Genome sequence of the emerging pathogen Aeromonas caviae

Aeromonas caviae is a Gram-negative, motile and rod-shaped facultative anaerobe that is increasingly being recognized as a cause of diarrhea in children. Here we present the first genome sequence of an A. caviae strain that was isolated as the sole pathogen from a child with profuse diarrhea.     

Evidence for the localization of the Arabidopsis cytokinin receptors AHK3 and AHK4 in the endoplasmic reticulum

Cytokinins are hormones that are involved in various processes of plant growth and development. The model of cytokinin signalling starts with hormone perception through membrane-localized histidine kinase receptors. Although the biochemical properties and functions of these receptors have been extensively studied, there is no solid proof of their subcellular localization. Here, cell biological and biochemical evidence for the localization of functional fluorophor-tagged fusions of Arabidopsis histidine kinase 3 (AHK3) and 4 (AHK4), members of the cytokinin receptor family, in the endoplasmic reticulum (ER) is provided. Furthermore, membrane-bound AHK3 interacts with AHK4 in vivo. The ER localization and putative function of cytokinin receptors from the ER have major impacts on the concept of cytokinin perception and signalling, and hormonal cross-talk in plants.     

Human Endometrial Extracellular Vesicles Functionally Prepare Human Trophectoderm Model for Implantation: Understanding Bidirectional Maternal‐Embryo Communication

Embryo implantation into maternal endometrium is critical for initiation and establishment of pregnancy, requiring developmental synchrony between endometrium and blastocyst. However, factors regulating human endometrial–embryo cross talk and facilitate implantation remain largely unknown. Extracellular vesicles (EVs) are emerging as important mediators of this process. Here, a trophectoderm spheroid‐based in vitro model mimicking the pre‐implantation human embryo is used to recapitulate important functional aspects of blastocyst implantation. Functionally, human endometrial EVs, derived from hormonally treated cells synchronous with implantation, are readily internalized by trophectoderm cells, regulating adhesive and invasive capacity of human trophectoderm spheroids. To gain molecular insights into mechanisms underpinning endometrial EV‐mediated enhancement of implantation, quantitative proteomics reveal critical alterations in trophectoderm cellular adhesion networks (cell adhesion molecule binding, cell–cell adhesion mediator activity, and cell adherens junctions) and metabolic and gene expression networks, and the soluble secretome from human trophectodermal spheroids. Importantly, transfer of endometrial EV cargo proteins to trophectoderm to mediate changes in trophectoderm function is demonstrated. This is highlighted by correlation among endometrial EVs, the trophectodermal proteome following EV uptake, and EV‐mediated trophectodermal cellular proteome, important for implantation. This work provides an understanding into molecular mechanisms of endometrial EV‐mediated regulation of human trophectoderm functions—fundamental in understanding human endometrium–embryo signaling during implantation.     

Monovalent TNF receptor 1-selective antibody with improved affinity and neutralizing activity

Selective inhibition of tumor necrosis factor (TNF) signaling through the proinflammatory axis of TNF-receptor 1 (TNFR1) while leaving pro-survival and regeneration-promoting signals via TNFR2 unaffected is a promising strategy to circumvent limitations of complete inhibition of TNF action by the approved anti-TNF drugs. A previously developed humanized antagonistic TNFR1-specific antibody, ATROSAB, showed potent inhibition of TNFR1-mediated cellular responses. Because the parental mouse antibody H398 possesses even stronger inhibitory potential, we scrutinized the specific binding parameters of the two molecules and revealed a faster dissociation of ATROSAB compared to H398. Applying affinity maturation and re-engineering of humanized variable domains, we generated a monovalent Fab derivative (13.7) of ATROSAB that exhibited increased binding to TNFR1 and superior inhibition of TNF-mediated TNFR1 activation, while lacking any agonistic activity even in the presence of cross-linking antibodies. In order to improve its pharmacokinetic properties, several Fab13.7-derived molecules were generated, including a PEGylated Fab, a mouse serum albumin fusion protein, a half-IgG with a dimerization-deficient Fc, and a newly designed Fv-Fc format, employing the knobs-into-holes technology. Among these derivatives, the Fv13.7-Fc displayed the best combination of improved pharmacokinetic properties and antagonistic activity, thus representing a promising candidate for further clinical development.     

Enzymatic and detrital influences on the structure, function, and dynamics of spatially-explicit model ecosystems

We developed agent-based models patterned after the equation-based models developed by Schimel and Weintraub (Soil Biol Biochem 35:549–563, 2003) to explore the influence of microbial-derived extracellular enzymes on carbon (C) dynamics. The models featured spatial arrangements of detritus as either randomly-spaced particles (rain) or as root-like structures (root), detritus input intervals (continuous vs. pulsed) and rates (0–5,000 units in 500 unit intervals), trophic structures (presence or absence of predators preying on microbes), and extracellular enzymes with different half-lives (1, 10, 100, and 1,000 time steps). We studied how these features affected C dynamics and model persistence (no extinctions). Models without predators were more likely to persist than those with predators, and their C dynamics could be explained with energetics-based arguments. When predators were present, two of the four model configurations—root-continuous and rain-pulsed—were more likely to persist. The root-continuous models were more likely to persist at lower detritus input rates (500–3,500 units), while the rain-pulsed models were more likely to persist at intermediate detritus input rates (2,000–3,500 units). For both these model configurations, shorter extracellular enzyme half-lives increased the likelihood of persistence. Consistent with the results of Schimel and Weintraub (Soil Biol Biochem 35:549–563, 2003), C dynamics was governed by extracellular enzyme production activity and loss. Our results demonstrated that extracellular enzyme control of C dynamics depends on the spatial arrangement of resources, the input rate and input intervals of detritus and trophic structure.     

A moving–resting process with an embedded Brownian motion for animal movements

Animal movements are of great importance in studying home ranges, migration routes, resource selection, and social interactions. The Global Positioning System provides relatively continuous animal tracking over time and long distances. Nevertheless, the continuous trajectory of an animal’s movement is usually only observed at discrete time points. Brownian bridge models have been used to model movement of an animal between two observed locations within a reasonably short time interval. Assuming that animals are in perpetual motion, these models ignore inactivity such as resting or sleeping. Using the latest developments in applied probability, we propose a moving–resting process model where an animal is assumed to alternate between a moving state, during which it moves in a Brownian motion, and a resting state, during which it does not move. Theoretical properties of the process are studied as a first step towards more realistic models for animal movements. Analytic expressions are derived for the distribution of one increment and two consecutive increments, and are validated with simulations. The induced bridge model conditioning on the starting and end points is used to compute an animal’s probability of occurrence in an observation area during the time of observation, which has wide applications in wildlife behavior research.