Textile technology in Nepal in the 5th-7th centuries CE: the case of Samdzong

The first results of textile and dye analyses of cloth remains recovered in Samdzong, Upper Mustang, Nepal, are presented. The site consists of ten shaft tombs, dated between the 400-650 CE, cut into a high cliff face at an elevation of 4000 m asl. The dry climate and high altitude favoured the exceptional preservation of organic materials. One of the objects recovered from the elite Samdzong 5 tomb complex is composed of wool fabrics to which copper, glass and cloth beads are attached and probably constitutes the remains of a complex decorative headwear, which may have been attached to a gold/silver mask. SEM was used to identify the fibre sources of the textiles, which are all of animal nature. Two of the textiles are made of degummed silk. There is no evidence for local silk production suggesting that Samdzong was inserted into the long-distance trade network of the Silk Road. HPLC-DAD analysis permitted identification of a variety of organic dyes, including Indian lac, munjeet, turmeric and knotweed/indigo, while cinnabar was identified through micro Raman spectrometry. The results indicate that locally produced materials were used in combination with those likely imported from afar, including China and India.The research leading to these results has received funding from the European Research Council under the European Union's Seventh Framework Programme (FP/2007-2013-312603). Excavations at Samdzong have been supported by grants to Aldenderfer from the National Geographic Society and the Henry Luce Foundation. Many thanks to Alexia Coudray and Marie-Christine Maquoi for their dedicated work in the KIK/IRPA laboratory.This is the final version of the article. It first appeared from Taylor & Francis via http://dx.doi.org/10.1080/20548923.2015.111042

Ceramic production in the Kur River Basin (Fars, Iran) during the middle to late second millennium bce: a geochemical and technological characterization.

A total of 119 middle to late second millennium bce pottery samples from six sites in the Kur River Basin (Fars, Iran) were examined to characterize these ceramics and reconstruct their manufacturing technology and the origin of the primary materials. For this, a combined study of handheld XRF and thin‐section petrography was performed. The geochemical signatures of these ceramics were defined and interpreted in their archaeological and geological framework, resulting in the determination of different production processes and clay types used for four ceramic wares (Middle Elamite, Qaleh, Shogha and Taimuran) and the identification of possible outcrops used for Shogha–Taimuran production

The North Sea Benthos Project: planning, management and objectives

The ICES Benthos Ecology Working Group is integrating recent macrobenthic infaunal data (1999-2001) available from various sources, including national monitoring surveys, in North Sea soft bottom sediments. lt is expected to cover most of the North Sea. The main goal is an overall comparison with the North Sea Benthos Survey data of 1986, in order to determine whether there have been any significant changes and, if so, what may be the causal influences (e.g., climate change, fishing impacts). The work will contribute valuable information on several other topics such as habitat classification and the distribution of endangered species. Therefore, in addition to physico-chemical measurements of sediments samples alongside the benthic fauna, information on water depths, temperature, water quality and salinity will be incorporated in the analysis of species and community distributions. Also, we will use existing ecological and hydrographical models for currents, bottom shear stress and carbon input, along with information on the distribution of habitat types, to explain the observed distribution patterns. At the ASC, an overview of the data available will be presented as well as the anticipated outcomes, and the first steps taken to deal with taxonomic differences and other issues affecting the capability to integrate submitted information

Triad3a induces the degradation of early necrosome to limit RipK1-dependent cytokine production and necroptosis.

Understanding the molecular signaling in programmed cell death is vital to a practical understanding of inflammation and immune cell function. Here we identify a previously unrecognized mechanism that functions to downregulate the necrosome, a central signaling complex involved in inflammation and necroptosis. We show that RipK1 associates with RipK3 in an early necrosome, independent of RipK3 phosphorylation and MLKL-induced necroptotic death. We find that formation of the early necrosome activates K48-ubiquitin-dependent proteasomal degradation of RipK1, Caspase-8, and other necrosomal proteins. Our results reveal that the E3-ubiquitin ligase Triad3a promotes this negative feedback loop independently of typical RipK1 ubiquitin editing enzymes, cIAPs, A20, or CYLD. Finally, we show that Triad3a-dependent necrosomal degradation limits necroptosis and production of inflammatory cytokines. These results reveal a new mechanism of shutting off necrosome signaling and may pave the way to new strategies for therapeutic manipulation of inflammatory responses

Essential versus accessory aspects of cell death: recommendations of the NCCD 2015

Cells exposed to extreme physicochemical or mechanical stimuli die in an uncontrollable manner, as a result of their immediate structural breakdown. Such an unavoidable variant of cellular demise is generally referred to as ‘accidental cell death’ (ACD). In most settings, however, cell death is initiated by a genetically encoded apparatus, correlating with the fact that its course can be altered by pharmacologic or genetic interventions. ‘Regulated cell death’ (RCD) can occur as part of physiologic programs or can be activated once adaptive responses to perturbations of the extracellular or intracellular microenvironment fail. The biochemical phenomena that accompany RCD may be harnessed to classify it into a few subtypes, which often (but not always) exhibit stereotyped morphologic features. Nonetheless, efficiently inhibiting the processes that are commonly thought to cause RCD, such as the activation of executioner caspases in the course of apoptosis, does not exert true cytoprotective effects in the mammalian system, but simply alters the kinetics of cellular demise as it shifts its morphologic and biochemical correlates. Conversely, bona fide cytoprotection can be achieved by inhibiting the transduction of lethal signals in the early phases of the process, when adaptive responses are still operational. Thus, the mechanisms that truly execute RCD may be less understood, less inhibitable and perhaps more homogeneous than previously thought. Here, the Nomenclature Committee on Cell Death formulates a set of recommendations to help scientists and researchers to discriminate between essential and accessory aspects of cell death

A time predefined variable depth search for nurse rostering

This paper presents a variable depth search for the nurse rostering problem. The algorithm works by chaining together single neighbourhood swaps into more effective compound moves. It achieves this by using heuristics to decide whether to continue extending a chain and which candidates to examine as the next potential link in the chain. Because end users vary in how long they are willing to wait for solutions, a particular goal of this research was to create an algorithm that accepts a user specified computational time limit and uses it effectively. When compared against previously published approaches the results show that the algorithm is very competitive

Underwater Leidenfrost nanochemistry for creation of size-tailored zinc peroxide cancer nanotherapeutics

The dynamic underwater chemistry seen in nature is inspiring for the next generation of eco-friendly nanochemistry. In this context, green synthesis of size-tailored nanoparticles in a facile and scalable manner via a dynamic process is an interesting challenge. Simulating the volcano-induced dynamic chemistry of the deep ocean, here we demonstrate the Leidenfrost dynamic chemistry occurring in an underwater overheated confined zone as a new tool for customized creation of nanoclusters of zinc peroxide. The hydrodynamic nature of the phenomenon ensures eruption of the nanoclusters towards a much colder region, giving rise to growth of monodisperse, size-tailored nanoclusters. Such nanoparticles are investigated in terms of their cytotoxicity on suspension and adherent cells to prove their applicability as cancer nanotherapeutics. Our research can pave the way for employment of the dynamic green nanochemistry in facile, scalable fabrication of size-tailored nanoparticles for biomedical applications.Peer reviewe

Similar NF-κB Gene Signatures in TNF-α Treated Human Endothelial Cells and Breast Tumor Biopsies

BACKGROUND: Endothelial dysfunction has been implicated in the pathogenesis of diverse pathologies ranging from vascular and immune diseases to cancer. TNF-α is one of the mediators of endothelial dysfunction through the activation of transcription factors, including NF-κB. While HUVEC (macrovascular cells) have been largely used in the past, here, we documented an NF-κB gene signature in TNFα-stimulated microvascular endothelial cells HMEC often used in tumor angiogenesis studies. METHODOLOGY/PRINCIPAL FINDINGS: We measured mRNA expression of 55 NF-κB related genes using quantitative RT-PCR in HUVEC and HMEC. Our study identified twenty genes markedly up-regulated in response to TNFα, including adhesion molecules, cytokines, chemokines, and apoptosis regulators, some of them being identified as TNF-α-inducible genes for the first time in endothelial cells (two apoptosis regulators, TNFAIP3 and TNFRSF10B/Trail R2 (DR5), the chemokines GM-CSF/CSF2 and MCF/CSF1, and CD40 and TNF-α itself, as well as NF-κB components (RELB, NFKB1 or 50/p105 and NFKB2 or p52/p100). For eight genes, the fold induction was much higher in HMEC, as compared to HUVEC. Most importantly, our study described for the first time a connection between NF-κB activation and the induction of most, if not all, of these genes in HMEC as evaluated by pharmacological inhibition and RelA expression knock-down by RNA interference. Moreover, since TNF-α is highly expressed in tumors, we further applied the NF-κB gene signature documented in TNFα-stimulated endothelial cells to human breast tumors. We found a significant positive correlation between TNF and the majority (85 %) of the identified endothelial TNF-induced genes in a well-defined series of 96 (48 ERα positive and 48 ERα negative) breast tumors. CONCLUSION/SIGNIFICANCE: Taken together these data suggest the potential use of this NF-κB gene signature in analyzing the role of TNF-α in the endothelial dysfunction, as well as in breast tumors independently of the presence of ERα

The Anticancer Plant Triterpenoid, Avicin D, Regulates Glucocorticoid Receptor Signaling: Implications for Cellular Metabolism

Avicins, a family of apoptotic triterpene electrophiles, are known to regulate cellular metabolism and energy homeostasis, by targeting the mitochondria. Having evolved from “ancient hopanoids,” avicins bear a structural resemblance with glucocorticoids (GCs), which are the endogenous regulators of metabolism and energy balance. These structural and functional similarities prompted us to compare the mode of action of avicin D with dexamethasone (Dex), a prototypical GC. Using cold competition assay, we show that Avicin D competes with Dex for binding to the GC receptor (GR), leading to its nuclear translocation. In contrast to Dex, avicin-induced nuclear translocation of GR does not result in transcriptional activation of GC-dependent genes. Instead we observe a decrease in the expression of GC-dependent metabolic proteins such as PEPCK and FASN. However, like Dex, avicin D treatment does induce a transrepressive effect on the pro-inflammatory transcription factor NF-κB. While avicin's ability to inhibit NF-κB and its downstream targets appear to be GR-dependent, its pro-apoptotic effects were independent of GR expression. Using various deletion mutants of GR, we demonstrate the requirement of both the DNA and ligand binding domains of GR in mediating avicin D's transrepressive effects. Modeling of avicin-GR interaction revealed that avicin molecule binds only to the antagonist confirmation of GR. These findings suggest that avicin D has properties of being a selective GR modulator that separates transactivation from transrepression. Since the gene-activating properties of GR are mainly linked to its metabolic effects, and the negative interference with the activity of transcription factors to its anti-inflammatory and immune suppressive effects, the identification of such a dissociated GR ligand could have great potential for therapeutic use