Kafka at the West Bank checkpoint: de-normalizing the Palestinian encounter before the law

The checkpoint has emerged as a quintessential trope within the contemporary Palestinian imagination, to such an extent that “checkpoint narratives” have arguably come to assume a dangerously “normalized” status as everyday, even iconic features of Palestinian existence. Turning to the films Route 181 by Michel Khleifi and Eyal Sivan, and like twenty impossibles by Annemarie Jacir, this article explores how alternative representations (and theorizations) of checkpoint encounter might serve to “de-normalize” the checkpoint in a way that invites us to interrogate the very nature of the checkpoint apparatus in itself, including the nature of the “law” that it represents. Mobilizing the critical paradigms of the “state of exception” and “homo sacer” drawn from the theoretical work of Giorgio Agamben and the literary work of Franz Kafka, the article argues that apprehension of the enduring oddity and abnormality of the checkpoint serves as a vital mode of critical resistance to the policies of “spatio-cide”, “securitization” and colonialism exercised at the hands of the State of Israel through the checkpoint mechanism

(En)gendering the political: Citizenship from marginal spaces

This introduction sets out the central concerns of this special issue, the relationship between marginality and the political. In doing so it makes the argument that the process of marginalisation, the sites and experiences of ‘marginality’ provide a different lens through which to understand citizenship. Viewing the political as the struggle over belonging it considers how recent studies of citizenship have understood political agency. It argues that marginality can help us understand multiple scales, struggles and solidarities both within and beyond citizenship. Whilst there is a radical potential in much of the existing literature in citizenship studies it is also important to consider political subjectivities and acts which are not subsumed by right claims. Exploring marginality in this way means understanding how subjects are disenfranchised by regimes of citizenship and at the same how time this also (en)genders new political possibilities which are not always orientated towards 'inclusion'. The introduction then sets out how each article contributes to this project

Stress biology:Complexity and multifariousness in health and disease

Preserving and regulating cellular homeostasis in the light of changing environmental conditions or developmental processes is of pivotal importance for single cellular and multicellular organisms alike. To counteract an imbalance in cellular homeostasis transcriptional programs evolved, called the heat shock response, unfolded protein response, and integrated stress response, that act cell-autonomously in most cells but in multicellular organisms are subjected to cell-nonautonomous regulation. These transcriptional programs downregulate the expression of most genes but increase the expression of heat shock genes, including genes encoding molecular chaperones and proteases, proteins involved in the repair of stress-induced damage to macromolecules and cellular structures. Sixty-one years after the discovery of the heat shock response by Ferruccio Ritossa, many aspects of stress biology are still enigmatic. Recent progress in the understanding of stress responses and molecular chaperones was reported at the 12th International Symposium on Heat Shock Proteins in Biology, Medicine and the Environment in the Old Town Alexandria, VA, USA from 28th to 31st of October 2023.</p

Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis.

Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis

“You ain’t gonna get away wit’ this, Django”: Fantasy, fiction and subversion in Quentin Tarantino’s, Django Unchained

From 2009 to 2015, U.S. director, Quentin Tarantino, released three films that were notable for their focus on particular historical events, periods and individuals (Inglorious Basterds 2009; Django Unchained 2012; The Hateful Eight 2015). Together, these films offered a specifically “Tarantinian” rendering of history: rewriting, manipulating and, for some, unethically deploying history for aesthetic effect. With regard to Django Unchained, this article examines how Tarantino’s historical revisionism provides a valuable point of inquiry into the ways in which “history” is depicted on-screen and, more importantly, how depictions of “the past” can prove useful for highlighting underlying contradictions, ambivalences and ambiguities in the “present”. Drawing upon Slavoj Žižek’s Lacanian approach to film analysis, it is argued that through a combination of fantasy, subversion and counterfactual possibility – most notable in the film’s final stand-off between its leading black characters – Tarantino is able to render the Real of U.S. slavery as an ahistorical antagonism. This antagonism highlights the ongoing trauma of these events in the present as well as the use of fantasy to explore their traumatic subject matter. Such historical fictions are not fixed to the past but, via an encounter with the Real, can be used to appraise the present

Anachronism of hope: the ‘to-come’ in post-horizonal times. In: Hirst, A., Houseman, T., Duque-Estrada, P.C., Edkins, J., and Mendes, C., Disobeying Marx, Disobeying Derrida—Hopes & Risks: A Forum on Jacques Derrida’s Specters of Marx after 25 Years, Part II

Jacques Derrida delivered the basis of The Specters of Marx: The State of the Debt, the Work of Mourning, & the New International as a plenary address at the conference ‘Whither Marxism?’ hosted by the University of California, Riverside, in 1993. The longer book version was published in French the same year and appeared in English and Portuguese the following year. In the decade after the publication of Specters, Derrida’s analyses provoked a large critical literature and invited both consternation and celebration by figures such as Antonio Negri, Wendy Brown and Frederic Jameson. This forum seeks to stimulate new reflections on Derrida, deconstruction and Specters of Marx by considering how the futures past announced by the book have fared after an eventful quarter century. In this group of contributions, Aggie Hirst and Tom Houseman, Paulo Cesar Duque-Estrada, Jenny Edkins and Cristiano Mendes reflect on the legacies of Marx and Derrida: on whether Derrida emphasized the wrong Marxian heritage, on the promise and risks of hauntology, on the ghostly potential for justice amidst devastation, and on the paradox of deconstruction’s legacy itself

Meta-analysis of genome-wide association studies identifies novel loci that influence cupping and the glaucomatous process

Glaucoma is characterized by irreversible optic nerve degeneration and is the most frequent cause of irreversible blindness worldwide. Here, the International Glaucoma Genetics Consortium conducts a meta-analysis of genome-wide association studies of vertical cup-disc ratio (VCDR), an important disease-related optic nerve parameter. In 21,094 individuals of European ancestry and 6,784 individuals of Asian ancestry, we identify 10 new loci associated with variation in VCDR. In a separate risk-score analysis of five case-control studies, Caucasians in the highest quintile have a 2.5-fold increased risk of primary open-angle glaucoma as compared with those in the lowest quintile. This study has more than doubled the known loci associated with optic disc cupping and will allow greater understanding of mechanisms involved in this common blinding condition

The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer

Abstract: Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM−/− patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors