic inflammatory diseases, such as asthma and atherosclerosis. In addition, recent studies demonstrated that patients with severe periodontitis can harbor C. pneumoniae, which can increase the risk for a host inflammatory response with weighty clinical sequelae. Previous studies have established that periodontal pathogenic bacteria (i.e. Gram‐negative bacteria) can induce the synthesis and release of cytokines and other inflammatory mediators in human gingival fibroblasts. HGF are resident cells of the periodontium that respond to receptor stimulation by producing a variety of substances including cytokines and growth factors. Our results demonstrate that after 48 hr of incubation with viable C. pneumoniae HGF showed a proliferative response, as seen by both colorimetric MTT assay and direct cell count (30% and 35%, respectively). In addition, HGF incubated with viable or UV light‐inactivated C. pneumoniae organisms showed an increase in the levels of IL‐6 and IL‐10, but not IL‐4; on the contrary, HGF infected with heat‐killed bacteria did not show a significant production of any of the cytokines considered. In conclusion, the present study suggests that C. pneumoniae may modulate the expression of IL‐6 and IL‐10 by human gingival fibroblasts. Further studies are warranted to clarify the molecular mechanisms of C. pneumoniae in the regulation of cytokine expression by host cells and to elaborate the relevant clinical implications.