'Remembering to forget': public secrecy and memory of sexual violence in the Bangladesh war of 1971

This article explores the processes through which the 'public secrecy' of rape during the Bangladesh war of 1971 operates within the present-day ethnographic context. It examines contemporary commemorations of the war and of women who have achieved local and national fame as rape victims (euphemistically referred to as 'war heroines'). The article analyses the discrepancy between raped women's national position as icons of 'honour' and their local reception through sanctions and constant khota (sarcastic/censorious remarks expressing scorn and evoking the unpleasant events). By exploring the relationship between scorn, honour, rape, sexuality, narratives of remembrance, and the emergence of 'public secrets'– and how these are interwoven by the subjectivity of the raped – the article argues that memories of rape are simultaneously located within the ambiguities of revelation and of concealment which are indispensable to the operations of power. In the process the article establishes the relationship between secrecy and memory. Further, a focus on the intersubjective domain of memory provides methodological and ethical tools with which to engage with narratives of the past relating to wartime violence.     

An anti-infective peptide that selectively modulates the innate immune response

We show that an innate defense-regulator peptide (IDR-1) was protective in mouse models of infection with important Gram-positive and Gram-negative pathogens, including methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus and Salmonella enterica serovar Typhimurium. When given from 48 h before to 6 h after infection, the peptide was effective by both local and systemic administration. Because protection by IDR-1 was prevented by in vivo depletion of monocytes and macrophages, but not neutrophils or B- and T-lymphocytes, we conclude that monocytes and macrophages are key effector cells. IDR-1 was not directly antimicrobial: gene and protein expression analysis in human and mouse monocytes and macrophages indicated that IDR-1, acting through mitogen-activated protein kinase and other signaling pathways, enhanced the levels of monocyte chemokines while reducing pro-inflammatory cytokine responses. To our knowledge, an innate defense regulator that counters infection by selective modulation of innate immunity without obvious toxicities has not been reported previously.     

Nucleic acids exert a sequence-independent cooperative effect on sequence-dependent activation of Toll-like receptor 9

Toll-like receptor 9 (TLR9) activates the innate immune system in response to microbial DNA or mimicking oligodeoxynucleotides. Although cell stimulation experiments demonstrate the preferential activation of TLR9 by CpG-containing nucleic acids, direct binding investigations have reached contradictory conclusions with respect to the ability of this receptor to bind nucleic acids in a sequence-specific manner. To address this apparent discrepancy, we report the purification of the soluble ectodomain of human TLR9 with characterization of its ligand binding properties. We observe that TLR9 has a high degree of specificity in its ability to bind nucleic acids that contain CpG dinucleotides as well as higher order motifs that mediate species-specific activation. However, TLR9 is also functionally influenced by nucleic acids in a sequence-independent fashion as both stimulatory and nonstimulatory nucleic acids sensitize TLR9 for in vitro ligand binding as well as in vivo activation. We propose a model in which receptor activation is achieved in a sequence-dependent manner, and sensitivity is modulated by the absolute concentration of nucleic acids in a sequence-independent fashion. This model bears resemblance to that recently proposed for Toll in that activation is a two-step process in which formation of a ligand-bound monomer precedes formation of the activated dimer. In each model receptor sensitivity is determined within the second step with the crucial distinction that Toll undergoes negative cooperativity, whereas TLR9 is sensitized through a positive cooperative effect.     

From virgin education to real education

The now famous virgin headspace experiment from late Braja D. Mookherjee and Subha Patel, and its use in the creation of scent 'Virgin No 1' by Christophe Laudamiel and Christoph Hornetz for the novel by Patrick Süskind, and the movie by Tom Tykwer 'Perfume--The Story of a Murderer' (Constantin Film-Thierry Mugler Parfums-IFF, 2006) is discussed. Another fragrance from the luxury coffret, 'Salon Rouge', is described as well, illustrating how molecules and natural ingredients can be utilized, not only to create innovative or artistic fragrance compositions, but also to provide fundamental consumer education, improving the public image both of Chemistry and Perfumery.     

N-substituted pyrrolidines and tetrahydrofurans as novel AMPAR positive modulators

A series of novel AMPA receptor positive modulators displaying CNS penetration have been discovered with sub-micromolar activity and good selectivity over the cardiac channel receptor, hERG. We describe here the synthesis of these compounds which are biaryl pyrrolidine and tetrahydrofuran sulfonamides and disclose their activities against the human GluA2 flip isoform homotetrameric receptor.     

Vitamin D in a Northern Canadian First Nation Population: Dietary Intake,Serum Concentrations and Functional Gene Polymorphisms

The wide spectrum of vitamin D activity has focused attention on its potential role in the elevated burden of disease in a northern Canadian First Nations (Dené) cohort. Vitamin D insufficiency, and gene polymorphisms in the vitamin D receptor (VDR) and vitamin D binding protein (VDBP) have been implicated in susceptibility to infectious and chronic diseases. The objectives of this study were to determine the contribution of vitamin D from food, and measure the serum concentrations of 25-hydroxyvitamin D₃ (25-OHD₃) and VDBP in Dené participants. Single nucleotide polymorphisms (SNPs) associated with the dysregulation of the innate immune response were typed and counted. Potential correlations between the SNPs and serum concentrations of 25-OHD₃ and VDBP were evaluated. Venous blood was collected in summer and winter over a one-year period and analyzed for 25-OHD₃ and VDBP concentrations (N = 46). A questionnaire was administered to determine the amount of dietary vitamin D consumed. Sixty-one percent and 30% of the participants had 25-OHD₃ serum concentrations <75 nmol/L in the winter and summer respectively. Mean vitamin D binding protein concentrations were within the normal range in the winter but below normal in the summer. VDBP and VDR gene polymorphisms affect the bioavailability and regulation of 25-OHD₃. The Dené had a high frequency of the VDBP D432E-G allele (71%) and the Gc1 genotype (90%), associated with high concentrations of VDBP and a high binding affinity to 25-OHD₃. The Dené had a high frequency of VDR Fok1-f allele (82%), which has been associated with a down-regulated Th1 immune response. VDBP and VDR polymorphisms, and low winter 25-OHD₃ serum concentrations may be risk factors for infectious diseases and chronic conditions related to the dysregulation of the vitamin D pathway.     

In vivo activity of an azole series of CCR2 antagonists

Optimisation of a series of biaryl sulphonamides resulted in the identification of compound 7 which demonstrated dose-dependent and strain-specific inhibition of monocyte recruitment in a thioglycollate-induced peritonitis model of inflammation.     

Identification of a sulfonamide series of CCR2 antagonists

A series of sulfonamide CCR2 antagonists was identified by high-throughput screening. Management of molecular weight and physical properties, in particular moderation of lipophilicity and study of pK_a, yielded highly potent CCR2 antagonists exhibiting good pharmacokinetic properties and improved potency in the presence of human plasma.     

The discovery of a series of N-substituted 3-(4-piperidinyl)-1,3-benzoxazolinones and oxindoles as highly brain penetrant,selective muscarinic M1 agonists

A series of N-substituted 3-(4-piperidinyl)-1,3-benzoxazolinones and oxindoles are reported which were found to be potent and selective muscarinic M₁ agonists. By control of the physicochemical characteristics of the series, particularly the lipophilicity, compounds with good metabolic stability and excellent brain penetration were identified. An exemplar of the series was shown to be pro-cognitive in the novel object recognition rat model of temporal induced memory deficit.     

Modulation of interleukin-1β-induced inflammatory responses by a synthetic cationic innate defence regulator peptide, IDR-1002, in synovial fibroblasts

Introduction  

Innate defence regulator (IDR) peptides are synthetic cationic peptides, variants of naturally occurring innate immune effector molecules known as host defence peptides. IDR peptides were recently demonstrated to limit infection-associated inflammation selectively without compromising host innate immune functions. This study examined the impact of a 12-amino acid IDR peptide, IDR-1002, in pro-inflammatory cytokine interleukin (IL)-1β-induced responses in synovial fibroblasts, a critical cell type in the pathogenesis of inflammatory arthritis.