The Self and the Great Chain of Being: Interview with Robert Bolton

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From organ selector to cell behavior regulator

This is an open-access article licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License.One of the main contributions of Drosophila to the JAK-STAT field is the study of morphogenesis. JAK-STAT signaling controls the formation of many different structures through surprisingly different morphogenetic behaviors that include induction of cell rearrangements, invagination, folding of tissues, modulation of cell shape, and migration. This variability may be explained by the many transcription factors and signaling molecules STAT regulates at early stages of development. But is STAT just acting as an upstream inducer of morphogenesis or does it have a more direct role in controlling cell behaviors? Here we review what is known about how the canonical phosphorylation of STAT contributes to shaping the embryonic and imaginal structures.This work was supported by the Spanish Ministerio de Investigación Ciencia e Innovación, Consolider, the European Regional Development Fund, and Junta de Andalucía.Peer reviewe

Study of the establishment of epithelial polarity: search for new proteins that interact with apkc

Póster presentado al IX Meeting of the Spanish Society for Developmental Biology celebrado en Granada del 12 al 14 de noviembre de 2012.A key issue in developmental biology is the relationship between cell polarity and signal transduction pathways. Most eukaryotic cells are polarized with an asymmetric distribution of molecules and organelles resulting in different functional regions required for cell physiology. The control of this polarity in space and time is essential to coordinate changes in cell morphology with proliferation and morphogenetic movements required for the development of the organism. This control is carried out by signalling pathways, which in many cases are regulated by the subcellular localization of their components. In fact, there is a close relationship between polarity and the control of cell proliferation, since many receptors of intercellular communication pathways that regulate proliferation are located and activated in specific domains of the plasma membrane. Therefore, the understanding of the signalling pathways‐cell polarity relationship is crucial for the knowledge of how signals are integrated to induce morphogenesis but also how are modified in aberrant processes as those occurring in cancer. The atypical protein kinase C (aPKC) is a crucial protein in the cell polarity establishment or maintenance and also can participate in many other processes in the cell. aPKC has an enzymatic activity and can regulate different signaling pathways in the cell. In all these processes aPKC interact, depending on the process, with different regulators and modifies different substrates. In addition, aPKC is an oncogene. To understand how cell polarity is established, maintained and modified and also how this polarity can regulate signalling processes we have focused on to find out new proteins that interact with aPKC.Peer Reviewe

Static range of motion of the first metatarsal in the sagittal and frontal planes

The first metatarsal and medial cuneiform form an important functional unit in the foot, called “first ray”. The first ray normal range of motion (ROM) is difficult to quantify due to the number of joints that are involved. Several methods have previously been proposed. Controversy exists related to normal movement of the first ray frontal plane accompanying that in the sagittal plane. The objective of this study was to investigate the ROM of the first ray in the sagittal and frontal planes in normal feet. Anterior-posterior radiographs were done of the feet of 40 healthy participants with the first ray in a neutral position, maximally dorsiflexed and maximally plantarflexed. They were digitalized and the distance between the tibial malleolus and the intersesamoid crest in the three positions mentioned was measured. The rotation of the first ray in these three positions was measured. A polynomic function that fits a curve describing the movement observed in the first ray was obtained using the least squares method. ROM of the first ray in the sagittal plane was 6.47 (SD 2.59) mm of dorsiflexion and 6.12 (SD 2.55) mm of plantarflexion. ROM in the frontal plane was 2.69 (SD 4.03) degrees of inversion during the dorsiflexion and 2.97 (SD 2.72) degrees during the plantarflexion. A second-degree equation was obtained, which represents the movement of the first ray. Passive dorsiflexion and plantarflexion of the first ray were accompanied by movements in the frontal plane: 0.45 degrees of movement were produced in the frontal plane for each millimeter of displacement in the sagittal plane. These findings might be useful for the future design of instruments for clinically quantifying first ray mobility

Forces shaping a Hox morphogenetic gene network

The Abdominal-B selector protein induces organogenesis of the posterior spiracles by coordinating an organ-specific gene network. The complexity of this network begs the questions of how it originated and what selective pressures drove its formation. Given that the network likely formed in a piecemeal fashion, with elements recruited sequentially, we studied the consequences of expressing individual effectors of this network in naive epithelial cells.We found that, with exception of the Crossveinless-c (Cv-c) Rho GTPase-activating protein, most effectors exert little morphogenetic effect by themselves. In contrast, Cv-c expression causes cell motility and downregulates epithelial polarity and cell adhesion proteins. These effects differ in cells endogenously expressing Cv-c, which have acquired compensatory mechanisms. In spiracle cells, the down-regulation of polarity and E-cadherin expression caused by Cv-c-induced Rho1 inactivation are compensated for by the simultaneous spiracle up-regulation of guanine nucleotide exchange factor (GEF) proteins, cell polarity, and adhesion molecules. Other epithelial cells that have coopted Cv-c to their morphogenetic gene networks are also resistant to Cv-c's deleterious effects. We propose that cooption of a novel morphogenetic regulator to a selector cascade causes cellular instability, resulting in strong selective pressure that leads that same cascade to recruitmolecules that compensate it. This experimental-based hypothesis proposes how the frequently observed complex organogenetic gene networks are put together.This work was supported by the Spanish Ministerio de Investigación Ciencia e Innovación, Consolider, the European Regional Development Fund, and the Junta de Andalucía.Peer Reviewe

Suicide: A Spiritual Perspective

Throughout history, suicide has evoked a remarkably broad range of reactions—from perplexity and condemnation, to glorification and empathy. Many have tried to understand this phenomenon through the lens of psychology, psychiatry, sociology, and anthropology, but much still seems to be amiss. A key factor in our current unprecedented mental health crisis is the undiagnosed impact of modernism and post-modernism; in other words, how has the loss of the sacred contributed to the present-day alienation from ourselves, each other, and the earth? It is only through a fully integrated “science of the soul”—informed by metaphysics and the spiritual wisdom traditions of humanity—that we can, not only better understand suicide, but be properly equipped to avert tragic outcomes