Characterization of human Sec16B: indications of specialized, non-redundant functions

The endoplasmic reticulum (ER) represents the entry point into the secretory pathway and from here newly synthesized proteins and lipids are delivered to the Golgi. The selective cargo export from the ER is mediated by COPII-assembly at specific sites of the ER, the so-called transitional ER (tER). The peripheral membrane protein Sec16, first identified in yeast, localizes to transitional ER and plays a key role in organization of these sites. Sec16 defines the tER and is thought to act as a scaffold for the COPII coat assembly. In humans two isoforms of Sec16 are present, the larger Sec16A and the smaller Sec16B. Nevertheless, the functional differences between the two isoforms are ill-defined. Here we describe characterization of the localization and dynamics of Sec16B relative to Sec16A, provide evidence that Sec16B is likely a minor or perhaps specialized form of Sec16, and that it is not functionally redundant with Sec16A

Abnormal Placental Development and Early Embryonic Lethality in EpCAM-Null Mice

BACKGROUND: EpCAM (CD326) is encoded by the tacstd1 gene and expressed by a variety of normal and malignant epithelial cells and some leukocytes. Results of previous in vitro experiments suggested that EpCAM is an intercellular adhesion molecule. EpCAM has been extensively studied as a potential tumor marker and immunotherapy target, and more recent studies suggest that EpCAM expression may be characteristic of cancer stem cells. METHODOLOGY/PRINCIPAL FINDINGS: To gain insights into EpCAM function in vivo, we generated EpCAM -/- mice utilizing an embryonic stem cell line with a tacstd1 allele that had been disrupted. Gene trapping resulted in a protein comprised of the N-terminus of EpCAM encoded by 2 exons of the tacstd1 gene fused in frame to betageo. EpCAM +/- mice were viable and fertile and exhibited no obvious abnormalities. Examination of EpCAM +/- embryos revealed that betageo was expressed in several epithelial structures including developing ears (otocysts), eyes, branchial arches, gut, apical ectodermal ridges, lungs, pancreas, hair follicles and others. All EpCAM -/- mice died in utero by E12.5, and were small, developmentally delayed, and displayed prominent placental abnormalities. In developing placentas, EpCAM was expressed throughout the labyrinthine layer and by spongiotrophoblasts as well. Placentas of EpCAM -/- embryos were compact, with thin labyrinthine layers lacking prominent vascularity. Parietal trophoblast giant cells were also dramatically reduced in EpCAM -/- placentas. CONCLUSION: EpCAM was required for differentiation or survival of parietal trophoblast giant cells, normal development of the placental labyrinth and establishment of a competent maternal-fetal circulation. The findings in EpCAM-reporter mice suggest involvement of this molecule in development of vital organs including the gut, kidneys, pancreas, lungs, eyes, and limbs

The genome of the sea urchin Strongylocentrotus purpuratus

We report the sequence and analysis of the 814-megabase genome of the sea urchin Strongylocentrotus purpuratus, a model for developmental and systems biology. The sequencing strategy combined whole-genome shotgun and bacterial artificial chromosome (BAC) sequences. This use of BAC clones, aided by a pooling strategy, overcame difficulties associated with high heterozygosity of the genome. The genome encodes about 23,300 genes, including many previously thought to be vertebrate innovations or known only outside the deuterostomes. This echinoderm genome provides an evolutionary outgroup for the chordates and yields insights into the evolution of deuterostomes

Transients drive the demographic dynamics of plant populations in variable environments.

This is the final version of the article. Available from the publisher via the DOI in this record.The dynamics of structured plant populations in variable environments can be decomposed into the 'asymptotic' growth contributed by vital rates, and 'transient' growth caused by deviation from stable stage structure.We apply this framework to a large, global data base of longitudinal studies of projection matrix models for plant populations. We ask, what is the relative contribution of transient boom and bust to the dynamic trajectories of plant populations in stochastic environments? Is this contribution patterned by phylogeny, growth form or the number of life stages per population and per species?We show that transients contribute nearly 50% or more to the resulting trajectories, depending on whether transient and stable contributions are partitioned according to their absolute or net contribution to population dynamics.Both transient contributions and asymptotic contributions are influenced heavily by the number of life stages modelled. We discuss whether the drivers of transients should be considered real ecological phenomena, or artefacts of study design and modelling strategy. We find no evidence for phylogenetic signal in the contribution of transients to stochastic growth, nor clear patterns related to growth form. We find a surprising tendency for plant populations to boom rather than bust in response to temporal changes in vital rates and that stochastic growth rates increase with increasing tendency to boom. Synthesis. Transient dynamics contribute significantly to stochastic population dynamics but are often overlooked in ecological and evolutionary studies that employ stochastic analyses. Better understanding of transient responses to fluctuating population structure will yield better management strategies for plant populations, and better grasp of evolutionary dynamics in the real world.Funded by: Natural Environment Research Council. Grant Number: NE/L007770/1, European Social Fund, MaxNetAging Research School, Max Planck Institute for Demographic Research, Max Planck Odense Center for Researc

Divergent demographic strategies of plants in variable environments

This is the author accepted manuscript. The final version is available from Springer Nature via the DOI in this record.One of the best-supported patterns in life history evolution is that organisms cope with environmental fluctuations by buffering their most important vital rates against them. This demographic buffering hypothesis is evidenced by a tendency for temporal variation in rates of survival and reproduction to correlate negatively with their contribution to fitness. Here, we show that widespread evidence for demographic buffering can be artefactual, resulting from natural relationships between the mean and variance of vital rates. Following statistical scaling, we find no significant tendency for plant life histories to be buffered demographically. Instead, some species are buffered, whereas others have labile life histories with higher temporal variation in their more important vital rates. We find phylogenetic signal in the strength and direction of variance–importance correlations, suggesting that clades of plants are prone to being either buffered or labile. Species with simple life histories are more likely to be demographically labile. Our results suggest important evolutionary nuances in how species deal with environmental fluctuations.This work was funded by the Natural Environment Research Council (NERC) UK, grant NE/L007770/1, and supported by NERC IOF grant NE/N006798/1. T.H.G.E. is funded by NERC Fellowship NE/J018163/1

A new technique to improve tissue grip and contact force in arthroscopic capsulolabral repair: the MIBA stitch.

The success of anatomic repair of Bankart lesion diminishes in the presence of a capsule stretching and/or attenuation is reported in a variable percentage of patients with a chronic gleno-humeral instability. We introduce a new arthroscopic stitch, the MIBA stitch, designed with a twofold aim: to improve tissue grip to reduce the risk of soft tissue tear, particularly cutting through capsular-labral tissue, to and address capsule-labral detachment and capsular attenuation using a double loaded suture anchor. This stitch is a combination of horizontal mattress stitch passing through the capsular-labral complex in a "south-to-north" direction and an overlapping single vertical suture passing through the capsule and labrum in a "east-to-west" direction. The mattress stitch is tied before the vertical stitch in order to reinforce the simple vertical stitch, improving grip and contact force between capsular-labral tissue and glenoid bone