Editorial on Special Issue "Marine Gels".

The ocean is a complex polymer solution [...].

Marine Biopolymer Dynamics, Gel Formation, and Carbon Cycling in the Ocean.

Much like our own body, our planet is a macroscale dynamic system equipped with a complex set of compartmentalized controls that have made life and evolution possible on earth. Many of these global autoregulatory functions take place in the ocean; paramount among those is its role in global carbon cycling. Understanding the dynamics of organic carbon transport in the ocean remains among the most critical, urgent, and least acknowledged challenges to modern society. Dissolved in seawater is one of the earth's largest reservoirs of reduced organic carbon, reaching ~700 billion tons. It is composed of a polydisperse collection of marine biopolymers (MBP), that remain in reversible assembled↔dissolved equilibrium forming hydrated networks of marine gels (MG). MGs are among the least understood aspects of marine carbon dynamics. Despite the polymer nature of this gigantic pool of material, polymer physics theory has only recently been applied to study MBP dynamics and gel formation in the ocean. There is a great deal of descriptive phenomenology, rich in classifications, and significant correlations. Still missing, however, is the guide of robust physical theory to figure out the fundamental nature of the supramolecular interactions taking place in seawater that turn out to be critical to understanding carbon transport in the ocean.

Supramolecular dynamics of mucus.

Our purpose here is not to address specific issues of mucus pathology, but to illustrate how polymer networks theory and its remarkable predictive power can be applied to study the supramolecular dynamics of mucus. Avoiding unnecessary mathematical formalization, in the light of available theory, we focus on the rather slow progress and the still large number of missing gaps in the complex topology and supramolecular dynamics of airway mucus. We start with the limited information on the polymer physics of respiratory mucins to then converge on the supramolecular organization and resulting physical properties of the mucus gel. In each section, we briefly discuss progress on the subject, the uncertainties associated with the established knowledge, and the many riddles that still remain.

Marine microgels.

The ocean plays a critical role in global carbon cycling: it handles half of the global primary production, yielding the world's largest stock of reduced organic carbon (ROC) that supports one of the world's largest biomasses. However, the mechanisms whereby ROC becomes mineralized remain unresolved. This review focuses on laboratory and field observations that dissolved organic carbon (DOC) self-assembles, forming self-assembled microgels (SAGs). Self-assembly has approximately10% yield, generating an estimated global seawater SAG budget of approximately 10(16) g C. Transects at depths of 10-4,000 m reveal concentrations of approximately 10(6) to approximately 3 x 10(12) SAG L(-1), respectively, forming an estimated ROC stock larger than the global marine biomass. Because hydrogels have approximately 1% solids (10 g L(-1)), whereas seawater DOC reaches approximately 10(-3) g L(-1), SAGs contain approximately 10(4) more bacterial substrate than seawater. Thus, microgels represent an unsuspected and huge micron-level ocean patchiness that could profoundly influence the passage of DOC through the microbial loop, with ramifications that may scale to global cycles of bioactive elements.

Nucleotide-mediated airway clearance.

A thin layer of airway surface liquid (ASL) lines the entire surface of the lung and is the first point of contact between the lung and the environment. Surfactants contained within this layer are secreted in the alveolar region and are required to maintain a low surface tension and to prevent alveolar collapse. Mucins are secreted into the ASL throughout the respiratory tract and serve to intercept inhaled pathogens, allergens and toxins. Their removal by mucociliary clearance (MCC) is facilitated by cilia beating and hydration of the ASL by active ion transport. Throughout the lung, secretion, ion transport and cilia beating are under purinergic control. Pulmonary epithelia release ATP into the ASL which acts in an autocrine fashion on P2Y(2) (ATP) receptors. The enzymatic network describes in Chap. 2 then mounts a secondary wave of signaling by surface conversion of ATP into adenosine (ADO), which induces A(2B) (ADO) receptor-mediated responses. This chapter offers a comprehensive description of MCC and the extensive ramifications of the purinergic signaling network on pulmonary surfaces.

Unpacking a gel-forming mucin: a view of MUC5B organization after granular release.

Gel-forming mucins are the largest complex glycoprotein macromolecules in the body. They form the matrix of gels protecting all the surface epithelia and are secreted as disulfide-bonded polymeric structures. The mechanisms by which they are formed and organized within cells and thereafter released to form mucus gels are not understood. In particular, the initial rate of expansion of the mucins after release from their secretory granules is very rapid (seconds), but no clear mechanism for how it is achieved has emerged. Our major interest is in lung mucins, but most particularly in MUC5B, which is the major gel-forming mucin in mucus, and which provides its major protective matrix. In this study, using OptiPrep density gradient ultracentrifugation, we have isolated a small amount of a stable form of the recently secreted and expanding MUC5B mucin, which accounts for less than 2% of the total mucin present. It has an average mass of approximately 150 x 10(6) Da and size Rg of 150 nm in radius of gyration. In transmission electron microscopy, this compact mucin has maintained a circular structure that is characterized by flexible chains connected around protein-rich nodes as determined by their ability to bind colloidal gold. The appearance indicates that the assembled mucins in a single granular form are organized around a number of nodes, each attached to four to eight subunits. The organization of the mucins in this manner is consistent with efficient packing of a number of large heavily glycosylated monomers while still permitting their rapid unfolding and hydration. For the first time, this provides some insight into how the carbohydrate regions might be organized around the NH(2)- and COOH-terminal globular protein domains within the granule and also explains how the mucin can expand so rapidly upon its release.

Marine biopolymer self-assembly: implications for carbon cycling in the ocean.

Dissolved organic matter is the largest reservoir of reduced carbon in the ocean and is primarily composed of small biopolymers. It is a critical substrate for the microbial community and plays a pivotal role in global carbon cycling.

Mechanisms of signal transduction in photo-stimulated secretion in Phaeocystis globosa.

Phaeocystis globosa, a leading agent in marine carbon cycling, releases its photosynthesized biopolymers via regulated exocytosis. Release is elicited by blue light and relayed by a characteristic cytosolic Ca(2+) signal. However, the source of Ca(2+) in these cells has not been established. The present studies indicate that Phaeocystis' secretory granules work as an intracellular Ca(2+) oscillator. Optical tomography reveals that photo-stimulation induces InsP(3)-triggered periodic lumenal [Ca(2+)] oscillations in the granule and corresponding out-of-phase cytosolic oscillations of [Ca(2+)] that trigger exocytosis. This Ca(2+) dynamics results from an interplay between the intragranular polyanionic matrix, and two Ca(2+)-sensitive ion channels located on the granule membrane: an InsP(3)-receptor-Ca(2+) channel, and an apamin-sensitive K(+) channel.

InsP3 signaling induces pulse-modulated Ca2+ signals in the nucleus of airway epithelial ciliated cells.

The phenomenology of nuclear Ca(2+) dynamics has experienced important progress revealing the broad range of cellular processes that it regulates. Although several agonists can mobilize Ca(2+) from storage in the nuclear envelope (NE) to the intranuclear compartment (INC), the mechanisms of Ca(2+) signaling in the nucleus still remain uncertain. Here we report that the NE/INC complex can function as an inositol-1,4,5-trisphosphate (InsP(3))-controlled Ca(2+) oscillator. Thin optical sectioning combined with fluorescent labeling of Ca(2+) probes show in cultured airway epithelial ciliated cells that ATP can trigger periodic oscillations of Ca(2+) in the NE ([Ca(2+)](NE)) and corresponding pulses of Ca(2+) release to the INC. Identical results were obtained in InsP(3)-stimulated isolated nuclei of these cells. Our data show that [Ca(2+)](NE) oscillations and Ca(2+) release to the INC result from the interplay between the Ca(2+)/K(+) ion-exchange properties of the intralumenal polyanionic matrix of the NE and two Ca(2+)-sensitive ion channels-an InsP(3)-receptor-Ca(2+) channel and an apamin-sensitive K(+) channel. A similar Ca(2+) signaling system operating under the same functional protocol and molecular hardware controls Ca(2+) oscillations and release in/to the endoplasmic reticulum/cytosol and in/to the granule/cytosol complexes in airway and mast cells. These observations suggest that these intracellular organelles share a remarkably conserved mechanism of InsP(3)-controlled frequency-encoded Ca(2+) signaling.

Secretion in unicellular marine phytoplankton: demonstration of regulated exocytosis in Phaeocystis globosa.

Almost half of the global photosynthetic activity is carried out in the ocean. During blooms, Phaeocystis can fix CO(2) at rates up to 40 g C m(-2) month(-1). Most of this carbon is released as polysaccharides. However, the cellular mechanism whereby this huge amount of organic material is exported into the seawater remains unknown. A vaguely defined process of "exudation" is believed responsible for the release of these biopolymers. Here we report the first demonstration that Phaeocystis globosa does not "exude", but secretes microscopic gels. Secretion is stimulated by blue light (lambda = 470+/-20 nm), and it is transduced by a characteristic intracellular Ca(2+) signal that precedes degranulation. The polysaccharides that form the matrix of these gels remain in condensed phase while stored in secretory vesicles. Upon exocytosis, the exopolymer matrix undergoes a characteristic phase transition accompanied by extensive swelling resulting in the formation of microscopic hydrated gels. Owing to their tangled topology, once released into the seawater, the polymers that make these gels can reptate (axially diffuse), interpenetrate neighboring gels, and anneal them together forming massive mucilage accumulations that are characteristic of Phaeocystis blooms. These gel masses can supply a rich source of microbial substrates, disperse in the seawater, and/or eventually sediment to the ocean floor.

ATP-independent luminal oscillations and release of Ca2+ and H+ from mast cell secretory granules: implications for signal transduction.

InsP(3) is an important link in the intracellular information network. Previous observations show that activation of InsP(3)-receptor channels on the granular membrane can turn secretory granules into Ca(2+) oscillators that deliver periodic trains of Ca(2+) release to the cytosol (T. Nguyen, W. C. Chin, and P. Verdugo, 1998, Nature, 395:908-912; I. Quesada, W. C. Chin, J. Steed, P. Campos-Bedolla, and P. Verdugo, 2001, BIOPHYS: J. 80:2133-2139). Here we show that InsP(3) can also turn mast cell granules into proton oscillators. InsP(3)-induced intralumenal [H(+)] oscillations are ATP-independent, result from H(+)/K(+) exchange in the heparin matrix, and produce perigranular pH oscillations with the same frequency. These perigranular pH oscillations are in-phase with intralumenal [H(+)] but out-of-phase with the corresponding perigranular [Ca(2+)] oscillations. The low pH of the secretory compartment has critical implications in a broad range of intracellular processes. However, the association of proton release with InsP(3)-induced Ca(2+) signals, their similar periodic nature, and the sensitivity of important exocytic proteins to the joint action of Ca(2+) and pH strongly suggests that granules might encode a combined Ca(2+)/H(+) intracellular signal. A H(+)/Ca(2+) signal could significantly increase the specificity of the information sent by the granule by transmitting two frequency encoded messages targeted exclusively to proteins like calmodulin, annexins, or syncollin that are crucial for exocytosis and require specific combinations of [Ca(2+)] "and" pH for their action.

Oscillations of pH inside the secretory granule control the gain of Ca2+ release for signal transduction in goblet cell exocytosis.

Although Ca2+ plays a critical function in relaying intracellular messages, the role of subcellular organelles in the dynamics of intracellular Ca2+ still remains largely unexplored. We recently demonstrated that secretory granules can signal their own export from the cell by releasing Ca2+ to the cytosol. Oscillations and release of Ca2+ in/from the granule result from the combined action of a Ca2+/K+ ion exchange process that occurs in the granule's matrix, and the sequential activation of two Ca2+-sensitive ion channels: an inositol 1,4,5-trisphosphate receptor Ca2+ channel (InsP3R) and an apamin-sensitive Ca2+-activated K+ channel (ASK(Ca)). The results reported here from studies using isolated mucin granules indicate that intralumenal granular Ca2+ oscillations ([Ca2+]L) and the corresponding cyclical release of Ca2+ to the cytosol induced by InsP3 are accompanied by corresponding intragranular pH(G) oscillations. Our data show that K+-induced unbinding of Ca2+ from the mucin matrix increases as the pH(G) declines. These observations suggest that oscillations of pH(G) can modulate the gain of the Ca2+/K+ ion exchange process, thereby controlling the amplitude of [Ca2+]L oscillations and the granule-cytosol release gradient of [Ca2+].

Arteria cervical transversa: estudio anatómo-quirúrgico / Transverse cervical artery: anatomical and surgical study

La arteria cervical transversa ha sido descrita por diversos autores con varios nombres, asignándole incluso diferente origen. Esta arteria, y debido al avance de la cirugía reparativa en cabeza y cuello que considera colgajos osteomiocutáneos de músculo trapezio y escápula, ha alcanzado considerable importancia por ser el principal vaso arterial de la zona dadora del colgajo. El trabajo realizado en especímenes adultos fijados, aporta una revisión macroscópica de la arteria, señalando las características en cuanto a origen, longitud, diámetro, relaciones, distribución y su aporte al músculo trapezio, considerando su posible desplazamiento en colgajos osteomiocutáneos de esta zona