Unravelling the stratigraphy and sedimentation history of the uppermost Cretaceous to Eocene sediments of the Kuching Zone in West Sarawak (Malaysia), Borneo

The Kuching Zone in West Sarawak consists of two different sedimentary basins, the Kayan and Ketungau Basins. The sedimentary successions in the basins are part of the Kuching Supergroup that extends into Kalimantan. The uppermost Cretaceous (Maastrichtian) to Lower Eocene Kayan Group forms the sedimentary deposits directly above a major unconformity, the Pedawan Unconformity, which marks the cessation of subduction-related magmatism beneath SW Borneo and the Schwaner Mountains, due to termination of the Paleo-Pacific subduction. The successions consist of the Kayan and Penrissen Sandstones and are dominated by fluvial channels, alluvial fans and floodplain deposits with some deltaic to tidally-influenced sections in the Kayan Sandstone. In the late Early or early Middle Eocene, sedimentation in this basin ceased and a new basin, the Ketungau Basin, developed to the east. This change is marked by the Kayan Unconformity. Sedimentation resumed in the Middle Eocene (Lutetian) with the marginal marine, tidal to deltaic Ngili Sandstone and Silantek Formation. Upsequence, the Silantek Formation is dominated by floodplain and subsidiary fluvial deposits. The Bako-Mintu Sandstone, a potential lateral equivalent of the Silantek Formation, is formed of major fluvial channels. The top of the Ketungau Group in West Sarawak is formed by the fluvially-dominated Tutoop Sandstone. This shows a transition of the Ketungau Group in time towards terrestrial/fluvially-dominated deposits. Paleocurrent measurements show river systems were complex, but reveal a dominant southern source. This suggests uplift of southern Borneo initiated in the region of the present-day Schwaner Mountains from the latest Cretaceous onwards. Additional sources were local sources in the West Borneo province, Mesozoic melanges to the east and potentially the Malay Peninsula. The Ketungau Group also includes reworked deposits of the Kayan Group. The sediments of the Kuching Supergroup are predominantly horizontal or dip with low angles and form large open synclines. Steep dips are usually restricted to faults, such as the Lupar Line

Strongholding the Synagogue to Stronghold the City: Urban-Religious Configurations in an Israeli Mixed-City

This article explores the geopolitical significance of public religious institutions and the ways in which it has corresponded to changes in their urban environment. Based on a spatial analysis and ethnography of urban synagogues in the northern Israeli mixed city of Acre that were established and constructed by communities of Jewish immigrants from North African countries, we demonstrate how significant shifts in the city's demographic pattern and landscape have affected these institutions' ascribed functions and meanings. We theorise this dynamic as ‘strongholding’, or, more specifically, strongholding the synagogue as a means of strongholding the city. The formation of the synagogue as a stronghold is enacted through a dual configuration process by which the religious legitimacy, which the synagogue bestows on those who maintain it, is interwoven into a broader urban sociopolitical struggle to claim a presence in the city

The roles of Hhex and Ikzf1 in murine NK cell biology

© 2018 Dr. Wilford Wei Qiang GohNatural killer (NK) cells are effector lymphocytes of the innate immune system that are known for their ability to kill transformed and virus-infected cells. NK cells originate from haematopoietic stem cells in the bone marrow and studies on mouse models have revealed that NK cell development is a complex and tightly regulated process. The development of NK cells can be broadly categorised into two phases: lineage commitment and maturation. Whilst the transcription factors Hhex and Ikzf1 have previously been implicated in NK cell lineage commitment, their importance in NK cell maturation has remained enigmatic until now. Using mouse models that have recently become available, the expression of these transcription factors was specifically inactivated in lineage-committed NK cells to determine the role of these transcription factors in maturing NK cells. The role of Hhex and Ikzf1 in NK cell effector function was also examined, since NK cell maturation is accompanied by the acquisition of cytotoxic functions. This study identifies Hhex and Ikzf1 as novel regulators of NK cell homeostasis, with the loss of either Hhex or Ikzf1 conferring defects in NK cell survival. Through comprehensive phenotyping and transcriptomic profiling, Hhex was determined to be required for NK cell survival by blocking accumulation of the pro-apoptotic factor BIM, while Ikzf1 promoted NK cell survival by maintaining IL-15 responsiveness. Overall, Ikzf1 appears to play a greater role in NK cell biology than Hhex, since Ikzf1-deficient NK cells presented additional anomalies in maturation and function. Interestingly, emerging data suggests that both transcription factors are required to maintain the appropriate rates of cell metabolism that underpins many aspects of NK cell biology. Finally, RNA-sequencing of Hhex- and Ikzf1-deficient NK cells has revealed new directions for future studies that will improve understanding of how these two transcription factors regulate NK cell biology

Regulation of Murine Natural Killer Cell Development

Natural killer (NK) cells are effector lymphocytes of the innate immune system that are known for their ability to kill transformed and virus-infected cells. NK cells originate from hematopoietic stem cells in the bone marrow, and studies on mouse models have revealed that NK cell development is a complex, yet tightly regulated process, which is dependent on both intrinsic and extrinsic factors. The development of NK cells can be broadly categorized into two phases: lineage commitment and maturation. Efforts to better define the developmental framework of NK cells have led to the identification of several murine NK progenitor populations and mature NK cell subsets, each defined by a varied set of cell surface markers. Nevertheless, the relationship between some of these NK cell subsets remains to be determined. The classical approach to studying both NK cell development and function is to identify the transcription factors involved and elucidate the mechanistic action of each transcription factor. In this regard, recent studies have provided further insight into the mechanisms by which transcription factors, such as ID2, FOXO1, Kruppel-like factor 2, and GATA-binding protein 3 regulate various aspects of NK cell biology. It is also becoming evident that the biology of NK cells is not only transcriptionally regulated but also determined by epigenetic alterations and posttranscriptional regulation of gene expression by microRNAs. This review summarizes recent progress made in NK development, focusing primarily on transcriptional regulators and their mechanistic actions

Generation of novel Id2 and E2-2, E2A and HEB antibodies reveals novel Id2 binding partners and species-specific expression of E-proteins in NK cells

NK cells are cytotoxic lymphocytes with a key role in limiting tumour metastases. In mice, the NK cell lineage continually expresses high levels of the Inhibitor of DNA-binding 2 (Id2) protein and loss of Id2 is incongruous with their survival due to aberrant E-protein target gene activity. Using novel Id2 and E-protein antibodies that detect both mouse and human proteins, we have extensively characterised Id2 and E-protein expression in murine and human NK cells. We detected clear expression of E2 A and HEB, and to a lesser extent E2-2 in murine NK cells. In contrast HEB appears to be the major E-protein expressed in human NK cells, with minor E2-2 expression and surprisingly, no E2 A detected in primary NK cells nor human NK cell lines. These novel antibodies are also functional in immunofluorescence and immunoprecipitation. Mass spectrometry analysis of Id2 immuno-precipitated from murine NK cells revealed a number of novel associated proteins including several members of the SWI/SNF-related matrix-associated actin-dependent regulator chromatin (SMARC) and Mediator complex (MED) families. Taken together, these data highlight the utility of novel Id2 and E-protein antibodies and caution against mouse models for understanding Id2/E-protein biology in NK cells given their clearly disparate expression patternbetween species

Recipient BCL2 inhibition and NK cell ablation form part of a reduced intensity conditioning regime that improves allo-bone marrow transplantation outcomes

Allogeneic hematopoietic stem cell transplantation (alloSCT) is used to treat over 15,000 patients with acute myeloid leukemia (AML) per year. Donor graft-versus-leukemia (GVL) effect can prevent AML relapse; however, alloSCT is limited by significant toxicity related to conditioning intensity, immunosuppression, opportunistic infections, and graft-versus-host disease (GVHD). Reducing the intensity of conditioning regimens prior to alloSCT has improved their tolerability, but does not alter the pattern of GVHD and has been associated with increased rates of graft rejection and relapse. Here, using a murine pre-clinical model, we describe a novel recipient conditioning approach combining reduced intensity conditioning with either genetic or pharmacological inhibition of NK cell numbers that permits efficient donor engraftment and promotes GVL without inducing GVHD. We show that NK cell-specific deletion of Bcl2 or Mcl1 in mice, or pharmacological inhibition of BCL2 impairs radio-resistant NK cell-mediated rejection of allogeneic engraftment and allows reduction of conditioning intensity below that associated with GVHD priming. The combination of reduced intensity conditioning and NK cell targeting in mice allowed successful donor T cell engraftment and protective immunity against AML while avoiding GVHD. These findings suggest that reduced conditioning in combination with targeted therapies against recipient NK cells may allow the delivery of effective alloSCT against AML while reducing the toxicities associated with more intensive conditioning including GVHD

“Up the Windsor Road” : social complexity, geographies of emotion, and the rise of Hillsong

This chapter explores the expansion of Hillsong in socio-historical terms, matching its responses to key challenges to contexts and trends in each of the following Hillsong 1.0–4.0 “identities”: as context driven local churchplant; as culture driven regional worship church; as personality-driven transnational network Church; and as brand-driven, technology-mediated Global Church. All these identities co-exist in various localities. The chapter plays particular attention to contextual factors such as Australian public secularism and crises of politics, corporatism and infrastructure, and the consequent development of geographies of emotion and aesthetics which help Hillsong “bridge” into global settings. It is a story not only of the ability of new evangelicalisms to renew and overplant old forms, but of remarkable internal resources of leadership and organization adaptability