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Galloylated flavonol rhamnosides from the leaves of Calliandra tergemina with antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA)

Chan EW, Gray AI, Igoli JO, Lee SM, Goh JK

Phytochemistry, 2014 Nov;107:148-54.
PMID: 25174555 DOI: 10.1016/j.phytochem.2014.07.028

Galloylated flavonol rhamnosides identified as kaempferol-3-O-(2″,3″,4″-tri-O-galloyl)-α-l-rhamnopyranoside, quercetin-3-O-(3″,4″-di-O-galloyl)-α-l-rhamnopyranoside, and quercetin-3-O-(2″,3″,4″-tri-O-galloyl)-α-l-rhamnopyranoside, together with five known galloylated and non-galloylated flavonol rhamnosides, were isolated from leaves of Calliandra tergemina (L.) Benth. Their structures were established using spectroscopic methods and their antibacterial activities against methicillin-resistant Staphylococcus aureus (MRSA) were evaluated by a microdilution method.
Snapper: high-sensitive detection of methylation motifs based on Oxford Nanopore reads

Konanov DN, Babenko VV, Belova AM, Madan AG, Boldyreva DI, Glushenko OE, et al.

Bioinformatics, 2023 Nov 20.
PMID: 37982752 DOI: 10.1093/bioinformatics/btad702

MOTIVATION: The Oxford Nanopore technology has a great potential for the analysis of methylated motifs in genomes, including whole genome methylome profiling. However, we found that there are no methylation motifs detection algorithms which would be sensitive enough and return deterministic results. Thus, the MEME suit does not extract all H. pylori methylation sites de novo even using the iterative manually controlled approach implemented in the most up-to-date methylation analysis tool Nanodisco.
RESULTS: We present Snapper, a new highly-sensitive approach to extract methylation motif sequences based on a greedy motif selection algorithm. Snapper does not require manual control during the enrichment process and has enrichment sensitivity higher than MEME coupled with Tombo or Nanodisco instruments that was demonstrated on H. pylori strain J99 studied earlier by the PacBio technology and on four external datasets representing different bacterial species. We used Snapper to characterize the total methylome of a new H.pylori strain A45. At least four methylation sites that have not been described for H. pylori earlier were revealed. We experimentally confirmed the presence of a new CCAG-specific methyltransferase and inferred a gene encoding a new CCAAK-specific methyltransferase.
AVAILABILITY: Snapper is implemented using Python and freely available as a pip package named 'snapper-ont'. Also, Snapper and the demo dataset are available in Zenodo (10.5281/zenodo.10117651).
SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
Fulltext Loss in lung volume and changes in the immune response demonstrate disease progression in African green monkeys infected by small-particle aerosol and intratracheal exposure to Nipah virus

Cong Y, Lentz MR, Lara A, Alexander I, Bartos C, Bohannon JK, et al.

PLoS Negl Trop Dis, 2017 04;11(4):e0005532.
PMID: 28388650 DOI: 10.1371/journal.pntd.0005532

Nipah virus (NiV) is a paramyxovirus (genus Henipavirus) that emerged in the late 1990s in Malaysia and has since been identified as the cause of sporadic outbreaks of severe febrile disease in Bangladesh and India. NiV infection is frequently associated with severe respiratory or neurological disease in infected humans with transmission to humans through inhalation, contact or consumption of NiV contaminated foods. In the work presented here, the development of disease was investigated in the African Green Monkey (AGM) model following intratracheal (IT) and, for the first time, small-particle aerosol administration of NiV. This study utilized computed tomography (CT) and magnetic resonance imaging (MRI) to temporally assess disease progression. The host immune response and changes in immune cell populations over the course of disease were also evaluated. This study found that IT and small-particle administration of NiV caused similar disease progression, but that IT inoculation induced significant congestion in the lungs while disease following small-particle aerosol inoculation was largely confined to the lower respiratory tract. Quantitative assessment of changes in lung volume found up to a 45% loss in IT inoculated animals. None of the subjects in this study developed overt neurological disease, a finding that was supported by MRI analysis. The development of neutralizing antibodies was not apparent over the 8-10 day course of disease, but changes in cytokine response in all animals and activated CD8+ T cell numbers suggest the onset of cell-mediated immunity. These studies demonstrate that IT and small-particle aerosol infection with NiV in the AGM model leads to a severe respiratory disease devoid of neurological indications. This work also suggests that extending the disease course or minimizing the impact of the respiratory component is critical to developing a model that has a neurological component and more accurately reflects the human condition.
Subcutaneous versus Intravenous Amivantamab, both in Combination with Lazertinib, in Refractory EGFR-mutated NSCLC: Primary Results from the Phase 3 PALOMA-3 Study

Leighl NB, Akamatsu H, Lim SM, Cheng Y, Minchom AR, Marmarelis ME, et al.

J Clin Oncol, 2024 Jun 10.
PMID: 38857463 DOI: 10.1200/JCO.24.01001

PURPOSE: Phase 3 studies of intravenous amivantamab demonstrated efficacy across EGFR-mutated advanced non-small cell lung cancer (NSCLC). A subcutaneous formulation could improve tolerability and reduce administration time while maintaining efficacy.
PATIENTS AND METHODS: Patients with EGFR-mutated advanced NSCLC who progressed following osimertinib and platinum-based chemotherapy were randomized 1:1 to receive subcutaneous or intravenous amivantamab, both combined with lazertinib. Co-primary pharmacokinetic noninferiority endpoints were trough concentrations (Ctrough; on cycle-2-day-1 or cycle-4-day-1) and cycle-2 area under the curve (AUCD1-D15). Key secondary endpoints were objective response rate (ORR) and progression-free survival (PFS). Overall survival (OS) was a predefined exploratory endpoint.
RESULTS: Overall, 418 patients underwent randomization (subcutaneous group, n=206; intravenous group, n=212). Geometric mean ratios of Ctrough for subcutaneous to intravenous amivantamab were 1.15 (90% CI, 1.04-1.26) at cycle-2-day-1 and 1.42 (90% CI, 1.27-1.61) at cycle-4-day-1; the cycle-2 AUCD1-D15 was 1.03 (90% CI, 0.98-1.09). ORR was 30% in the subcutaneous and 33% in the intravenous group; median PFS was 6.1 and 4.3 months, respectively. OS was significantly longer in the subcutaneous versus intravenous group (hazard ratio for death, 0.62; 95% CI, 0.42-0.92; nominal P=0.02). Fewer patients in the subcutaneous group experienced infusion-related reactions (13% versus 66%) and venous thromboembolism (9% versus 14%) versus the intravenous group. Median administration time for first infusion was reduced to 4.8 minutes (range, 0-18) for subcutaneous amivantamab from 5 hours (range, 0.2-9.9) for intravenous amivantamab. During cycle-1-day-1, 85% and 52% of patients in the subcutaneous and intravenous groups, respectively, considered treatment convenient; end-of-treatment rates were 85% and 35%, respectively.
CONCLUSION: Subcutaneous amivantamab-lazertinib demonstrated noninferiority to intravenous amivantamab-lazertinib, offering a consistent safety profile with reduced infusion-related reactions, increased convenience, and prolonged survival.