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AbstractRecent excavations at Millukmungee 1, a limestone rock shelter along the upper bank of the Buchan River in GunaiKurnai Country (southeastern Australia), uncovered archaeological evidence of Mid- to Late Holocene occupation spanning c. 5000 years. Here we report on the stone artefacts and faunal remains, especially in light of a paucity of published details on artefact types and technologies for this part of southeast Australia. Results indicate that this part of the site was occupied only rarely from 5590–5050 cal BP(the uncertainty range for the oldest artefact from the excavation) to 2340–2030 cal BP. During this period, most of the artefacts were made from silcrete, quartz, chert, and quartzite. Small backed artefacts are present during this phase, all dating between 4570–1940 cal BP. A single, much larger backed artefact (elouera) dates to later, ≤290 cal BP. After 1960 cal BP, activities focussed on the production of flakes from locally available quartz and, to a lesser extent, hornfels; large pebbles obtained from the nearby Buchan River channel were flaked during this period. Occupation ceased with the onset of settler colonialism in the mid-1800s CE.

AbstractSeafaring ceramicists connected widely spaced communities along the expanse of PNG’s south coast for more than 1,500 years following the arrival of people using pots with Lapita decoration c.2,900 cal BP. Archaeological investigations at locations from the Gulf of Papua in the west to Mailu Island in the east suggest a major change occurred to seafaring and social relations after 1,200 cal BP. The following five centuries often referred to as the ‘Ceramic Hiccup’ were characterised by a contraction in the scale of formerly long-distance voyaging. Here we present results of recent archaeological excavations at the ancestral village site of Agila in Hood Bay east of Port Moresby. The decorations on older pot sherds at Agila are akin to those on ancestral Motu pottery known from Motupore Island to the west. The decoration changes on more recent sherds which have more in common with ancestral Mailu pottery from Mailu Island to the east. Details of changing seafaring relations – from west to east – at Agila were published in 2018 after our first field season. However, results from the first field season left questions about site antiquity unresolved. We returned to Agila in 2022 and continued excavations to address those questions. Our excavations revealed that initial settlement at Agila coincided with a reanimation of coastal seafaring after 770 cal BP. Results also show that the major pottery manufacturing and seafaring community of Motupore maintained relations with communities to both the east and west. An analysis of the ceramic assemblage allows us to historicise the emergence of social strategies which entrenched Hood Bay at a nexus between Motu and Mailu specialised trading and seafaring communities.

Proper regulation of protein homeostasis (proteostasis) is essential for all organisms to survive. A diverse range of post-translational modifications (PTMs) allow precise control of protein abundance, function and cellular localisation. In eukaryotic cells, ubiquitination is a widespread, essential PTM that regulates most, if not all cellular processes. Ubiquitin is added to target proteins via a well-defined enzymatic cascade involving a range of conjugating enzymes and ligases, while its removal is catalysed by a class of enzymes known as deubiquitinases (DUBs). Many human diseases have now been linked to DUB dysfunction, demonstrating the importance of these enzymes in maintaining cellular function. These findings have led to a recent explosion in studying the structure, molecular mechanisms and physiology of DUBs in mammalian systems. Plant DUBs have however remained relatively understudied, with many DUBs identified but their substrates, binding partners and the cellular pathways they regulate only now beginning to emerge. This review focuses on the most recent findings in plant DUB biology, particularly on newly identified DUB substrates and how these offer clues to the wide-ranging roles that DUBs play in the cell. Furthermore, the future outlook on how new technologies in mammalian systems can accelerate the plant DUB field forward is discussed.

ABSTRACTInfection with intravascular platyhelminths of the genus Schistosomacan result in the debilitating disease schistosomiasis. Schistosomes (blood flukes) can survive in the host for many years. We hypothesize that proteins on their host-interactive surface modify the worm’s external environment to help insure worm survival. Previously, we have shown that a surface ectoenzyme of Schistosoma mansoni, SmNPP5 – a nucleotide pyrophosphatase/phosphodiesterase – can cleave ADP and block platelet aggregation in vitro. In this work, we show that both adult schistosomes and recombinant SmNPP5 can cleave the exogenous purinergic signaling molecule nicotinamide adenine dinucleotide (NAD). In doing so, worms and rSmNPP5 can prevent NAD-induced apoptosis of T cells in vitro. Since regulatory T cells (Tregs) are especially prone to such NAD-induced cell death (NICD), we hypothesize that schistosome cleavage of NAD promotes Treg survival which creates a more immunologically hospitable environment for the worms in vivo. In addition to SmNPP5, schistosomes express another host-interactive NAD-degrading enzyme, SmNACE. We successfully suppressed the expression of SmNPP5 and SmNACE (singly or together) using RNAi. Only SmNPP5-suppressed worms, and not SmNACE-suppressed worms, were significantly impaired in their ability to cleave exogenous NAD compared to controls. Therefore, we contend that ectoenzyme SmNPP5 on the surface of the worm is primarily responsible for extracellular NAD cleavage and that this helps modulate the host immune environment by preventing Treg cell death.

AbstractThe ‘direct’ dating of rock art has proliferated since the development of accelerator mass spectrometry radiocarbon, uranium-series and optically stimulated luminescence dating, yet still, most rock art is not directly datable due to the mineral nature of the constituent pigments. Here we present another method: the recovery and dating by stratigraphic association of small buried fragments of ochre and dried paint drops deposited onto soft sediment surfaces as by-products of paint production and use. These finds also give added contextual occupational information for archaeology of painting events. The case is made through the example of Borologa 1, a richly decorated Wanjina rockshelter in the Kimberley region of northwestern Australia that contains buried hearths, grindstones, earth pigments and small fallen spalls of rock containing traces of pigment and paint drops. Results from excavation indicate the beginning of Wanjina motifs and associated painting conventions on Art Panel B1 sometime between 2,080–1,160 cal BP and their proliferation in the past millennium.

Schistosomiasis is a debilitating parasitic disease caused by intravascular flatworms called schistosomes (blood flukes) that affects >200 million people worldwide. Proteomic analysis has revealed the surprising presence of classical glycolytic enzymes – typically cytosolic proteins – located on the extracellular surface of the parasite tegument (skin). Immunolocalization experiments show that phosphoglycerate mutase (PGM) is widely expressed in parasite tissues and is highly expressed in the tegument. We demonstrate that live Schistosoma mansoniparasites express enzymatically active PGM on their tegumental surface. Suppression of PGM using RNA interference (RNAi) diminishes S. mansoniPGM (SmPGM) gene expression, protein levels, and surface enzyme activity. Sequence comparisons place SmPGM in the cofactor (2,3-bisphosphoglycerate)-dependent PGM (dPGM) family. We have produced recombinant SmPGM (rSmPGM) in an enzymatically active form in Escherichia coli. The Michaelis-Menten constant (Km) of rSmPGM for its glycolytic substrate (3-phosphoglycerate) is 0.85 mM ± 0.02. rSmPGM activity is inhibited by the dPGM-specific inhibitor vanadate. Here, we show that rSmPGM not only binds to plasminogen but also promotes its conversion to an active form (plasmin) in vitro. This supports the hypothesis that host-interactive tegumental proteins (such as SmPGM), by enhancing plasmin formation, may help degrade blood clots around the worms in the vascular microenvironment and thus promote parasite survival in vivo.

The Unit 6 intake system at Niagara Mohawk Power Corporation's Oswego Steam Station Unit 6 is designed to mitigate periodic losses of Lake Ontario fish by bypassing and returning to the lake those fish that enter the offshore intake. Fish are diverted along four traveling water screens installed in a chevron arrangement angled with respect to the flow. Jet pumps provide bypass flow necessary for fish return to the lake. Three years of information on the operational and biological effectiveness of the angledscreen fish diversion system are presented and discussed. System components are discussed in terms of maintenance requirements and operation relative to an adjacent conventional intake system Unit 5. Hydraulic measurements are also presented. Biological effectiveness of this system is compared with that of a oncethrough system with conventional vertical traveling screens. Evaluation of fish survival up to 96 hrs after diversion indicates seasonal and speciesspecific survival.

Herpes simplex virus-1 (HSV-1) is the most common cause of lethal sporadic encephalitis. Despite improved therapy with intraveneous acyclovir, HSV-1 encephalitis is associated with persistent severe neurological deficits. We report three cases of adult patients with HSV-1 encephalitis (HSE), discuss the current accepted guidelines for treatment as published by the Infectious Disease Society of America (IDSA) and review the literature pertaining to HSE. Our case presentations are consistent with the literature review noting a broad spectrum of clinical outcomes with HSE. We include the first published case of successful early transition to oral antiviral therapy. In the other two cases, repeat cerebrospinal fluid (CSF) analysis showed persistent lymphocytic pleocytosis necessitating prolonged viral suppression. Long-term neurological sequelae were noted in these two patients. The IDSA recommendation of 2–3 weeks of intraveneous acyclovir at 10 mg/kg every 8 h, depending on the clinical course, is sufficient for most cases of HSE. We recommend individualization of duration of treatment based on follow-up CSF analysis with quantification of HSV-1.

ABSTRACTThe intravascular trematode Schistosoma mansoniis a causative agent of schistosomiasis, a disease that constitutes a major health problem globally. In this study we cloned and characterized the schistosome tegumental phosphodiesterase SmNPP-5 and evaluated its role in parasite virulence. SmNPP-5 is a 52.5-kDa protein whose gene is rapidly turned on in the intravascular parasitic life stages, following invasion of the definitive host. Highest expression is found in mated adult males. As revealed by immunofluorescence analysis, SmNPP-5 protein is found prominently in the dorsal surface of the tegument of males. Localization by immuno-electron microscopy illustrates a unique pattern of immunogold-labeled SmNPP-5 within the tegument; some immunogold particles are scattered throughout the tissue, but many are clustered in tight arrays. To determine the importance of the protein for the parasites, RNA interference (RNAi) was employed to knock down expression of the SmNPP-5-encoding gene in schistosomula and adult worms. Both quantitative real-time PCR (qRT-PCR) and Western blotting confirmed successful and robust gene suppression. In addition, the suppression and the ectolocalization of this enzyme in live parasites were evident because of a significantly impaired ability of the suppressed parasites to hydrolyze exogenously added phosphodiesterase substrate p-nitrophenyl 5′-dTMP (p-Nph-5′-TMP). The effects of suppressing expression of the SmNPP-5 gene in vivowere tested by injecting parasites into mice. It was found that, unlike controls, parasites whose SmNPP-5 gene was demonstrably suppressed at the time of host infection were greatly impaired in their ability to establish infection. These results demonstrate that SmNPP-5 is a virulence factor for schistosomes.

Objectives: To review the records of 29 dogs diagnosed with primary hyperparathyroidism and see if any factors correlate with renal failure.

Hyperadrenocorticism occurs much less frequently in cats than in dogs and, at present, is more difficult to manage successfully. This report documents the use of the steroid synthesis inhibitor trilostane for the treatment of hyperadrenocorticism in a domestic shorthaired cat with pituitary‐dependent disease. Although trilostane was able to alleviate the severity of the clinical signs and was well tolerated, the cat subsequently died of renal failure secondary to a fungal infection of the urinary tract.

Lysosomal storage diseases are rare, inherited disorders caused by the deficiency of 1 or more enzymes within the lysosomes of cells or by the deficiency of an activating protein or cofactor necessary for enzyme activity. The enzyme deficiency leads to a catabolic blockade and subsequent accumulation of storage material, and this in turn leads, albeit indirectly, to a wide array of clinical signs. Many features of storage diseases make them difficult to recognize and diagnose. In this review, we summarize the clinical features of these diseases and outline the steps required to confirm a diagnosis.