Pix1 and Pix2 are novel WD40 microtubule-associated proteins that colocalize with mitochondria in Xenopus germ plasm and centrosomes in human cells

In many animals, the germ line develops from a distinct mitochondria-rich region of embryonic cytoplasm called the germ plasm. However, the protein composition of germ plasm and its formation remain poorly understood, except in Drosophila. Here, we show that Xpat, a recently identified protein component of Xenopus germ plasm, interacts via its C-terminal domain with a novel protein, xPix1. Xpat and xPix1 are co-expressed in ovaries, eggs and early embryos and colocalize to the mitochondrial cloud and germ plasm in stage I and stage VI oocytes, respectively. Although Xpat appears unique to Xenopus, Pix proteins, which contain an N-terminal WD40 domain and C-terminal coiled-coil, are widely conserved. In humans, two proteins, Pix1 and Pix2, are expressed at varying levels in different cancer cell lines. Importantly, as well as localizing to mitochondria, human Pix proteins localize to centrosomes and associate with microtubules in vitro and in vivo. Although, Pix proteins are stably expressed through the cell cycle, Pix2 concentrates on microtubule structures in mitosis and microinjection of Fix antibodies interferes with cell division. Based on these data, we propose that Pix1 and Pix2 are microtubule-associated adaptor proteins that likely contribute to a range of developmental and cell division processes. (c) 2007 Elsevier Inc. All rights reserved

Holocene sea-level change in the Severn Estuary, southwest England: A diatom-based sea-level transfer function for macrotidal settings

The recent growth in the use of microfossil-based transfer functions in late-Quaternary sea-level reconstructions reflects their potential to accurately quantify palaeo sea-level changes. This study details the development of a diatom-based sea-level transfer function for the Severn Estuary, southwest England, a macrotidal setting that experiences the second highest tidal range in the world. This setting presents difficulties in representing the full tidal range from mean sea level (MSL) to highest astronomical tide (HAT). However, two separate transects were merged successfully and a statistically significant relationship between contemporary diatom assemblages and altitude (m O.D.) was established. A diatom-based transfer function for palaeoaltitude was developed using weighted averaging (WA), tolerance downweighted weighted averaging (WA-Tol) and weighted averaging partial least squares (WA-PLS). WA-Tol produced the lowest prediction errors for altitude and the transfer function was applied to a fossil diatom data set from Gordano Valley, a site adjacent to the Severn Estuary. © 2007 SAGE Publications

Devensian Late-glacial environmental change in the Gordano Valley, North Somerset, England: A rare archive for southwest Britain

The Late-glacial and Holocene environmental history of the Gordano Valley, North Somerset, UK has been reconstructed using pollen, sediment particle size and mineralogical analyses and radiocarbon dating. A Devensian sediment ridge across the valley confined the waters of a small lake, within which the initial sedimentation was minerogenic. Radiocarbon dating of overlying organic-rich deposits suggests that this began late in the Dimlington Stadial c. 18,000-15,000 Cal. BP. Petrographic analyses indicate the minerogenic sediments were partly wind-blown in origin. Climatic amelioration during the Windermere Interstadial c. 15,000 Cal. BP encouraged a shift from minerogenic to biogenic sedimentation. A brief return to minerogenic sedimentation between c. 10,400 and c. 9,520 Cal. BP was followed by uninterrupted fen peat accumulation throughout the Holocene. The later minerogenic horizon appears to represent the Loch Lomond Stadial. Few stratigraphic sequences preserving the complete Devensian Late-glacial-Holocene transition exist in southwest Britain, making the sedimentary archive of the Gordano Valley valuable regionally for reconstructing Late-glacial climate change. © 2007 Springer Science+Business Media B.V

Eosinophil Depletion with Benralizumab for Eosinophilic Esophagitis

Background: Benralizumab is an eosinophil-depleting anti-interleukin-5 receptor α monoclonal antibody. The efficacy and safety of benralizumab in patients with eosinophilic esophagitis are unclear. Methods: In a phase 3, multicenter, double-blind, randomized, placebo-controlled trial, we assigned patients 12 to 65 years of age with symptomatic and histologically active eosinophilic esophagitis in a 1:1 ratio to receive subcutaneous benralizumab (30 mg) or placebo every 4 weeks. The two primary efficacy end points were histologic response (≤6 eosinophils per high-power field) and the change from baseline in the score on the Dysphagia Symptom Questionnaire (DSQ; range, 0 to 84, with higher scores indicating more frequent or severe dysphagia) at week 24. Results: A total of 211 patients underwent randomization: 104 were assigned to receive benralizumab, and 107 were assigned to receive placebo. At week 24, more patients had a histologic response with benralizumab than with placebo (87.4% vs. 6.5%; difference, 80.8 percentage points; 95% confidence interval [CI], 72.9 to 88.8; P<0.001). However, the change from baseline in the DSQ score did not differ significantly between the two groups (difference in least-squares means, 3.0 points; 95% CI, -1.4 to 7.4; P = 0.18). There was no substantial between-group difference in the change from baseline in the Eosinophilic Esophagitis Endoscopic Reference Score, which reflects endoscopic abnormalities. Adverse events were reported in 64.1% of the patients in the benralizumab group and in 61.7% of those in the placebo group. No patients discontinued the trial because of adverse events. Conclusions: In this trial involving patients 12 to 65 years of age with eosinophilic esophagitis, a histologic response (≤6 eosinophils per high-power field) occurred in significantly more patients in the benralizumab group than in the placebo group. However, treatment with benralizumab did not result in fewer or less severe dysphagia symptoms than placebo. (Funded by AstraZeneca; MESSINA ClinicalTrials.gov number, NCT04543409.)