Attention, Music, Dance: Embodying the “Cinema of Attractions”

In this essay I take up the question of whether the “cinema of attractions,” as identified and analyzed by film scholars Tom Gunning and André Gaudreault, might be a useful tool for critical analysis not only of early silent film, its exhibitionist aesthetics, and approach to spectatorship, but of theatrical dance from the period. Certainly, as for its general historical currency, the “cinema of attractions” is thought to encode the culture of modernity from which it arose: the visual spectacle, sensory fascination, bodily engagement, mechanical rhythm, violent juxtapositions, and new experiences of time and space available within the modern urban environment. Moreover, that cinema relied in no small part on dance itself: as a performing art, dance was central to the “attractions” industry, prime raw material starring The Body in Motion, a favorite fascination of contemporary art and popular entertainment. My aim is to push the analogy further, suggesting how cinema and theatrical dance might cue a similar mode of attention: that is, despite the former’s reliance on the camera, its reproductive aesthetic and industrial mechanicity, and the latter’s live theatrical aspect. Indeed, in the latter, I argue, music can be analogized to the camera itself, helping determine and sustain a particular attention economy, while pointing to itself—just as filmed objects stare at the camera—as artifice or contrivance.

Towards the Synthesis of Hybrid Peloruside A and Laulimalide Analogues

<p>(+)-Peloruside A is a novel cytotoxic marine natural product isolated from the New Zealand sponge Mycale hentscheli(42). Peloruside A is a potential anticancer agent that has a similar mode of action to that of the successful drug paclitaxel. Biological analysis indicated that (+)-peloruside A promotes tubulin hyperassembly and cellular microtubule stabilisation which lead to mitosis blockage in the G2/M phase of the cell cycle and consequent cell apoptosis(43),(47). (-)-Laulimalide is also a cytotoxic natural product with microtubule stabilising bioactivity, and is a potential anticancer agent(47). Biological analysis showed that (+)-peloruside A and (-)-laulimalide are competitive, suggesting that they bind to the same active site(47). (+)-Peloruside A and (-)-laulimalide also display synergy with taxoids(47). Due to the structural complexity of peloruside A, our research has focused on developing an analogue 151 for ease of synthesis. Thus, the simplified C5-C9 dihydropyran moiety of (-)-laulimalide, with fewer stereocentres than that of (+)-peloruside A, has been incorporated into analogue 151 whilst retaining the 16- membered ring backbone of (+)-peloruside A. The proposed synthesis of 151 involves a Yamaguchi macrolactonization, a 1,5-anti-aldol coupling, and a ring closing metathesis as key reactions. This thesis reports on the synthesis of key fragments of analogue 151 and the crucial 1,5-anti-aldol coupling reaction for the assembly of the carbon backbone.</p>

Towards the Synthesis of Hybrid Peloruside A and Laulimalide Analogues

<p>(+)-Peloruside A is a novel cytotoxic marine natural product isolated from the New Zealand sponge Mycale hentscheli(42). Peloruside A is a potential anticancer agent that has a similar mode of action to that of the successful drug paclitaxel. Biological analysis indicated that (+)-peloruside A promotes tubulin hyperassembly and cellular microtubule stabilisation which lead to mitosis blockage in the G2/M phase of the cell cycle and consequent cell apoptosis(43),(47). (-)-Laulimalide is also a cytotoxic natural product with microtubule stabilising bioactivity, and is a potential anticancer agent(47). Biological analysis showed that (+)-peloruside A and (-)-laulimalide are competitive, suggesting that they bind to the same active site(47). (+)-Peloruside A and (-)-laulimalide also display synergy with taxoids(47). Due to the structural complexity of peloruside A, our research has focused on developing an analogue 151 for ease of synthesis. Thus, the simplified C5-C9 dihydropyran moiety of (-)-laulimalide, with fewer stereocentres than that of (+)-peloruside A, has been incorporated into analogue 151 whilst retaining the 16- membered ring backbone of (+)-peloruside A. The proposed synthesis of 151 involves a Yamaguchi macrolactonization, a 1,5-anti-aldol coupling, and a ring closing metathesis as key reactions. This thesis reports on the synthesis of key fragments of analogue 151 and the crucial 1,5-anti-aldol coupling reaction for the assembly of the carbon backbone.</p>

Ayurvedic Management of Congenital Elongation of Cervix- A Single Case Study

Elongation is one among the various congenital abnormalities of cervix, which is often one of the causes of primary infertility. The only available treatment is cervical amputation. The word yoni collectively refers to reproductive organs, however here it can be considered as the cervix. So elongated cervix can be correlated to Prasramsini Yoni Vyapat where there is laxity and descend of the cervix. All Acharyas have mentioned similar mode of treatment in case of Srasta Yoni which include Abhyanga, Sweda, Veshavara Bandha, Uttarabasti etc. A case report of patient presenting with congenital cervical elongation is being discussed here. In this case there was reduction in the elongation of the cervix by Veshavara Bandha and Uttarabasti with Jathyadi Taila. The drugs used in Veshavara Bandha were having Balya, Brimhana and Grahi properties which helped in reducing the length of the cervix significantly and preventing further elongation. Thus Ayurvedic management was found to be effective in elongation of cervix to an extent even though it cannot be cured completely.

Structures of a deAMPylation complex rationalise the switch between antagonistic catalytic activities of FICD

The endoplasmic reticulum (ER) Hsp70 chaperone BiP is regulated by AMPylation, a reversible inactivating post-translational modification. Both BiP AMPylation and deAMPylation are catalysed by a single ER-localised enzyme, FICD. Here we present crystallographic and solution structures of a deAMPylation Michaelis complex formed between mammalian AMPylated BiP and FICD. The latter, via its tetratricopeptide repeat domain, binds a surface that is specific to ATP-state Hsp70 chaperones, explaining the exquisite selectivity of FICD for BiP’s ATP-bound conformation both when AMPylating and deAMPylating Thr518. The eukaryotic deAMPylation mechanism thus revealed, rationalises the role of the conserved Fic domain Glu234 as a gatekeeper residue that both inhibits AMPylation and facilitates hydrolytic deAMPylation catalysed by dimeric FICD. These findings point to a monomerisation-induced increase in Glu234 flexibility as the basis of an oligomeric state-dependent switch between FICD’s antagonistic activities, despite a similar mode of engagement of its two substrates — unmodified and AMPylated BiP.

Integrated Analysis of lncRNA and mRNA in Subcutaneous Adipose Tissue of Ningxiang Pig

Ningxiang pigs, a Chinese bred pig known for its tender meat and high quality unsaturated fatty acids. This study discovers the transcription profiles and functional networks in long non-coding RNA (lncRNA) and messenger RNA (mRNA) in subcutaneous adipose tissue. Subcutaneous adipose tissue was collected from piglet, nursery pig, early fattening, and late fattening stage of Ningxiang piglets, and lncRNA and mRNA transcription of each stage was profiled. A total of 339,204,926 (piglet), 315,609,246 (nursery), 266,798,202 (early fattening), and 343,740,308 (late fattening) clean reads were generated, and 2872 novel lncRNAs were identified. Additionally, 10,084 differential mRNAs (DEmRNAs) and 931 differential lncRNAs were determined. Most DEmRNAs were up-regulated in the piglet stage, while they were down-regulated in late fattening stage. A complicated interaction between mRNAs and lncRNAs was identified via STEM and WGCNA, demonstrated that lncRNAs are a significant regulatory component in mRNAs. The findings showed that modules 2 and 5 have a similar mode of transcription for both mRNA and lncRNA, and were mainly participated in steroid biosynthesis, glycosphingolipid biosynthesis, metabolic pathways, and glycerolipid metabolism. The mRNAs and lncRNAs transcription levels of both modules was higher in the early and late fattening stage, which may be due to the active activity of the metabolism in relation to fatty acids, sterols, steroids, and lipids in the subcutaneous adipose tissue during the early and late fattening stage. These findings could be expected to result in further research of the functional properties of lncRNA from subcutaneous adipose tissue at different stages of development in Ningxiang pigs.

A Galantamine–Curcumin Hybrid Decreases the Cytotoxicity of Amyloid-Beta Peptide on SH-SY5Y Cells

Misfolded amyloid beta (Aβ) peptides aggregate and form neurotoxic oligomers. Membrane and mitochondrial damages, calcium dysregulation, oxidative stress, and fibril deposits are among the possible mechanisms of Aβ cytotoxicity. Galantamine (GAL) prevents apoptosis induced by Aβ mainly through the ability to stimulate allosterically the α7 nAChRs and to regulate the calcium cytosolic concentration. Here, we examined the cytoprotective effects of two GAL derivatives, namely compounds 4b and 8, against Aβ cytotoxicity on the human neuroblastoma cell line SH-SY5Y. The protective effects were tested at simultaneous administration, pre-incubation and post-incubation, with Aβ. GAL and curcumin (CU) were used in the study as reference compounds. It was found that 4b protects cells in a similar mode as GAL, while compound 8 and CU potentiate the toxic effects of Aβ. Allosteric stimulation of α7 nAChRs is suggested as a possible mechanism of the cytoprotectivity of 4b. These and previous findings characterize 4b as a prospective non-toxic multi-target agent against neurodegenerative disorders with inhibitory activity on acetylcholinesterase, antioxidant, and cytoprotective properties.

Developmental Exposure to Endocrine Disrupting Chemicals and Its Impact on Cardio-Metabolic-Renal Health

Developmental origin of health and disease postulates that the footprints of early life exposure are followed as an endowment of risk for adult diseases. Epidemiological and experimental evidence suggest that an adverse fetal environment can affect the health of offspring throughout their lifetime. Exposure to endocrine disrupting chemicals (EDCs) during fetal development can affect the hormone system homeostasis, resulting in a broad spectrum of adverse health outcomes. In the present review, we have described the effect of prenatal EDCs exposure on cardio-metabolic-renal health, using the available epidemiological and experimental evidence. We also discuss the potential mechanisms of their action, which include epigenetic changes, hormonal imprinting, loss of energy homeostasis, and metabolic perturbations. The effect of prenatal EDCs exposure on cardio-metabolic-renal health, which is a complex condition of an altered biological landscape, can be further examined in the case of other environmental stressors with a similar mode of action.

Assessing Combined Effects for Mixtures of Similar and Dissimilar Acting Neuroactive Substances on Zebrafish Embryo Movement

Risk assessment of chemicals is usually conducted for individual chemicals whereas mixtures of chemicals occur in the environment. Considering that neuroactive chemicals are a group of contaminants that dominate the environment, it is then imperative to understand the combined effects of mixtures. The commonly used models to predict mixture effects, namely concentration addition (CA) and independent action (IA), are thought to be suitable for mixtures of similarly or dissimilarly acting components, respectively. For mixture toxicity prediction, one important challenge is to clarify whether to group neuroactive substances based on similar mechanisms of action, e.g., same molecular target or rather similar toxicological response, e.g., hyper- or hypoactivity (effect direction). We addressed this by using the spontaneous tail coiling (STC) of zebrafish embryos, which represents the earliest observable motor activity in the developing neural network, as a model to elucidate the link between the mechanism of action and toxicological response. Our objective was to answer the following two questions: (1) Can the mixture models CA or IA be used to predict combined effects for neuroactive chemical mixtures when the components share a similar mode of action (i.e., hyper- or hypoactivity) but show different mechanism of action? (2) Will a mixture of chemicals where the components show opposing effect directions result in an antagonistic combined effect? Results indicate that mixture toxicity of chemicals such as propafenone and abamectin as well as chlorpyrifos and hexaconazole that are known to show different mechanisms of action but similar effect directions were predictable using CA and IA models. This could be interpreted with the convergence of effects on the neural level leading to either a collective activation or inhibition of synapses. We also found antagonistic effects for mixtures containing substances with opposing effect direction. Finally, we discuss how the STC may be used to amend risk assessment.

Structures of a deAMPylation complex rationalise the switch between antagonistic catalytic activities of FICD

The endoplasmic reticulum (ER) Hsp70 chaperone BiP is regulated by AMPylation, a reversible inactivating post-translational modification. Both BiP AMPylation and deAMPylation are catalysed by a single ER-localised enzyme, FICD. Here we present long-sought crystallographic and solution structures of a deAMPylation Michaelis complex formed between mammalian AMPylated BiP and FICD. The latter, via its tetratricopeptide repeat domain, binds a surface that is specific to ATP-state Hsp70 chaperones, explaining the exquisite selectivity of FICD for BiP's ATP-bound conformation both when AMPylating and deAMPylating Thr518. The eukaryotic deAMPylation mechanism thus revealed, rationalises the role of the conserved Fic domain Glu234 as a gatekeeper residue that both inhibits AMPylation and facilitates hydrolytic deAMPylation catalysed by dimeric FICD. These findings point to a monomerisation-induced increase in Glu234 flexibility as the basis of an oligomeric state-dependent switch between FICD's antagonistic activities, despite a similar mode of engagement of its two substrates - unmodified and AMPylated BiP.