Effects of high and low barometric pressures on susceptibility and resistance to infection Quarterly status report, 1 Apr. - 30 Jun. 1969

Effects of atmospheric pressure on susceptibility and resistance to infectio

Effects of high and low barometric pressures on susceptibility and resistance to infection Quarterly status report, 1 Oct. - 31 Dec. 1968

Effects of high and low barometric pressures on susceptibility and resistance to infection in mic

Effects of high and low barometric pressures on susceptibility and resistance to infection Quarterly status report, 1 Jul. - 30 Sep. 1969

Atmospheric pressure effects on mice resistance to bacterial or virus infection

An Analysis of Putative Roles for the CCR4-NOT Deadenylase-Complex Subunit Regena (NOT2) in microRNA-Mediated Gene Silencing in \u3cem\u3eDrosophila Melanogaster\u3c/em\u3e

microRNAs (miRNAs) are one class of small non-coding ribonucleic acid (RNA) molecules essential to development and homeostasis in plants and animals. miRNAs silence gene expression through complementary base pairing with target gene messenger RNAs and association with the miRNA-induced silencing complex (miRISC). The identification and characterization of cellular factors required for miRNA-mediated gene silencing is incomplete. A forward genetic screen was carried out in Drosophila melanogaster to generate flies defective for gene silencing. Silencing was assayed by expression of a Green Fluorescent Protein (GFP) reporter fused to the Brd gene 3’ UTR, which is regulated by miRNAs. Genetic analysis revealed that the CCR4-NOT deadenylase-complex subunit Regena (NOT2) is required for miRNA-mediated silencing of the reporter. In addition, perturbation of Regena function altered Drosophila eye development and resulting adult eye morphology. miRNAs are thought to silence target gene expression through a combination of translational repression and target mRNA degradation, though the detailed mechanism of this process is a matter of controversy. Novel genetic reagents to explore miRNA function in vivo have been generated and characterized. Ongoing efforts aim to explore whether Regena is required to silence other miRNA targets in vivo, and whether Regena is required for miRNA-mediated gene silencing at different stages of the Drosophila life cycle. Elucidation of the lesion in the Regena (NOT2) gene and the molecular nature of GFP reporter silencing will contribute to an understanding of the mechanism of miRNA-mediated gene silencing in vivo

Effects of high and low barometric pressures on susceptibility and resistance to infection Quarterly status report, 1 Apr. - 30 Jun. 1970

Effects of high and low barometric pressures on susceptibility and resistance to infectio

When to suspect and how to approach a diagnosis of amyloidosis

Diagnoses of amyloidosis, particularly transthyretin amyloid cardiomyopathy (ATTR-CM), are steadily increasing throughout the world but the condition remains underdiagnosed. Patients with amyloidosis may present to a range of medical and surgical specialties, often with multi-system disease, and a high index of clinical suspicion is required for diagnosis. Bone scintigraphy and cardiovascular magnetic resonance imaging (CMR) offer highly sensitive and specific imaging modalities for cardiac amyloidosis. Histological confirmation of amyloid deposition and amyloid type remains the cornerstone of diagnosis for most amyloid types, with ATTR-CM the exception, which may be diagnosed by validated non-biopsy diagnostic criteria in the majority. Histological diagnosis of amyloid has been enhanced by laser capture microdissection and tandem mass spectrometry. Early diagnosis and treatment prior to the development of end organ damage remains key to improving morbidity and mortality for patients with amyloidosis

RNA Targeting and Gene Editing Strategies for Transthyretin Amyloidosis

Transthyretin (TTR) is a tetrameric protein synthesized primarily by the liver. TTR can misfold into pathogenic ATTR amyloid fibrils that deposit in the nerves and heart, causing a progressive and debilitating polyneuropathy (PN) and life-threatening cardiomyopathy (CM). Therapeutic strategies, which are aimed at reducing ongoing ATTR amyloid fibrillogenesis, include stabilization of the circulating TTR tetramer or reduction of TTR synthesis. Small interfering RNA (siRNA) or antisense oligonucleotide (ASO) drugs are highly effective at disrupting the complementary mRNA and inhibiting TTR synthesis. Since their development, patisiran (siRNA), vutrisiran (siRNA) and inotersen (ASO) have all been licensed for treatment of ATTR-PN, and early data suggest these drugs may have efficacy in treating ATTR-CM. An ongoing phase 3 clinical trial will evaluate the efficacy of eplontersen (ASO) in the treatment of both ATTR-PN and ATTR-CM, and a recent phase 1 trial demonstrated the safety of novel in vivo CRISPR-Cas9 gene-editing therapy in patients with ATTR amyloidosis. Recent results from trials of gene silencer and gene-editing therapies suggest these novel therapeutic agents have the potential to substantially alter the landscape of treatment for ATTR amyloidosis. Their success has already changed the perception of ATTR amyloidosis from a universally progressive and fatal disease to one that is treatable through availability of highly specific and effective disease-modifying therapies. However, important questions remain including long-term safety of these drugs, potential for off-target gene editing, and how best to monitor the cardiac response to treatment.Kindly check and confirm the processed running title.This is correct

Transthyretin cardiac amyloidosis

Transthyretin cardiac amyloidosis (ATTR-CA) is an increasingly recognized cause of heart failure (HF) and mortality worldwide. Advances in non-invasive diagnosis, coupled with the development of effective treatments, have shifted ATTR-CA from a rare and untreatable disease to a relatively prevalent condition that clinicians should consider on a daily basis. Amyloid fibril formation results from age-related failure of homoeostatic mechanisms in wild-type ATTR (ATTRwt) amyloidosis (non-hereditary form) or destabilizing mutations in variant ATTR (ATTRv) amyloidosis (hereditary form). Longitudinal large-scale studies in the United States suggest an incidence of cardiac amyloidosis in the contemporary era of 17 per 100 000, which has increased from a previous estimate of 0.5 per 100 000, which was almost certainly due to misdiagnosis and underestimated. The presence and degree of cardiac involvement is the leading cause of mortality both in ATTRwt and ATTRv amyloidosis, and can be identified in up to 15% of patients hospitalized for HF with preserved ejection fraction. Associated features, such as carpal tunnel syndrome, can preceed by several years the development of symptomatic HF and may serve as early disease markers. Echocardiography and cardiac magnetic resonance raise suspicion of disease and might offer markers of treatment response at a myocardial level, such as extracellular volume quantification. Radionuclide scintigraphy with ‘bone’ tracers coupled with biochemical tests may differentiate ATTR from light chain amyloidosis. Therapies able to slow or halt ATTR-CA progression and increase survival are now available. In this evolving scenario, early disease recognition is paramount to derive the greatest benefit from treatment