Hypoxia inhibits the expression of the CCR5 chemokine receptor in macrophages

Hypoxia, a decrease in oxygen tension occurring in pathological tissues, has a profound effect on macrophage functions. Here, we provide the first evidence that hypoxia inhibits CCR5 chemokine receptor expression in mouse macrophages. CCR5 was constitutively expressed in macrophages and upregulated by IFNgamma. Hypoxia downregulated both constitutive and IFNgamma-induced CCR5 mRNA and protein. Reoxygenation of hypoxic cells reverted CCR5 inhibition. CCR5 upregulation by IL-10, LPS, and IL-4 was also antagonized by hypoxia. CCR5 inhibition may be a way to retain/concentrate recruited macrophages at hypoxic sites or a feedback mechanism to control the autocrine activation of macrophages which produce CCR5 ligands.     

Single step recombinant human growth hormone (rhGH) purification from milk by peptide affinity chromatography

Recombinant human growth hormone (rhGH) is used for the treatment of several pathologies, most of them related to growth. Although different expression systems can be used for its production, the milk from transgenic cows is one of the most interesting due to the high rhGH level achieved (5 g/L). We have designed and synthesized short peptides (9 or 10 amino acid long) using Fmoc chemistry and studied their ability to purify rhGH from milk once immobilized on an agarose support. Using spiked milk with the hormone as a sample, rhGH was purified with 88% yield and 92% purity in a single step with a fold purification of 4.5. © 2018 American Institute of Chemical Engineers Biotechnol. Prog., 34:999–1005, 2018     

IL-2 signaling in human monocytes involves the phosphorylation and activation of p59hck

The activating properties of IL-2 and the structure of the IL-2R on human monocytes are well characterized. However, relatively little is known about the biochemical mechanisms involved in IL-2 signal transduction in these cells. We investigated the role of protein tyrosine kinases (PTKs) in the activation of monocytes by IL-2. Incubation of monocytes with the PTK inhibitor herbimycin A (HA) resulted in the dose-dependent suppression of IL-2-induced monocyte tumoricidal activity. This inhibition was rather potent, as a concentration of HA as low as 0.5 microM caused a complete abrogation of cytolytic activity. Furthermore, HA markedly suppressed the ability of IL-2 to induce IL-1 beta, TNF-alpha, IL-6, and IL-8 mRNA expression and protein secretion by monocytes. Anti-phosphotyrosine immunoblotting demonstrated that IL-2 induced a rapid and time-dependent increase in tyrosine phosphorylation of several cellular proteins of molecular masses ranging from 35 to 180 kDa. Interestingly, IL-2 caused a significant up-regulation of the constitutive levels of hck PTK mRNA and protein relative to medium-treated cells as well as an increase in p59hck tyrosine phosphorylation. Finally, we demonstrated by in vitro kinase assay that the specific activity of p59hck PTK was also induced by IL-2 in monocytes. Thus, these data show that the activation of PTKs is required for the triggering of monocyte effector and secretory functions by IL-2 and strongly suggest that p59hck is a key participant in IL-2 signaling in human monocytes.     

Data-Driven Modeling of Intracellular Auxin Fluxes Indicates a Dominant Role of the ER in Controlling Nuclear Auxin Uptake

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Enhancement of hormonal activity with a monoclonal antibody specific to porcine growth hormone

Abstract

The potentiation of the biological effects of recombinant porcine growth hormone (pGH) by immunologic manipulation was investigated. A monoclonal antibody (mAb), designated PS‐7.6, was raised against pGH and repeatedly shown to enhance the responsiveness of hypophysectomized (hypox) rats to pGH. As a result, animals receiving a combination treatment of pGH and mAb PS‐7.6 together gained significantly more weight than those receiving the same doses of pGH alone. The enhancing action of the mAb was a rapid process and its effective doses ranged from 0.1 to 2 mg/injection. The ability of the antibody to augment the hormonal activity persisted beyond the 5‐day treatment period and the differences in net weight gain between treated and control animals remained significant for 28 days. Results from treatment frequency studies further suggested that pGH when complexed with mAb PS‐7.6 required fewer injections and produced a greater efficacy than being administered alone. Therefore, present findings suggest that mAb PS‐7.6 may prove useful for not only improving the efficiency of pGH, but also developing a novel formulation for sustained pGH release.     

Fix your eyes in the space you could reach: neurons in the macaque medial parietal cortex prefer gaze positions in peripersonal space

Interacting in the peripersonal space requires coordinated arm and eye movements to visual targets in depth. In primates, the medial posterior parietal cortex (PPC) represents a crucial node in the process of visual-to-motor signal transformations. The medial PPC area V6A is a key region engaged in the control of these processes because it jointly processes visual information, eye position and arm movement related signals. However, to date, there is no evidence in the medial PPC of spatial encoding in three dimensions. Here, using single neuron recordings in behaving macaques, we studied the neural signals related to binocular eye position in a task that required the monkeys to perform saccades and fixate targets at different locations in peripersonal and extrapersonal space. A significant proportion of neurons were modulated by both gaze direction and depth, i.e., by the location of the foveated target in 3D space. The population activity of these neurons displayed a strong preference for peripersonal space in a time interval around the saccade that preceded fixation and during fixation as well. This preference for targets within reaching distance during both target capturing and fixation suggests that binocular eye position signals are implemented functionally in V6A to support its role in reaching and grasping.     

The Ramachandran plots of glycine and pre-proline

Background  

The Ramachandran plot is a fundamental tool in the analysis of protein structures. Of the 4 basic types of Ramachandran plots, the interactions that determine the generic and proline Ramachandran plots are well understood. The interactions of the glycine and pre-proline Ramachandran plots are not.