Comparative proteome and peptidome analysis of the cephalic fluid secreted by Arapaima gigas (Teleostei: Osteoglossidae) during and outside parental care

Parental investment in Arapaima gigas includes nest building and guarding, followed by a care provision when a cephalic fluid is released from the parents’ head to the offspring. This fluid has presumably important functions for the offspring but so far its composition has not been characterised. In this study the proteome and peptidome of the cephalic secretion was studied in parental and non-parental fish using capillary electrophoresis coupled to mass spectrometry (CE-MS) and GeLC-MS/MS analyses. Multiple comparisons revealed 28 peptides were significantly different between males and parental males (PC-males), 126 between females and parental females (PC-females), 51 between males and females and 9 between PC-males and PC-females. Identification revealed peptides were produced in the inner ear (pcdh15b), eyes (tetraspanin and ppp2r3a), central nervous system (otud4, ribeye a, tjp1b and syn1) among others. A total of 422 proteins were also identified and gene ontology analysis revealed 28 secreted extracellular proteins. From these, 2 hormones (prolactin and stanniocalcin) and 12 proteins associated to immunological processes (serotransferrin, α-1-antitrypsin homolog, apolipoprotein A-I, and others) were identified. This study provides novel biochemical data on the lateral line fluid which will enable future hypotheses-driven experiments to better understand the physiological roles of the lateral line in chemical communication

Pharmacologic Management of Advanced Cervical Cancer: Antiangiogenesis Therapy and Immunotherapeutic Considerations

As a consequence of disparities in access to and utilization of preventative healthcare, the incidence and death rates from cervical cancer remain substantial in the face of indisputable evidence that screening saves lives. While disparities persist, there will be an urgent need for research into the treatment of advanced forms of this disease. In this review, we explore the evolution of the treatment of metastatic, recurrent, and persistent cervical cancer from cytotoxic agents to targeted therapy. We discuss why targeted therapies are unlikely to produce sustained responses alone but may be more successful in combination with immunotherapies. We also provide a rationale for the potential next phase in treatment of this challenging disease—combined therapy with antiangiogenic agents and immune checkpoint inhibitors. In doing so, we highlight recent paradigm shifts within cancer therapeutics, including the shift in focus from the tumor cell itself to the tumor microenvironment, and from stimulating the immune system to inhibiting the inhibitors of an adequate immune response

Principles driving the spatial organization of Rho GTPase signaling at synapses

The Rho proteins play critical roles in numerous aspects of neuronal development, and mutations in their regulators (GEFs and GAPs) and effectors underlie multiple neurodevelopmental and neurological disorders. How Rho GTPase-mediated signaling can have a hand in regulating so many different neurobiological processes remains a challenging question. An emerging theme is that GAPs and GEFs, through their spatial/temporal regulation and/or through additional protein-protein interactions, cooperate in making connections between upstream signals and the downstream signaling output, engaging distinct effector proteins. This chapter focuses on recent evidence illustrating distinct modes of regulation and specialized roles of Rho regulators particularly in the context of synaptic structure, function, and plasticity, and how their dysregulation affects behavioral processes and contributes to disease. © 2014 Springer-Verlag Wien. All rights reserved