Maternal Administration of Solithromycin, a New, Potent, Broad-Spectrum Fluoroketolide Antibiotic, Achieves Fetal and Intra-Amniotic Antimicrobial Protection in a Pregnant Sheep Model

Solithromycin (CEM-101) is a new antibiotic that is highly potent against Ureaplasma and Mycoplasma spp. and active against many other antibiotic-resistant organisms. We have explored the maternal-amniotic-fetal pharmacokinetics of CEM-101 in a pregnant sheep model to assess its potential for treating intrauterine and antenatal infection. Chronically catheterized pregnant ewes (n = 6 or 7) received either a single maternal intravenous (i.v.) infusion of CEM-101 (10 mg/kg of body weight), a single intra-amniotic (i.a.) injection (1.4 mg/kg of estimated fetal weight), or a combined i.v. and i.a. dose. Maternal plasma (MP), fetal plasma (FP), and amniotic fluid (AF) samples were taken via catheter at intervals of 0 to 72 h postadministration, and concentrations of solithromycin and its bioactive polar metabolites (N-acetyl [NAc]–CEM-101 and CEM-214) were determined. Following maternal i.v. infusion, peak CEM-101 concentrations in MP, FP, and AF were 1,073, 353, and 214 ng/ml, respectively, representing a maternal-to-fetal plasma transfer efficiency of 34%. A single maternal dose resulted in effective concentrations (>30 ng/ml) in MP, FP, and AF sustained for >12 h. NAc–CEM-101 and CEM-214 exhibited delayed accumulation and clearance in FP and AF, resulting in an additive antimicrobial effect (>48 h). Intra-amniotic solithromycin injection resulted in elevated (∼50 μg/ml) and sustained CEM-101 concentrations in AF and significant levels in FP, although the efficiency of amniotic-to-fetal transfer was low (∼1.5%). Combined i.v. and i.a. administration resulted in primarily additive concentrations of CEM-101 in all three compartments. Our findings suggest that CEM-101 may provide, for the first time, an effective antimicrobial approach for the prevention and treatment of intrauterine infection and early prevention of preterm birth

fwt_historic

Dataset of past FWT winners 1996-2018<br

Transcriptome Dynamics Over a Lunar Cycle in Acropora humilis

The cycle of the moon serves as a cue for the reproduction of many species of corals, with many species spawning in the evening a few days following a full moon. Yet, little is known about the molecular mechanisms that allow corals to perceive moonlight and use this information for reproductive timing. To improve our understanding, short-read sequencing was used to assemble, de novo, the transcriptome of the coral Acropora humilis and identify differential patterns of gene expression in the month preceding spawning. Analysis revealed a number of biological processes that change over the lunar month including energy metabolism, skeletal deposition and translation. Furthermore, a number of circadian clock genes shift their expression over the lunar month suggesting a potential mechanism that corals may use detect moonlight and trigger a biochemical cascade that culminates in gamete release following the full moon

fwt_standings.csv

Dataset of all FWT winners from the 23 tours between 1996 and 2018 and added the age of the riders from either the FWT website or a brief web-search (some missing).<br

fwt_roster_2018

Dataset of the FWT 2018 roster.<br

Transcriptome dynamics over a lunar month in a broadcast spawning acroporid coral

On one night per year, at a specific point in the lunar cycle, one of the most extraordinary reproductive events on the planet unfolds as hundreds of millions of broadcast spawning corals release their trillions of gametes into the waters of the tropical seas. Each species spawns on a specific night within the lunar cycle, typically from full moon to third quarter moon, and in a specific time window after sunset. This accuracy is essential to achieve efficient fertilization in the vastness of the oceans. In this report, we use transcriptome sequencing at noon and midnight across an entire lunar cycle to explore how acroporid corals interpret lunar signals. The data were interrogated by both time-of-day-dependent and time-of-day-independent methods to identify different types of lunar cycles. Time-of-day methods found that genes associated with biological clocks and circadian processes change their diurnal cycles over the course of a synodic lunar cycle. Some genes have large differences between day and night at some lunar phases, but little or no diurnal differences at other phases. Many clock genes display an oscillation pattern indicative of phase shifts linked to the lunar cycle. Time-independent methods found that signal transduction, protein secretion and modification, cell cycle and ion transport change over the lunar timescale and peak at various phases of the moon. Together these data provide unique insights into how the moon impinges on coral transcription cycles and how lunar light may regulate circalunar timing systems and coral biology

GLM new GO annotations

Blast2GO updates of annotations for DE genes detected by GL

salmon_count_table

Read count table from Salmon light-weight alignmen

amil.fasta

The A. millepora transcriptome used for alignments in this study. This is based on the transcriptome of Moya et al. (PMID 22490231) modified by the Matz lab

NormalizedCount-lab-labels

Normalized read counts generated by DESeq2 LRT analysi