Cullin-5 (Cul5) coordinates assembly of cullin-RING-E3 ubiquitin (Ub) ligase (CRL) complexes that include Suppressor of Cytokine Signaling (SOCS)-box-containing proteins. The SOCS-box proteins function to recruit specific substrates to the complex for ubiquitination and degradation. In hematopoiesis, SOCS-box proteins are best known for regulating the actions of cytokines that utilize the JAK-STAT signaling pathway.
View Article and Find Full Text PDFIntroduction: The cause of most CHD is unknown and considered complex, implicating genetic and environmental factors in disease causation. The Kids Heart BioBank was established in 2003 to accelerate genetic investigations into CHD.
Methods: Recruitment includes patients undergoing interventions for CHD at The Children's Hospital at Westmead.
Aims: The question of how to handle clinically actionable outcomes from retrospective research studies is poorly explored. In neuropathology, this problem is exacerbated by ongoing refinement in tumour classification. We sought to establish a disclosure threshold for potential revised diagnoses as determined by the neuro-oncology speciality.
View Article and Find Full Text PDFCell commitment to tumourigenesis and the onset of uncontrolled growth are critical determinants in cancer development but the early events directing tumour initiating cell (TIC) fate remain unclear. We reveal a single-cell transcriptome profile of brain TICs transitioning into tumour growth using the brain tumour (brat) neural stem cell-based Drosophila model. Prominent changes in metabolic and proteostasis-associated processes including ribogenesis are identified.
View Article and Find Full Text PDFMeningiomas are the most common intracranial brain tumours. These tumours are heterogeneous and encompass a wide spectrum of clinical aggressivity. Treatment options are limited to surgery and radiotherapy and have a risk of post-operative morbidities and radiation neurotoxicity, reflecting the need for new therapies.
View Article and Find Full Text PDFThe consequences of sub-lethal levels of ambient air pollution are underestimated for insects, for example, the accumulation of particulate matter on sensory receptors located on their antennae may have detrimental effects to their function. Here we show that the density of particulate matter on the antennae of houseflies (Musca domestica) collected from an urban environment increases with the severity of air pollution. A combination of behavioural assays, electroantennograms and transcriptomic analysis provide consistent evidence that a brief exposure to particulate matter pollution compromises olfactory perception of reproductive and food odours in both male and female houseflies.
View Article and Find Full Text PDFJ Phys Condens Matter
April 2023
We use terahertz time-domain spectroscopy to study gallium arsenide two-dimensional electron gas samples in external magnetic field. We measure cyclotron decay as a function of temperature from 0.4 to10Kand a quantum confinement dependence of the cyclotron decay time belowT0=1.
View Article and Find Full Text PDFGenetic referral for Lynch syndrome (LS) exemplifies complex clinical pathways. Identifying target behaviours (TBs) for change and associated barriers requires structured group consultation activities with busy clinicians - consolidating implementation activities whilst retaining rigour is crucial. This study aimed to: i) use process mapping to gain in-depth understandings of site-specific LS testing and referral practices in Australian hospitals and support identification of TBs for change, ii) explore if barriers to identified TBs could be identified through process mapping focus-group data, and iii) demonstrate pandemic-induced transition from in-person to virtual group interactive process mapping methods.
View Article and Find Full Text PDFThe metal-to-insulator phase transition (MIT) in low-dimensional materials and particularly two-dimensional layered semiconductors is exciting to explore due to the fact that it challenges the prediction that a two-dimensional system must be insulating at low temperatures. Thus, the exploration of MITs in 2D layered semiconductors expands the understanding of the underlying physics. Here we report the MIT of a few-layered MoSe field effect transistor under a gate bias (electric field) applied perpendicular to the MoSe layers.
View Article and Find Full Text PDFDuring embryogenesis, haematopoietic and endothelial lineages emerge closely in time and space. It is thought that the first blood and endothelium derive from a common clonal ancestor, the haemangioblast. However, investigation of candidate haemangioblasts in vitro revealed the capacity for mesenchymal differentiation, a feature more compatible with an earlier mesodermal precursor.
View Article and Find Full Text PDFDespite documented disparities with regard to treatment of skin of color (SOC) among dermatology trainees, a consensus has not yet been established as to how to improve trainee experiences with regard to SOC pathology. Our study objective was to systematically review the literature and assess interventions that have been implemented thus far to increase trainee competence and/or confidence in assessing SOC pathology. A systematic review of PubMed, Scopus, and Science Direct in January 2022 was performed, yielding a total of 1097 records.
View Article and Find Full Text PDFCutaneous squamous cell carcinoma (SCC) is the second most common type of skin cancer and accounts for approximately 25% of nonmelanoma skin cancers (NMSC). Although the majority of cutaneous SCC lesions have been treated successfully by surgical excision, cryotherapy, electrodessication, or Mohs micrographic surgery, some locally advanced SCC patients are either inoperable, have been metastasized, or both. In such patients, treatment is more challenging due to limited options.
View Article and Find Full Text PDFSocial interaction is one of the most important things that humans do on a day-to-day basis, impacting both mental and physical wellness. College is a particularly important period where social interaction becomes increasingly important as well as complex. While there is no currently agreed upon cognitive basis of social interaction, the executive function (EF) system is believed to play a central role.
View Article and Find Full Text PDFThe process of epigenetic silencing, while fundamentally important, is not yet completely understood. Here we report a replenishable female mouse embryonic stem cell (mESC) system, Xmas, that allows rapid assessment of X chromosome inactivation (XCI), the epigenetic silencing mechanism of one of the two X chromosomes that enables dosage compensation in female mammals. Through a targeted genetic screen in differentiating Xmas mESCs, we reveal that the BAF complex is required to create nucleosome-depleted regions at promoters on the inactive X chromosome during the earliest stages of establishment of XCI.
View Article and Find Full Text PDFDuring continent–continent collision, does the downgoing continental plate underplate far inboard of the collisional boundary or does it subduct steeply into the mantle, and how is this geometry manifested in the mantle flow field? We test conflicting models for these questions for Earth’s archetypal continental collision forming the Himalaya and Tibetan Plateau. Air-corrected helium isotope data (3He/4He) from 225 geothermal springs (196 from our group, 29 from the literature) delineate a boundary separating a Himalayan domain of only crustal helium from a Tibetan domain with significant mantle helium. This 1,000-km-long boundary is located close to the Yarlung-Zangbo Suture (YZS) in southern Tibet from 80 to 92°E and is interpreted to overlie the “mantle suture” where cold underplated Indian lithosphere is juxtaposed at >80 km depth against a sub-Tibetan incipiently molten asthenospheric mantle wedge.
View Article and Find Full Text PDFMagnetic field- and polarization-dependent measurements on bright and dark excitons in monolayer WSe combined with time-dependent density functional theory calculations reveal intriguing phenomena. Magnetic fields up to 25 T parallel to the WSe plane lead to a partial brightening of the energetically lower lying exciton, leading to an increase of the dephasing time. Using a broadband femtosecond pulse excitation, the bright and partially allowed excitonic state can be excited simultaneously, resulting in coherent quantum beating between these states.
View Article and Find Full Text PDFDeficiency of the tumor suppressor Merlin causes development of schwannoma, meningioma, and ependymoma tumors, which can occur spontaneously or in the hereditary disease neurofibromatosis type 2 (NF2). Merlin mutations are also relevant in a variety of other tumors. Surgery and radiotherapy are current first-line treatments; however, tumors frequently recur with limited treatment options.
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