Large airway complications in COVID-19 pneumonia.

COVID-19 pneumonia can cause respiratory failure which requires specialist management. However the inflammatory nature of the condition and the interventions necessary to manage these patients such as endotracheal intubation and tracheostomy can lead to large airway pathology which may go unrecognised. We describe five of the 44 (11%) consecutive patients referred to our specialist ARDS team between April and June 2020 with confirmed COVID-19 pneumonia who developed diverse large airway pathology which comprised of: supraglottic oedema, tracheal tear, tracheal granulation tissue formation, bronchomalacia, and tracheal diverticulum.

Pulmonary function, computerized tomography features and six-minute walk test at three months in severe COVID-19 patients treated with intravenous pulsed methylprednisolone: a preliminary report.

COVID-19 acute respiratory distress syndrome (ARDS) has a high mortality and few therapeutic options. We present a preliminary report on our experience using high-dose pulsed methylprednisolone in COVID-19 ARDS and three-month outcomes. We performed a retrospective analysis of all patients treated with high-dose methylprednisolone for COVID-19 ARDS and three-month lung function, 6-minutes walking test (6MWT), and computerized tomography (CT) findings.

A specialised cardiorespiratory team approach in the intensive care management of COVID-19 patients: benefit on mortality, diagnosis and management.

Background: During the coronavirus pandemic, our intensive care units were faced with large numbers of patients with an unfamiliar disease. To support our colleagues and to assist with diagnosis and treatment, we developed a specialist team.

Methods: The acute respiratory disease support team reviewed 44 consecutive patients referred from the intensive care and coordinated therapies for pulmonary hypertension, pulmonary thrombosis, evolving lung fibrosis and large airway intervention.

Rapid access to Asp/Glu sidechain hydrazides as thioester precursors for peptide cyclization and glycosylation.

Head-to-sidechain macrocylic peptides, and neoglycopeptides, were readily prepared by site-specific amidation of aspartic and glutamic acid sidechain hydrazides. Hydrazides, serving as latent thioesters, were introduced through regioselective opening of the corresponding Nα-Fmoc protected anhydride precursors.

A 2-step synthesis of Combretastatin A-4 and derivatives as potent tubulin assembly inhibitors.

A series of combretastatin derivatives were designed and synthesised by a two-step stereoselective synthesis by use of Wittig olefination followed by Suzuki cross-coupling. Interestingly, all new compounds (2a-2i) showed potent cell-based antiproliferative activities in nanomolar concentrations. Among the compounds, 2a, 2b and 2e were the most active across three cancer cell lines.

Genetic Variants Associated with Cancer Pain and Response to Opioid Analgesics: Implications for Precision Pain Management.

Objective: To review the current knowledge on the association of genetic variants with cancer pain.

Data Sources: Data-based publications and review articles retrieved from PubMed, CINAHL, and Web of Science, as well as an additional search in Google Scholar.

Conclusion: Genetic variability can influence differential pain perception and response to opioids in cancer patients, which will have implications in the optimal personalized treatment of cancer pain.

Thermal challenge alters the transcriptional profile of the breast muscle in turkey poults.

Extremes in temperature represent environmental stressors that impact the well-being and economic value of poultry. As homeotherms, young poultry with immature thermoregulatory systems are especially susceptible to thermal extremes. Genetic variation and differences in gene expression resulting from selection for production traits, likely contribute to thermal stress response.

Response of turkey muscle satellite cells to thermal challenge. I. transcriptome effects in proliferating cells.

Background: Climate change poses a multi-dimensional threat to food and agricultural systems as a result of increased risk to animal growth, development, health, and food product quality. This study was designed to characterize transcriptional changes induced in turkey muscle satellite cells cultured under cold or hot thermal challenge to better define molecular mechanisms by which thermal stress alters breast muscle ultrastructure.

Results: Satellite cells isolated from the pectoralis major muscle of 7-weeks-old male turkeys from two breeding lines (16 weeks body weight-selected and it's randombred control) were proliferated in culture at 33 °C, 38 °C or 43 °C for 72 h.

Environmental metabarcoding reveals heterogeneous drivers of microbial eukaryote diversity in contrasting estuarine ecosystems.

Assessing how natural environmental drivers affect biodiversity underpins our understanding of the relationships between complex biotic and ecological factors in natural ecosystems. Of all ecosystems, anthropogenically important estuaries represent a 'melting pot' of environmental stressors, typified by extreme salinity variations and associated biological complexity. Although existing models attempt to predict macroorganismal diversity over estuarine salinity gradients, attempts to model microbial biodiversity are limited for eukaryotes.

Species-specific effect of macrobenthic assemblages on meiobenthos and nematode community structure in shallow sandy sediments.

Three functionally different macrofaunal species (the filter- and/or surface deposit-feeding polychaete , and the suspension-feeding bivalves and ) were introduced as single- and two-species treatments into microcosms containing sandy sediment with a natural meiofaunal community. is a burrowing species building a system of galleries, lives actively near the sediment surface acting as a biodiffuser and buries deeply and leads a sessile lifestyle. It is shown that extended the vertical distribution of meiofauna into deeper sediment layers compared to the control and non- treatments.

DNMT3B7, a truncated DNMT3B isoform expressed in human tumors, disrupts embryonic development and accelerates lymphomagenesis.

Epigenetic changes are among the most common alterations observed in cancer cells, yet the mechanism by which cancer cells acquire and maintain abnormal DNA methylation patterns is not understood. Cancer cells have an altered distribution of DNA methylation and express aberrant DNA methyltransferase 3B transcripts, which encode truncated proteins, some of which lack the COOH-terminal catalytic domain. To test if a truncated DNMT3B isoform disrupts DNA methylation in vivo, we constructed two lines of transgenic mice expressing DNMT3B7, a truncated DNMT3B isoform commonly found in cancer cells.

Cell-specific trafficking suggests a new role for renal ATP7B in the intracellular copper storage.

Human Cu-ATPases ATP7A and ATP7B maintain copper homeostasis through regulated trafficking between intracellular compartments. Inactivation of these transporters causes Menkes disease and Wilson disease, respectively. In Menkes disease, copper accumulates in kidneys and causes tubular damage, indicating that the renal ATP7B does not compensate for the loss of ATP7A function.

Steady-state increase of cAMP-response element binding protein, Rac, and PAK signaling in presenilin-deficient neurons.

Mutations in the genes encoding presenilins (PS1 and PS2) account for the majority of cases of early-onset Alzheimer's disease. PS1 and PS2 form the catalytic center of gamma-secretase, an enzyme responsible for intramembraneous proteolysis of several type I transmembrane proteins. Many gamma-secretase substrates are coupled to intracellular signaling events such as cAMP-response element binding protein and Rac1/p21-activated kinase pathways, which are associated with synaptic function.

Function and regulation of human copper-transporting ATPases.

Copper-transporting ATPases (Cu-ATPases) ATP7A and ATP7B are evolutionarily conserved polytopic membrane proteins with essential roles in human physiology. The Cu-ATPases are expressed in most tissues, and their transport activity is crucial for central nervous system development, liver function, connective tissue formation, and many other physiological processes. The loss of ATP7A or ATP7B function is associated with severe metabolic disorders, Menkes disease, and Wilson disease.

Spatial segregation of gamma-secretase and substrates in distinct membrane domains.

Gamma-secretase facilitates the regulated intramembrane proteolysis of select type I membrane proteins that play diverse physiological roles in multiple cell types and tissue. In this study, we used biochemical approaches to examine the distribution of amyloid precursor protein (APP) and several additional gamma-secretase substrates in membrane microdomains. We report that APP C-terminal fragments (CTFs) and gamma-secretase reside in Lubrol WX detergent-insoluble membranes (DIM) of cultured cells and adult mouse brain.

Presenilin attenuates receptor-mediated signaling and synaptic function.

Presenilin (PS) plays an essential role in intramembranous gamma-secretase processing of amyloid precursor protein (APP) and several membrane-bound proteins. Here we report that selective accumulation of a membrane-tethered deleted in colorectal cancer (DCC) derivative (DCC-alpha) correlates with extensive neurite outgrowth in transfected neuroblastoma cells and axodendritic connectivity associated with increased spine density in cortical neurons derived from PS1(-/-) embryos, as well as wild-type neurons treated with gamma-secretase inhibitors. cAMP-dependent signaling was also increased in both the neuroblastoma and cortical neuron systems.

The copper-transporting ATPases, menkes and wilson disease proteins, have distinct roles in adult and developing cerebellum.

Copper is essential for brain metabolism, serving as a cofactor to superoxide dismutase, dopamine-beta-hydroxylase, amyloid precursor protein, ceruloplasmin, and other proteins required for normal brain function. The copper-transporting ATPases ATP7A and ATP7B play a central role in distribution of copper in the central nervous system; genetic mutations in ATP7A and ATP7B lead to severe neurodegenerative disorders, Menkes disease and Wilson disease, respectively. Although both ATP7A and ATP7B are required, their specific roles and regulation in the brain remain poorly understood.

Copper-induced trafficking of the cU-ATPases: a key mechanism for copper homeostasis.

The Menkes protein (MNK) and Wilson protein (WND) are transmembrane, CPX-type Cu-ATPases with six metal binding sites (MBSs) in the N-terminal region containing the motif GMXCXXC. In cells cultured in low copper concentration MNK and WND localize to the transGolgi network but in high copper relocalize either to the plasma membrane (MNK) or a vesicular compartment (WND). In this paper we investigate the role of the MBSs in Cu-transport and trafficking.