Intracellular calcium links milk stasis to lysosome-dependent cell death during early mammary gland involution.

Involution of the mammary gland after lactation is a dramatic example of coordinated cell death. Weaning causes distension of the alveolar structures due to the accumulation of milk, which, in turn, activates STAT3 and initiates a caspase-independent but lysosome-dependent cell death (LDCD) pathway. Although the importance of STAT3 and LDCD in early mammary involution is well established, it has not been entirely clear how milk stasis activates STAT3.

Intracellular Calcium links Milk Stasis to Lysosome Dependent Cell Death by Activating a TGFβ3/TFEB/STAT3 Pathway Early during Mammary Gland Involution.

Involution of the mammary gland after lactation is a dramatic example of coordinated cell death. Weaning causes distension of the alveolar structures due to the accumulation of milk, which, in turn, activates STAT3 and initiates a caspase-independent but lysosome-dependent cell death (LDCD) pathway. Although the importance of STAT3 and LDCD in early mammary involution is well established, it has not been entirely clear how milk stasis activates STAT3.

A Case of Hypercalcemia from PTHrP-Producing Fibromyxoid Sarcoma Responsive to Glucocorticoid Therapy.

The treatment of parathyroid hormone-related protein (PTHrP)-mediated hypercalcemia of malignancy includes treating the malignancy, intravenous fluids, and anti-resorptive therapies such as zoledronic acid or denosumab. PTHrP-mediated hypercalcemia has been reported in benign conditions such as systemic lupus erythematous (SLE) and sarcoidosis and appears to be responsive to glucocorticoids. We report a case of PTHrP-induced hypercalcemia due to a malignancy-low grade fibromyxoid sarcoma-that responded to glucocorticoid treatment.

Unravelling the Diversity of Microorganisms in Ticks from Australian Wildlife.

Ticks and tick-borne pathogens pose a significant threat to the health and welfare of humans and animals. Our knowledge about pathogens carried by ticks of Australian wildlife is limited. This study aimed to characterise ticks and tick-borne microorganisms from a range of wildlife species across six sites in Victoria, Australia.

Environmental correlates of temporal variation in the prey species of Australian fur seals inferred from scat analysis.

Marine ecosystems in southeastern Australia are responding rapidly to climate change. We monitored the diet of the Australian fur seal (), a key marine predator, over 17 years (1998-2014) to examine temporal changes. Frequency of occurrence (FO) of prey was used as a proxy for ecosystem change.

Genomic insights into the secondary aquatic transition of penguins.

Penguins lost the ability to fly more than 60 million years ago, subsequently evolving a hyper-specialized marine body plan. Within the framework of a genome-scale, fossil-inclusive phylogeny, we identify key geological events that shaped penguin diversification and genomic signatures consistent with widespread refugia/recolonization during major climate oscillations. We further identify a suite of genes potentially underpinning adaptations related to thermoregulation, oxygenation, diving, vision, diet, immunity and body size, which might have facilitated their remarkable secondary transition to an aquatic ecology.

PTHrP induces STAT5 activation, secretory differentiation and accelerates mammary tumor development.

Background: Parathyroid hormone-related protein (PTHrP) is required for embryonic breast development and has important functions during lactation, when it is produced by alveolar epithelial cells and secreted into the maternal circulation to mobilize skeletal calcium used for milk production. PTHrP is also produced by breast cancers, and GWAS studies suggest that it influences breast cancer risk. However, the exact functions of PTHrP in breast cancer biology remain unsettled.

Hemispheric asymmetry in ocean change and the productivity of ecosystem sentinels.

Climate change and other human activities are causing profound effects on marine ecosystem productivity. We show that the breeding success of seabirds is tracking hemispheric differences in ocean warming and human impacts, with the strongest effects on fish-eating, surface-foraging species in the north. Hemispheric asymmetry suggests the need for ocean management at hemispheric scales.

Insulin-stimulated endoproteolytic TUG cleavage links energy expenditure with glucose uptake.

TUG tethering proteins bind and sequester GLUT4 glucose transporters intracellularly, and insulin stimulates TUG cleavage to translocate GLUT4 to the cell surface and increase glucose uptake. This effect of insulin is independent of phosphatidylinositol 3-kinase, and its physiological relevance remains uncertain. Here we show that this TUG cleavage pathway regulates both insulin-stimulated glucose uptake in muscle and organism-level energy expenditure.

Into the sea: Antimicrobial resistance determinants in the microbiota of little penguins (Eudyptula minor).

Terrestrial and aquatic birds have been proposed as sentinels for the spread of antimicrobial resistant bacteria, but few species have been investigated specifically in the context of AMR in the marine ecosystem. This study contrasts the occurrence of class 1 integrons and associated antimicrobial resistance genes in wild and captive little penguins (Eudyptula minor), an Australian seabird with local population declines. PCR screening of faecal samples (n = 448) revealed a significant difference in the prevalence of class 1 integrons in wild and captive groups, 3.

A physiological cost to behavioural tolerance.

Few studies of animal escape behaviour simultaneously investigate behavioural and physiological responses. Differences between these response types, however, have consequences for the way in which habituation or tolerance is interpreted - behavioural habituation may incur physiological costs. We simultaneously measured heart rate (HR) and behavioural responses during standardised approaches to incubating Masked Lapwings Vanellus miles, an urban-frequenting ground-nesting bird.

Myeloid-Derived Suppressor Cells in Nonmetastatic Urothelial Carcinoma of Bladder Is Associated With Pathologic Complete Response and Overall Survival.

Background: Myeloid-derived suppressor cells (MDSC) have immunosuppressive activity and enhance tumor progression. We hypothesized that lower blood MDSC would correlate with pathologic complete response and better outcomes in nonmetastatic urothelial carcinoma (UC).

Patients And Methods: Before cystectomy, blood MDSC were measured in whole blood (WB) and peripheral blood mononuclear cells using flow cytometry.

Trophic niches of a seabird assemblage in Bass Strait, south-eastern Australia.

The foraging niches of seabirds are driven by a variety of factors, including competition for prey that promotes divergence in trophic niches. Bass Strait, south-eastern Australia, is a key region for seabirds, with little penguins , short-tailed shearwaters , fairy prions and common diving-petrels being particularly abundant in the region. The trophic niches of these species were investigated using isotopic values in whole blood and by identifying prey remains in stomach contents.

High-coverage genomes to elucidate the evolution of penguins.

Background: Penguins (Sphenisciformes) are a remarkable order of flightless wing-propelled diving seabirds distributed widely across the southern hemisphere. They share a volant common ancestor with Procellariiformes close to the Cretaceous-Paleogene boundary (66 million years ago) and subsequently lost the ability to fly but enhanced their diving capabilities. With ∼20 species among 6 genera, penguins range from the tropical Galápagos Islands to the oceanic temperate forests of New Zealand, the rocky coastlines of the sub-Antarctic islands, and the sea ice around Antarctica.

Equitable Chick Survival in Three Species of the Non-Migratory Shorebird Despite Species-Specific Sexual Dimorphism of the Young.

Sex-biases in populations can have important implications for species' social biology, population demography and mating systems. It has recently been suggested that in some shorebirds, sex-specific bias in survival of precocial young may occur. This may be driven by variation in the brood sex-ratio and/or the sexual size dimorphism of young birds, which may influence predator escape capacity.

Cathepsin K-deficient osteocytes prevent lactation-induced bone loss and parathyroid hormone suppression.

Lactation induces bone loss to provide sufficient calcium in the milk, a process that involves osteoclastic bone resorption but also osteocytes and perilacunar resorption. The exact mechanisms by which osteocytes contribute to bone loss remain elusive. Osteocytes express genes required in osteoclasts for bone resorption, including cathepsin K (Ctsk), and lactation elevates their expression.

NHERF1 Is Required for Localization of PMCA2 and Suppression of Early Involution in the Female Lactating Mammary Gland.

Prior studies have demonstrated that the calcium pump, plasma membrane calcium ATPase 2 (PMCA2), mediates calcium transport into milk and prevents mammary epithelial cell death during lactation. PMCA2 also regulates cell proliferation and cell death in breast cancer cells, in part by maintaining the receptor tyrosine kinase ErbB2/HER2 within specialized plasma membrane domains. Furthermore, the regulation of PMCA2 membrane localization and activity in breast cancer cells requires its interaction with the PDZ domain-containing scaffolding molecule sodium-hydrogen exchanger regulatory factor (NHERF) 1.

Inhibition of ezrin causes PKCα-mediated internalization of erbb2/HER2 tyrosine kinase in breast cancer cells.

Unlike other ErbB family members, HER2 levels are maintained on the cell surface when the receptor is activated, allowing prolonged signaling and contributing to its transforming ability. Interactions between HER2, HSP90, PMCA2, and NHERF1 within specialized plasma membrane domains contribute to the membrane retention of HER2. We hypothesized that the scaffolding protein ezrin, which has been shown to interact with NHERF1, might also help stabilize the HER2-PMCA2-NHERF1 complex at the plasma membrane.

Myeloid-derived suppressors cells (MDSC) correlate with clinicopathologic factors and pathologic complete response (pCR) in patients with urothelial carcinoma (UC) undergoing cystectomy.

Background: Myeloid derived suppressor cells (MDSC) are heterogeneous immunosuppressive cells with potential predictive and prognostic roles in cancer. The association between MDSC, clinicopathologic factors, and pathologic response in patients with bladder urothelial carcinoma (UC) was explored.

Methods: Peripheral blood or tissue were collected from patients with UC undergoing definitive surgery.

Penguin colony attendance under artificial lights for ecotourism.

Wildlife watching is an emerging ecotourism activity around the world. In Australia and New Zealand, night viewing of little penguins attracts hundreds of thousands of visitors per year. As penguins start coming ashore after sunset, artificial lighting is essential to allow visitors to view them in the dark.

Microbiota of little penguins and short-tailed shearwaters during development.

The establishment and early colonisation of the gastrointestinal (GI) tract has been recognised as a crucial stage in chick development, with pioneering microbial species responsible for influencing the development of the GI tract and influencing host health, fitness and disease status throughout life. Development of the microbiota in long lived seabirds is poorly understood. This study characterised the microbial composition of little penguin and short-tailed shearwater chicks throughout development, using Quantitative Real Time PCR (qPCR) and 16S rRNA sequencing.

Pragmatic Randomized, Controlled Trial of Patient Navigators and Enhanced Personal Health Records in CKD.

Background And Objectives: Patient navigators and enhanced personal health records improve the quality of health care delivered in other disease states. We aimed to develop a navigator program for patients with CKD and an electronic health record-based enhanced personal health record to disseminate CKD stage-specific goals of care and education. We also conducted a pragmatic randomized clinical trial to compare the effect of a navigator program for patients with CKD with enhanced personal health record and compare their combination compared with usual care among patients with CKD stage 3b/4.