Helter skelter, topsy-turvy and ‘loonycolour’: carnivalesque realism in 'Saturday Night and Sunday Morning'

Saturday Night and Sunday Morning has been reductively sidelined as “working class realism” where that term implies a mere reportage of grim reality. Such a view ignores the joyously subversive spirit alive in the novel. This essay argues that the “glorious loonycolour” of Arthur Seaton’s internal world has a transformative effect on external reality. Through Arthur’s consciousness, the pubs and fairgrounds of 1950s working class culture become a transgressive, carnivalesque site of inversion, an energetic, death-defying topsy-turveydom. Sillitoe, then, does violence to realism and allows us, if only temporarily, to see reality in a different, and radically optimistic, way. At the same time, his version of the carnivalesque is less romanticised than Mikhail Bakhtin’s, since he is alive to the dangers of containment which lurk at its heart. This awareness climaxes in Arthur’s move towards matrimony, an institution which may contain his vitality or provide a new outlet

Confronting the abject: women and dead babies in modern English fiction

Jean Rhys and Aldous Huxley were groundbreaking in that they represented the experience of illegal abortion openly with no apparent disapprobation, drawing it to the attention of a significant readership. Their representations – bodily, but grim – resonate with Bakhtin’s argument that modernity can sustain only a denigrated version of the grotesque, a faint echo of the carnivalesque humour of Rabelais, where laughter is superseded by fear (in Kristeva’s term, the abject). Twenty-five years later, Alan Sillitoe and Nell Dunn pushed the limits further, placing abortion at the centre of their novels, forcing the reader to engage with the woman’s experience, while working within a realist tradition that did not spare harsh details. Within this tradition they are nonetheless sometimes playful, even comic, in their language and modes of representation, carrying readers far beyond the stark specifics of realism and outside the reductive restrictions of the polarized abortion debate

Mammalian phosphatidylinositol 4-kinases as modulators of membrane trafficking and lipid signaling networks.

The four mammalian phosphatidylinositol 4-kinases modulate inter-organelle lipid trafficking, phosphoinositide signalling and intracellular vesicle trafficking. In addition to catalytic domains required for the synthesis of PI4P, the phosphatidylinositol 4-kinases also contain isoform-specific structural motifs that mediate interactions with proteins such as AP-3 and the E3 ubiquitin ligase Itch, and such structural differences determine isoform-specific roles in membrane trafficking. Moreover, different permutations of phosphatidylinositol 4-kinase isozymes may be required for a single cellular function such as occurs during distinct stages of GPCR signalling and in Golgi to lysosome trafficking. Phosphatidylinositol 4-kinases have recently been implicated in human disease. Emerging paradigms include increased phosphatidylinositol 4-kinase expression in some cancers, impaired functioning associated with neurological pathologies, the subversion of PI4P trafficking functions in bacterial infection and the activation of lipid kinase activity in viral disease. We discuss how the diverse and sometimes overlapping functions of the phosphatidylinositol 4-kinases present challenges for the design of isoform-specific inhibitors in a therapeutic context

Phosphatidylinositol 4-kinase IIβ negatively regulates invadopodia formation and suppresses an invasive cellular phenotype

The type II PI 4-kinases enzymes synthesise the lipid phosphatidylinositol 4-phosphate (PI(4)P) which has been detected at the Golgi complex and endosomal compartments, and which recruits clathrin adaptors. Despite common mechanistic similarities between the isoforms, the extent of their redundancy is unclear.We found that depletion of PI4KIIα and PI4KIIβ using siRNA led to actin remodelling. Depletion of PI4KIIβ also induced the formation of invadopodia containing membrane type I matrix metalloproteinase (MT1-MMP).Depletion of PI4KII isoforms also differentially affected TGN pools of PI(4)P and post-TGN traffic. PI4KIIβ depletion caused increased MT1-MMP trafficking to invasive structures at the plasma membrane and was accompanied by reduced colocalisation of MT1-MMP with membranes containing the endosomal markers Rab5 and Rab7, but increased localisation with the exocytic Rab8. Depletion of PI4KIIβ was sufficient to confer an aggressive invasive phenotype on minimally invasive HeLa and MCF-7 cell lines. Mining oncogenomic databases revealed that loss of the PI4K2B allele and underexpression of PI4KIIβ mRNA is associated with human cancers. This finding supports the cell data and suggests that PI4KIIβ may be a clinically significant suppressor of invasion. We propose that PI4KIIβ synthesises a pool of PI(4)P that maintains MT1-MMP traffic in the degradative pathway and suppresses the formation of invadopodia

The endogenous subcellular localisations of the long chain fatty acid-activating enzymes ACSL3 and ACSL4 in sarcoma and breast cancer cells

Fatty acid uptake and metabolism are often dysregulated in cancer cells. Fatty acid activation is a critical step that allows these biomolecules to enter cellular metabolic pathways such as mitochondrial β-oxidation for ATP generation or the lipogenic routes that generate bioactive lipids such as the inositol phospholipids. Fatty acid activation by the addition of coenzyme A is catalysed by a family of enzymes called the acyl CoA synthetase ligases (ACSL). Furthermore, enhanced expression of particular ACSL isoforms, such as ACSL4, is a feature of some more aggressive cancers and may contribute to the oncogenic phenotype. This study focuses on ACSL3 and ACSL4, closely related structural homologues that preferentially activate palmitate and arachidonate fatty acids, respectively. In this study, immunohistochemical screening of multiple soft tissue tumour arrays revealed that ACSL3 and ACSL4 were highly, but differentially, expressed in a subset of leiomyosarcomas, fibrosarcomas and rhabdomyosarcomas, with consistent cytoplasmic and granular stainings of tumour cells. The intracellular localisations of endogenously expressed ACSL3 and ACSL4 were further investigated by detailed subcellular fractionation analyses of HT1080 fibrosarcoma and MCF-7 breast cancer cells. ACSL3 distribution closely overlapped with proteins involved in trafficking from the trans-Golgi network and endosomes. In contrast, the ACSL4 localisation pattern more closely followed that of calnexin which is an endoplasmic reticulum resident chaperone. Confocal immunofluorescence imaging of MCF-7 cells confirmed the intracellular localisations of both enzymes. These observations reveal new information regarding the compartmentation of fatty acid metabolism in cancer cells

Bottlenose Dolphins Mom-Calf Interactions over the First and Second Year of Life

As both wild and captive dolphin calves develop, they spend less time with their mothers and more time engaged in independent activities. In this study, the social development of six captive dolphin calves (Tursiops truncatus) were examined over the first and second year of life. Focal animal behavioral ethogram data were collected using a 30 second scan sampling technique. The predominant swim position and individual behaviors were recorded. There were a number of general developmental patterns: (1) an increase in the percentage of time that the calves engaged in solo swimming, (2) a decrease in infant position, and (3) a decrease in echelon position. The shift in primary swim position and increase in independent (solitary) behaviors exhibited over the study is consistent with past research on calf development. The basis for the difference each calf’s behavior could be a result of the experience or type of mother, the unique personalities in the calves, or a combination of both

Beluga Whales Socio-Sexual Interactions and Behaviors (Delphinapterus leucas)

Cetaceans are known for developing social relationships with each other by displaying various social and contact behaviors. Few studies have investigated the social interactions and types of contact behavior between belugas (Delphinapterus leucas). The present study focused on the frequencies of many social behaviors observed among four belugas (three males and one female) in the care of humans and the changes in behavior over an extended period of time. Continuous data were collection via video recordings over a four year period and were coded for social interactions. Preliminary analysis revealed that Male C was the most likely to initiate social interactions in this social group. It appears that the social interactions among the individuals may be somewhat stable over time. The findings of this study have implications for better understanding beluga social interactions of whales that are living under managed care

Differential effects of the phosphatidylinositol 4-kinases, PI4KII alpha and PI4KIII beta, on Akt activation and apoptosis

In this study, we investigated the role of PI4P synthesis by the phosphatidylinositol 4-kinases, PI4KII alpha and PI4KIII beta, in epidermal growth factor (EGF)-stimulated phosphoinositide signaling and cell survival. In COS-7 cells, knockdown of either isozyme by RNA interference reduced basal levels of PI4P and PI(4,5)P-2, without affecting receptor activation. Only knockdown of PI4KII alpha inhibited EGF-stimulated Akt phosphorylation, indicating that decreased PI(4,5)P-2 synthesis observed by loss of either isoform could not account for this PI4KII alpha-specific effect. Phospholipase Cc activation was also differentially affected by knockdown of either PI4K isozyme. Overexpression of kinase-inactive PI4KII alpha, which induces defective endosomal trafficking without reducing PI(4,5)P-2 levels, also reduced Akt activation. Furthermore, PI4KII alpha knockdown profoundly inhibited cell proliferation and induced apoptosis as evidenced by the cleavage of caspase-3 and its substrate poly(ADP-ribose) polymerase. However, in MDA-MB-231 breast cancer cells, apoptosis was observed subsequent to knockdown of either PI4KII alpha or PI4KIII beta and this correlated with enhanced proapoptotic Akt phosphorylation. The differential effects of phosphatidylinositol 4-kinase knockdown in the two cell lines lead to the conclusion that phosphoinositide turnover is inhibited through PI4P substrate depletion, whereas impaired antiapoptotic Akt signaling is an indirect consequence of dysfunctional endosomal trafficking

The Politics of Service Delivery Reform

This article identifies the leaders, the supporters and the resisters of public service reform. It adopts a principal–agent framework, comparing reality with an ‘ideal’ situation in which citizens are the principals over political policy-makers as their agents, and policy-makers are the principals over public service officials as their agents. Reform in most developing countries is complicated by an additional set of external actors — international financial institutions and donors. In practice, international agencies and core government officials usually act as the ‘principals’ in the determination of reforms. The analysis identifies the interests involved in reform, indicating how the balance between them is affected by institutional and sectoral factors. Organizational reforms, particularly in the social sectors, present greater difficulties than first generation economic policy reforms