Ferrites are an essential material in modern industry due to their exceptional magnetic properties and high resistivity. Many applications of ferrites necessitate exposure to high energy electrons, particularly space science and particle accelerators, where charging, multipacting, and electron clouds (ECs) are major issues. ECs are of particular concern around the Ni/Zn soft ferrite kicker magnets as the large hadron collider (LHC) undergoes its high luminosity upgrade.
View Article and Find Full Text PDFApoptotic cell death is regulated by the BCL-2 protein family, with clusters of BAK or BAX homodimers driving pore formation in the mitochondrial outer membrane via a poorly understood process. There is growing evidence that, in addition to BAK and BAX, lipids play an important role in pore formation. Towards a better understanding of the lipidic drivers of apoptotic pore formation in isolated mitochondria, two complementary approaches were taken.
View Article and Find Full Text PDFComparative microplastic (MP) data for cephalopods between oceans is scarce. Our aim was to quantify, characterise, and compare MPs in gills, digestive gland, and mantle of chokka squid from the South Atlantic Ocean (SAO) and Indian Ocean (IO) off the coast of South Africa. South African squid had more MPs compared with other studies (means = 2.
View Article and Find Full Text PDFThe B-cell lymphoma 2 (BCL2) family members, BCL2-associated protein X (BAX) and BCL2 homologous antagonist killer (BAK), are required for programmed cell death via the mitochondrial pathway. When cells are stressed, damaged or redundant, the balance of power between the BCL2 family of proteins shifts towards BAX and BAK, allowing their transition from an inactive, monomeric state to a membrane-active oligomeric form that releases cytochrome c from the mitochondrial intermembrane space. That oligomeric state has an essential intermediate, a symmetric homodimer of BAX or BAK.
View Article and Find Full Text PDFWe investigated elemental concentrations in muscle tissue of three species of dolphins incidentally bycaught off the KwaZulu-Natal coastline, South Africa. Thirty-six major, minor and trace elements were analysed in Indian Ocean humpback dolphin Sousa plumbea (n = 36), Indo-Pacific bottlenose dolphin Tursiops aduncus (n = 32) and the Common dolphin Delphinus delphis (n = 8). Significant differences in concentration between the three species were observed for 11 elements (cadmium, iron, manganese, sodium, platinum, antimony, selenium, strontium, uranium, vanadium and zinc).
View Article and Find Full Text PDFBackground: The clinical significance of sentinel nodes (SNs) in the triangular intermuscular space (TIS) of patients with melanoma is poorly understood. This study aimed to determine their incidence and positivity rate, and to report their management and patient outcomes.
Methods: This was a single-institution retrospective cohort study of patients with unilateral or bilateral TIS SNs on lymphoscintigraphy treated between 1992 and 2017.
Despite their common use in research, monoclonal antibodies are currently not systematically sequenced. This can lead to issues with reproducibility and the occasional loss of antibodies with loss of cell lines. Hybridoma cell lines have been the primary means of generating monoclonal antibodies from immunized animals, including mice, rats, rabbits, and alpacas.
View Article and Find Full Text PDFThe intrinsic apoptosis pathway, regulated by the BCL-2 protein family, is essential for embryonic development. Using mice lacking all known apoptosis effectors, BAX, BAK and BOK, we have previously defined the processes during development that require apoptosis. Rare Bok Bax Bak triple knockout (TKO) mice developed to adulthood and several tissues that were thought to require apoptosis during development appeared normal.
View Article and Find Full Text PDFA body of data supports the existence of core (α2-α5) dimers of BAK and BAX in the oligomeric, membrane-perturbing conformation of these essential apoptotic effector molecules. Molecular structures for these dimers have only been captured for truncated constructs encompassing the core domain alone. Here, we report a crystal structure of BAK α2-α8 dimers (i.
View Article and Find Full Text PDFBackground: In-transit metastases (ITMs) are cutaneous or subcutaneous regional metastases that may occur in patients with melanoma. ITMs are often multiple and new lesions tend to appear over time. Ultrasonography can detect impalpable subcutaneous tumors.
View Article and Find Full Text PDFBackground: Two recent publications have reported that a shorter interval between preoperative lymphoscintigraphy and sentinel node biopsy (SNB) is associated with improved survival of patients with primary cutaneous melanoma. The aims of this study were to analyse prospectively collected survival data for patients who had SNB on the same day as lymphoscintigraphy or the day after; and to assess tracer migration from sentinel nodes to second-tier nodes after lymphoscintigraphy on the previous day.
Methods: Outcome data were obtained for patients who had lymphoscintigraphy and SNB on the same day (time interval less than 8 h) or the next day (interval more than 16 h).
Halogenated natural products (HNPs) and persistent organic pollutants (POPs) were quantified in South African sardines () from one site in the South Atlantic Ocean and one in the Indian Ocean. At both sites, HNPs [2,3,3',4,4',5,5'-heptachloro-1'-methyl-1,2'-bipyrrole (Q1), mixed halogenated compound 1 (MHC-1), 2,4,6-tribromoanisole (2,4,6-TBA), 2'-MeO-BDE 68 (BC-2), and 6-MeO-BDE 47 (BC-3)] were 1 order of magnitude higher concentrated than anthropogenic POPs [mainly polychlorinated biphenyls (PCBs) and dichlorodiphenyltrichloroethane (DDT), ∼3 ng/g lipids]. MHC-1 and Q1 were the major HNPs in the samples from both sites, contributing with up to 49 and 52 ng/g lipids, respectively.
View Article and Find Full Text PDFBAK and BAX, which drive commitment to apoptosis, are activated principally by certain BH3-only proteins that bind them and trigger major rearrangements. One crucial conformation change is exposure of their BH3 domain which allows BAK or BAX to form homodimers, and potentially to autoactivate other BAK and BAX molecules to ensure robust pore formation and cell death. Here, we test whether full-length BAK or mitochondrial BAX that are specifically activated by antibodies can then activate other BAK or BAX molecules.
View Article and Find Full Text PDFBackground: The results of the DeCOG-SLT and MSLT-II studies, published in 2016 and mid-2017, indicated no survival benefit from completion lymph node dissection (CLND) in melanoma patients with positive sentinel nodes (SNs). Subsequently, several studies have been published reporting a benefit of adjuvant systemic therapy in patients with stage III melanoma. The current study assessed how these findings influenced management of SN-positive patients in a dedicated melanoma treatment centre.
View Article and Find Full Text PDFBackground: Sentinel node (SN) biopsy (SNB) is not routinely performed for melanoma patients with local recurrence (LR) or in-transit metastasis (ITM). This study aimed to describe the technique, findings, and prognostic value of this procedure, and the outcome for such patients at our institution.
Methods: Prospectively collected data were obtained from the Melanoma Institute Australia database.
Background: Sentinel node (SN) biopsy (SNB) has become standard of care in clinically localized melanoma patients. Although it is minimally invasive, advanced age and/or comorbidities may render SNB inadvisable in some patients. Focused ultrasound follow-up of SNs identified by preoperative lymphoscintigraphy may be an alternative in these patients.
View Article and Find Full Text PDFObjective: To assess whether preoperative ultrasound (US) assessment of regional lymph nodes in patients who present with primary cutaneous melanoma provides accurate staging.
Background: It has been suggested that preoperative US could avoid the need for sentinel node (SN) biopsy, but in most single-institution reports, the sensitivity of preoperative US has been low.
Methods: Preoperative US data and SNB results were analyzed for patients enrolled at 20 centers participating in the screening phase of the second Multicenter Selective Lymphadenectomy Trial.
Background And Purpose: Patients with a primary melanoma below the knee may have lymphatic drainage to a sentinel node (SN) in the popliteal fossa. The purpose of this study was to analyze lymphatic drainage to this site and to describe clinical features and surgical management of SNs in the popliteal fossa.
Methods: Patients with a primary melanoma below the knee presenting to Melanoma Institute Australia between 1992 and 2013 were analyzed.
Mitochondrial permeabilization is a key event in the intrinsic pathway of apoptosis, and is mediated by either of the BCL-2 family members BAK or BAX. These two proteins generate pores in the mitochondrial outer membrane that release factors such as cytochrome c into the cytosol to trigger caspase activation and apoptotic cell death. To generate pores, BAK and BAX undergo major changes including BAX translocation to the outer membrane, and partial unfolding, dimerization, and oligomerization.
View Article and Find Full Text PDFPhilos Trans R Soc Lond B Biol Sci
August 2017
Apoptotic cell death via the mitochondrial pathway occurs in all vertebrate cells and requires the formation of pores in the mitochondrial outer membrane. Two Bcl-2 protein family members, Bak and Bax, form these pores during apoptosis, and how they do so has been investigated for the last two decades. Many of the conformation changes that occur during their transition to pore-forming proteins have now been delineated.
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