Ecto-5′-nucleotidase and intestinal ion secretion by enteropathogenic Escherichia coli

Enteropathogenic Escherichia coli (EPEC) triggers a large release of adenosine triphosphate (ATP) from host intestinal cells and the extracellular ATP is broken down to adenosine diphosphate (ADP), AMP, and adenosine. Adenosine is a potent secretagogue in the small and large intestine. We suspected that ecto-5′-nucleotidase (CD73, an intestinal enzyme) was a critical enzyme involved in the conversion of AMP to adenosine and in the pathogenesis of EPEC diarrhea. We developed a nonradioactive method for measuring ecto-5′-nucleotidase in cultured T84 cell monolayers based on the detection of phosphate release from 5′-AMP. EPEC infection triggered a release of ecto-5′-nucleotidase from the cell surface into the supernatant medium. EPEC-induced 5′-nucleotidase release was not correlated with host cell death but instead with activation of phosphatidylinositol-specific phospholipase C (PI-PLC). Ecto-5′-nucleotidase was susceptible to inhibition by zinc acetate and by α,β-methylene-adenosine diphosphate (α,β-methylene-ADP). In the Ussing chamber, these inhibitors could reverse the chloride secretory responses triggered by 5′-AMP. In addition, α,β-methylene-ADP and zinc blocked the ability of 5′-AMP to stimulate EPEC growth under nutrient-limited conditions in vitro. Ecto-5′-nucleotidase appears to be the major enzyme responsible for generation of adenosine from adenine nucleotides in the T84 cell line, and inhibitors of ecto-5′-nucleotidase, such as α,β-methylene-ADP and zinc, might be useful for treatment of the watery diarrhea produced by EPEC infection

SARS-CoV-2 infects the human kidney and drives fibrosis in kidney organoids

Kidney failure is frequently observed during and after COVID-19, but it remains elusive whether this is a direct effect of the virus. Here, we report that SARS-CoV-2 directly infects kidney cells and is associated with increased tubule-interstitial kidney fibrosis in patient autopsy samples. To study direct effects of the virus on the kidney independent of systemic effects of COVID-19, we infected human-induced pluripotent stem-cell-derived kidney organoids with SARS-CoV-2. Single-cell RNA sequencing indicated injury and dedifferentiation of infected cells with activation of profibrotic signaling pathways. Importantly, SARS-CoV-2 infection also led to increased collagen 1 protein expression in organoids. A SARS-CoV-2 protease inhibitor was able to ameliorate the infection of kidney cells by SARS-CoV-2. Our results suggest that SARS-CoV-2 can directly infect kidney cells and induce cell injury with subsequent fibrosis. These data could explain both acute kidney injury in COVID-19 patients and the development of chronic kidney disease in long COVID

Paleontology of leaf beetles

`The rate of evolution in any large group is not uniform; there are periods of relatise stability, and periods of comparatively rapid change.' Cockerell and LeVeque, 1931 To Yenli Ych, my beloved wife, a most wonderful person! The fossil record of the Chrysomelidae can be tentatively traced back to the late Paleozoic to early Mesozoic Triassic. Mesozoic records at least 9 subfamilies, 19 genera, and 35 species, are represented by the Sagrinae, the exclusively Mesozoic Proto scelinae, Clytrinae, Cryptocephalinae, Eumolpinae, Chrysomelinae. Galerucinac, Alticinae, and Cassidinae. Cenozoic records at least 12 subfamilies- 63 % of the extant- 12! genera, and 325 species, include the same extant subfamilies as well as the Donaciinae, Zeugophorinae, Criocerinae, and Hispinae and can be frequently identified to genus, especially if preserved in amber. Quaternary records are often identified to extant species. tn total, at least t3! genera about 4 % of total extant, and 357 species < 1 % have been reported. At least, 24 genera <1 % of the extant seem to be extinct. Although reliable biological information associated with the fossil chrysomelids is very scarce, it seems that most of the modern host-plant associations were established, at least, in the late Mesozoic to early Cenozoic. As a whole, stasis seems to be the general rule of the chrysomelid fossil record. Together with other faunal elements, chrysomelids, especially donaciines, have been used as biogeographic and paleoclimatological indicators in the Holocene. I

Bicultural development within an early childhood teacher education programme

This paper reports findings from a doctoral study which focused on processes implemented within an early childhood teacher education programme at the University of Waikato in Hamilton, New Zealand, that aimed to deliver on a stated commitment to Te Tiriti o Waitangi/the Treaty of Waitangi. This 1840 treaty guaranteed protection to Māori, the indigenous people of Aotearoa/New Zealand. As a result of the impact of colonisation by Britain, Māori have become marginalised within their own country, and their language is threatened. Recognition of the treaty necessitates a restorative process that may be termed ‘bicultural development’. This paper describes key features of the bicultural development process implemented within this teacher education programme