On distribution formulas for complex and ℓ\ell-adic polylogarithms

We study an $\ell$-adic Galois analogue of the distribution formulas for polylogarithms with special emphasis on path dependency and arithmetic behaviors. As a goal, we obtain a notion of certain universal Kummer-Heisenberg measures that enable interpolating the $\ell$-adic polylogarithmic distribution relations for all degrees.Comment: This article has appeared in the proceedings volume "Periods in Quantum Field Theory and Arithmetic" (J.~Burgos Gil, K.~Ebrahimi-Fard, H.~Gangl eds), [Conference proceedings ICMAT-MZV 2014] Springer Proceedings in Mathematics \& Statistics {\bf 314} (2020), pp.593--61

Isotopic niche overlap between sympatric Australian snubfin and humpback dolphins

Ecological niche theory predicts the coexistence of closely related species is promoted by resource partitioning in space and time. Australian snubfin (Orcaella heinsohni) and humpback (Sousa sahulensis) dolphins live in sympatry throughout most of their range in northern Australian waters. We compared stable isotope ratios of carbon (δ13C) and nitrogen (δ15N) in their skin to investigate resource partitioning between these ecologically similar species. Skin samples were collected from live Australian snubfin (n = 31) and humpback dolphins (n = 23) along the east coast of Queensland in 2014–2015. Both species had similar δ13C and δ15N values and high (>50%) isotopic niche space overlap, suggesting that they feed at similar trophic levels, have substantial dietary overlap, and rely on similar basal food resources. Despite similarities, snubfin dolphins were more likely to have a larger δ15N value than humpback dolphins, indicating they may forage on a wider diversity of prey. Humpback dolphins were more likely to have a larger δ13C range suggesting they may forage on a wider range of habitats. Overall, results suggest that subtle differences in habitat use and prey selection are likely the principal resource partitioning mechanisms enabling the coexistence of Australian snubfin and humpback dolphins

Dromen over eeuwig leven. Vluchten voor de dood in een geseculariseerde samenleving

Inleiding. In de week na 30 oktober 2010, de dag waarop Harry Mulisch op 83-jarige leeftijd overleed, kolkten de thema’s dood en onsterfelijkheid door de Nederlandse media. Meestal was de toonzetting serieus, maar soms ook luchtiger, zoals toen Jeroen Brouwers over Mulisch’ adagium ‘Ik ben onsterfelijk tot het tegendeel bewezen is’ opmerkte dat ‘je (…) niet eleganter je middelvinger naar het universum (kunt) opsteken’. Soms was zij zelfs ronduit humoristisch, zoals in de grap volgens welke Mulisch, na door God zelf te zijn rondgeleid door de hemel, te kennen zou hebben gegeven ‘het boek toch beter te vinden’. Hoewel aandacht voor de thema’s van dood en onsterfelijkheid bij het overlijden van een van Nederlands grootste naoorlogse schrijvers natuurlijk op zichzelf niet opzienbarend is, illustreert zij hoezeer deze thema’s de ingrijpende processen van ontkerkelijking van de afgelopen halve eeuw hebben overleefd...

Transforming bonds: ritualising post-mortem relationships in the Netherlands

People continue relationships with their dead in a variety of ways. Since the 1990s, the idea of ‘continuing bonds’ has provided a framework for exploring and understanding post-mortem relationships. However, the dynamics of the bonds between the living and the dead have received little attention. By looking at the intersection of things, practices and spaces, this paper demonstrates that expressions of continuing bonds do not always point to continuity, and indeed can signify discontinuity. It explores the ‘transforming bonds’ between the recently bereaved and their deceased in the Netherlands, illustrating how post-mortem relationships change and how such changes affect the social location of the deceased and the bereaved. By attending to the ritual dynamics of separation, transition and integration, two aspects of the social and material relationships between the living and the dead are highlighted. First, attention is given to the ways wherein the bereaved relocate their deceased through material objects within and outside of their homes, enabling them to renegotiate the absence–presence of the deceased. Second, the paper illustrates that personalised incorporation practices are inevitably linked to negotiations and contestations in the social sphere, and the norms and values of the social environment

Quantitative methods to monitor RNA biomarkers in myotonic dystrophy

Myotonic dystrophy type 1 (DM1) and type 2 (DM2) are human neuromuscular disorders associated with mutations of simple repetitive sequences in afected genes. The abnormal expansion of CTG repeats in the 3?-UTR of the DMPK gene elicits DM1, whereas elongated CCTG repeats in intron 1 of ZNF9/CNBP triggers DM2. Pathogenesis of both disorders is manifested by nuclear retention of expanded repeat containing RNAs and aberrant alternative splicing. The precise determination of absolute numbers of mutant RNA molecules is important for a better understanding of disease complexity and for accurate evaluation of the efficacy of therapeutic drugs. We present two quantitative methods, Multiplex Ligation-Dependent Probe Amplifcation and droplet digital PCR, for studying the mutant DMPK transcript (DMPKexpRNA) and the aberrant alternative splicing in DM1 and DM2 human tissues and cells. We demonstrate that in DM1, the DMPKexpRNA is detected in higher copy number than its normal counterpart. Moreover, the absolute number of the mutant transcript indicates its low abundance with only a few copies per cell in DM1 fibroblasts. Most importantly, in conjunction with fuorescence in-situ hybridization experiments, our results suggest that in DM1 fibroblasts, the vast majority of nuclear RNA foci consist of a few molecules of DMPKexpRNA

The Chaperone ClpX Stimulates Expression of Staphylococcus aureus Protein A by Rot Dependent and Independent Pathways

The Clp ATPases (Hsp100) constitute a family of closely related proteins that have protein reactivating and remodelling activities typical of molecular chaperones. In Staphylococcus aureus the ClpX chaperone is essential for virulence and for transcription of spa encoding Protein A. The present study was undertaken to elucidate the mechanism by which ClpX stimulates expression of Protein A. For this purpose, we prepared antibodies directed against Rot, an activator of spa transcription, and demonstrated that cells devoid of ClpX contain three-fold less Rot than wild-type cells. By varying Rot expression from an inducible promoter we showed that expression of Protein A requires a threshold level of Rot. In the absence of ClpX the Rot content is reduced below this threshold level, hence, explaining the substantially reduced Protein A expression in the clpX mutant. Experiments addressed at pinpointing the role of ClpX in Rot synthesis revealed that ClpX is required for translation of Rot. Interestingly, translation of the spa mRNA was, like the rot mRNA, enhanced by ClpX. These data demonstrate that ClpX performs dual roles in regulating Protein A expression, as ClpX stimulates transcription of spa by enhancing translation of Rot, and that ClpX additionally is required for full translation of the spa mRNA. The current findings emphasize that ClpX has a central role in fine-tuning virulence regulation in S. aureus

Abortive Autophagy Induces Endoplasmic Reticulum Stress and Cell Death in Cancer Cells

Autophagic cell death or abortive autophagy has been proposed to eliminate damaged as well as cancer cells, but there remains a critical gap in our knowledge in how this process is regulated. The goal of this study was to identify modulators of the autophagic cell death pathway and elucidate their effects on cellular signaling and function. The result of our siRNA library screenings show that an intact coatomer complex I (COPI) is obligatory for productive autophagy. Depletion of COPI complex members decreased cell survival and impaired productive autophagy which preceded endoplasmic reticulum stress. Further, abortive autophagy provoked by COPI depletion significantly altered growth factor signaling in multiple cancer cell lines. Finally, we show that COPI complex members are overexpressed in an array of cancer cell lines and several types of cancer tissues as compared to normal cell lines or tissues. In cancer tissues, overexpression of COPI members is associated with poor prognosis. Our results demonstrate that the coatomer complex is essential for productive autophagy and cellular survival, and thus inhibition of COPI members may promote cell death of cancer cells when apoptosis is compromised

Targeting the hypoxic fraction of tumours using hypoxia activated prodrugs

The presence of a microenvironment within most tumours containing regions of low oxygen tension or hypoxia has profound biological and therapeutic implications. Tumour hypoxia is known to promote the development of an aggressive phenotype, resistance to both chemotherapy and radiotherapy and is strongly associated with poor clinical outcome. Paradoxically, it is recognised as a high priority target and one therapeutic strategies designed to eradicate hypoxic cells in tumours are a group of compounds known collectively as hypoxia activated prodrugs (HAPs) or bioreductive drugs. These drugs are inactive prodrugs that require enzymatic activation (typically by 1 or 2 electron oxidoreductases) to generate cytotoxic species with selectivity for hypoxic cells being determined by (i) the ability of oxygen to either reverse or inhibit the activation process and (ii) the presence of elevated expression of oxidoreductases in tumours. The concepts underpinning HAP development were established over 40 years ago and have been refined over the years to produce a new generation of HAPs that are under preclinical and clinical development. The purpose of this article is to describe current progress in the development of HAPs focusing on the mechanisms of action, preclinical properties and clinical progress of leading examples