Lungfish Axial Muscle Function and the Vertebrate Water to Land Transition

The role of axial form and function during the vertebrate water to land transition is poorly understood, in part because patterns of axial movement lack morphological correlates. The few studies available from elongate, semi-aquatic vertebrates suggest that moving on land may be powered simply from modifications of generalized swimming axial motor patterns and kinematics. Lungfish are an ideal group to study the role of axial function in terrestrial locomotion as they are the sister taxon to tetrapods and regularly move on land. Here we use electromyography and high-speed video to test whether lungfish moving on land use axial muscles similar to undulatory swimming or demonstrate novelty. We compared terrestrial lungfish data to data from lungfish swimming in different viscosities as well as to salamander locomotion. The terrestrial locomotion of lungfish involved substantial activity in the trunk muscles but almost no tail activity. Unlike other elongate vertebrates, lungfish moved on land with a standing wave pattern of axial muscle activity that closely resembled the pattern observed in terrestrially locomoting salamanders. The similarity in axial motor pattern in salamanders and lungfish suggests that some aspects of neuromuscular control for the axial movements involved in terrestrial locomotion were present before derived appendicular structures.     

Melatonin's Role in Vertebrate Orcadian Rhythms

The circadian secretion of melatonin by the pineal gland and retinae is a direct output of circadian oscillators and of the circadian system in many species of vertebrates. This signal affects a broad array of physiological and behavioral processes, making a generalized hypothesis for melatonin function an elusive objective. Still, there are some common features of melatonin function. First, melatonin biosynthesis is always associated with photoreceptors and/or cells that are embryonically derived from photoreceptors. Second, melatonin frequently affects the perception of the photic environment and has as its site of action structures involved in vision. Finally, melatonin affects overt circadian function at least partially via regulation of the hypothalamic suprachiasmatic nucleus (SCN) or its hofnologues. The mechanisms by which melatonin affects circadian rhythms and other downstream processes are unknown, but they include interaction with a class of membrane-bound receptors that affect intracellular processes through guanosine triphosphate (GTP)-binding protein second messenger systems. Investigation of mechanisms by which melatonin affects its target tissues may unveil basic concepts of neuromodulation, visual system function, and the circadian clock.     

Sleep in birds: lying on the continuum of activity and rest

Abstract

Sleep is highly organized activity which is associated with decreased muscular activity and reduced response to environmental stimuli. The sleep is regulated by both, circadian and homeostatic mechanisms. Sleep patterns can be studied by behavioral assays by observing different sleep behaviors or by neuronal activity such as EEG (electroencephalogram), EOG (electro-oculogram), and EMG (electromyogram). Sleep is organized into non-rapid eye movement (NREM) and rapid eye movement. The sleep pattern in birds are similar to that in mammals, however, few differences such as existence of unihemispheric sleep (UHS) in almost all birds compared to few marine mammals do exist. The UHS results in asymmetry of the brain function measured as slow wave activity (SWA). Several migrants exhibit sleeplessness and they compensate it by NREM. They employ UHS during their migratory flight to remain alert while sleeping and maintain the balance while flying which is advantageous for these birds. Thus, sleep is of fundamental significance for the animal as it lies on the continuum of activity and rest. The present review focuses on some of above mentioned facts about sleep in higher vertebrates particularly in birds.     

The coupled evolution of breathing and locomotion as a game of leapfrog

Because the increase in metabolic rate related to locomotor activity places demands on the cardiorespiratory apparatus, it is not surprising that the evolution of breathing and of locomotion are coupled. As the respiratory faculty becomes more refined, increasingly aerobic life strategies can be explored, and this activity is in turn expedited by a higher-performance respiratory apparatus. This apparent leapfrogging of respiratory and locomotor faculties begins in noncraniate chordates and continues in water-breathing and air-breathing vertebrates. Because both locomotor and cardiorespiratory activities are coordinated in the brain, neurological as well as biochemical coupling is evident. In spite of very different breathing mechanisms in various vertebrate groups, the basic respiratory control mechanisms appear to have been conserved, and respiratory-locomotor coupling is evident in all classes of vertebrates. Hypaxial body wall muscles that were strictly locomotor in fish have respiratory function in amniotes, but some locomotor function remains in all groups.     

Left-right patterning from the inside out: widespread evidence for intracellular control

The field of left-right (LR) patterning--the study of molecular mechanisms that yield directed morphological asymmetries in otherwise symmetrical organisms--is in disarray. On one hand is the undeniably elegant hypothesis that rotary beating of inclined cilia is the primary symmetry-breaking step: they create an asymmetric extracellular flow across the embryonic midline. On the other hand lurk many early symmetry-breaking steps that, even in some vertebrates, precede the onset of ciliary flow. We highlight an intracellular model of LR patterning where gene expression is initiated by physiological asymmetries that arise from subcellular asymmetries (e.g. motor-protein function along oriented cytoskeletal tracks). A survey of symmetry breaking in eukaryotes ranging from protists to vertebrates suggests that intracellular cytoskeletal elements are ancient and primary LR cues. Evolutionarily, quirky effectors like ciliary motion were likely added later in vertebrates. In some species (like mice), developmentally earlier cues may have been abandoned entirely. Late-developing asymmetries pose a challenge to the intracellular model, but early mid-plane determination in many groups increases its plausibility. Multiple experimental tests are possible.     

α-Catenin and IQGAP Regulate Myosin Localization to Control Epithelial Tube Morphogenesis in Dictyostelium

Apical actomyosin activity in animal epithelial cells influences tissue morphology and drives morphogenetic movements during development. The molecular mechanisms leading to myosin II accumulation at the apical membrane and its exclusion from other membranes are poorly understood. We show that in the nonmetazoan Dictyostelium discoideum, myosin II localizes apically in tip epithelial cells that surround the stalk, and constriction of this epithelial tube is required for proper morphogenesis. IQGAP1 and its binding partner cortexillin I function downstream of α- and β-catenin to exclude myosin II from the basolateral cortex and promote apical accumulation of myosin II. Deletion of IQGAP1 or cortexillin compromises epithelial morphogenesis without affecting cell polarity. These results reveal that apical localization of myosin II is a conserved morphogenetic mechanism from nonmetazoans to vertebrates and identify a hierarchy of proteins that regulate the polarity and organization of an epithelial tube in?a simple model organism.     

Budding yeast with human telomeres: a puzzling structure

Telomeres share some common features among eukaryotes, with few exceptions such as the fruit fly Drosophila that uses transposons as telomeres, they consist of G-rich repetitive DNA that is elongated by telomerase and/or alternative pathways depending on recombination. Telomere structure comprises both cis-acting satellite DNA (telomeric DNA) and proteins that interact directly and/or indirectly with the underlying DNA. Telomeric DNAs are surprisingly conserved among the vertebrates and very similar in most eukaryotes, but present some differences in yeast such as Saccharomyces cerevisiae. The telomeric proteins are more variable although the basic mechanisms which control telomere lengthening and capping are very similar, in fact orthologues of the yeast telomeric proteins, which have been studied first, have been identified in other organisms. Here we describe the structure of human telomeres in budding yeast as compared to canonical yeast and mammalian telomeres taking into consideration the more recent findings highlighting the mechanisms that are responsible for chromosome end protection and lengthening, and the role of chromatin organization in telomere function. This yeast represents a model for the study of mammalian telomeres that could be reconstituted step-by-step in all their components, moreover it could be useful for the assembly of mammalian artificial chromosome.     

Ideas in Theoretical Biology - Failure of Anti-Tumor Immunity in Mammals - Evolution of the Hypothesis

Observations on the morphological and functional similarity between embryonic or trophoblast tissues and tumors are very old. Over a period of time many investigators have created different hypotheses on the origin of cancerogenesis or tumor efficiency in relation to the host immune system. Some of these ideas have been rejected but many of them are still current. A presumption of the inefficiency of anti-tumor immunity in mammals due to the high similarity between trophoblast and embryonic cells to tumor cells is very real. The mechanisms for the escape of tumors from the immune response are very similar to the mechanisms for the escape of a fetoplacental unit from the maternal immune response. The similarity between these two mechanisms is so great that any randomness must be banished. At the same time, an incidence of malignant tumors and the types of more frequent tumors in non-mammalian vertebrates is significantly different to that in mammals. Lastly, the mechanisms of anti-tumor immunity in mammals are substantially different from the mechanisms of anti-tumor immunity in other classes of vertebrates. These facts indicate that the immune system of mammals during anti-tumor immune response is tricked by the similarity between tumor cells and trophoblast or other placental cells. From this aspect, our conclusion is that anti-tumor immunity failure in mammals can be defined as an immunoreproductive phenomenon, which is developed under the evolutionary pressure of autoimmunity and reproductive effectiveness.     

Why Can’t Vertebrates Synthesize Trehalose?

The non-reducing disaccharide trehalose is a singular molecule, which has been strictly conserved throughout evolution in prokaryotes (bacteria and archaea), lower eukaryotes, plants, and invertebrates, but is absent in vertebrates and—more specifically—in mammals. There are notable differences regarding the pivotal roles played by trehalose among distantly related organisms as well as in the specific metabolic pathways of trehalose biosynthesis and/or hydrolysis, and the regulatory mechanisms that control trehalose expression genes and enzymatic activities. The success of trehalose compared with that of other structurally related molecules is attributed to its exclusive set of physical properties, which account for its physiological roles and have also promoted important biotechnological applications. However, an intriguing question still remains: why are vertebrates in general, and mammals in particular, unable (or have lost the capacity) to synthesize trehalose? The search for annotated genomes of vertebrates reveals the absence of any functional trehalose synthase gene. Indeed, this is also true for the human genome, which contains, however, two genes encoding for isoforms of the hydrolytic activity (trehalase). Although we still lack a convincing answer, this striking difference might reflect the divergent evolutionary lineages followed by invertebrates and vertebrates. Alternatively, some clinical data point to trehalose as a toxic molecule when stored inside the human body.     

Identification of four highly conserved regions in DNA-PKcs

The gene for the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs) is responsible for severe combined immune deficiency (SCID) and its products associate with Ku70/Ku86 autoantigens, c-Abl, and other factors to exert its roles. Investigations to date suggest that DNA-PKcs comprises several regions which specifically interact with these known and other as yet unidentified factors. Nevertheless, the relationship between the structure and function of the DNA-PKcs molecule is poorly understood. Here we report cloning of the entire DNA-PKcs cDNA from chicken and Xenopus laevis. Comparative study of the DNA-PKcs polypeptides from four different vertebrates revealed at least three novel conserved regions in addition to the carboxyl-terminal region containing the phosphatidylinositol-3 kinase domain. We also demonstrated that the four vertebrates share the common genomic organization between a licensing factor, MCM4, and DNA-PKcs, both of which locate in a head-to-head manner within a few kilobase intervals. These data provide useful clues for the further genetic study of this huge multifunctional enzyme.     

Dual role of cathepsin D: ligand and protease

Cathepsin D is peptidase belonging to the family of aspartic peptidases. Its mostly described function is intracellular catabolism in lysosomal compartments, other physiological effect include hormone and antigen processing. For almost two decades, there have been an increasing number of data describing additional roles imparted by cathepsin D and its pro-enzyme, resulting in cathepsin D being a specific biomarker of some diseases. These roles in pathological conditions, namely elevated levels in certain tumor tissues, seem to be connected to another, yet not fully understood functionality. However, despite numerous studies, the mechanisms of cathepsin D and its precursor's actions are still not completely understood. From results discussed in this article it might be concluded that cathepsin D in its zymogen status has additional function, which is rather dependent on a "ligand-like" function then on proteolytic activity.     

Molecular mechanisms of cardiomyocyte regeneration and therapeutic outlook

Differently from some lower vertebrates, which can completely regenerate their heart, in higher vertebrates cardiac injury generally leads to progressive failure. Induction of cycle re-entry in terminally differentiated cardiomyocytes and stem-cell transplantation are strategies to increase the regenerative potential of the heart. As experimental and clinical studies progress, demonstrating that adult stem-cell administration has a favorable impact on myocardial function, the identification of cardiac stem cells suggests that some endogenous repair mechanisms actually exist in the mammalian heart. However, a deeper understanding of the mechanism that drives cardiomyocyte proliferation and stem-cell-mediated cardiac repair is required to translate such strategies into effective therapies.     

Lactate dehydrogenase from Lampetra planeri is composed of chains of unique type which show intermediate properties between the heart and the muscle isozymes of vertebrates

1. Like other lamprey species, Lampetra planeri displays LDH chains of a single type. Since lampreys are more related to vertebrates than myxines, which do have usual A and B monomers, we suspect that either a gene inactivation or a gene loss occurred in the former group. 2. The characterization of the enzyme gave interesting results. From the standpoint of its affinity for ion exchangers, it behaves as if it is composed of A-type chains. 3. From the standpoint of substrate and product inhibition, it resembles much more closely the B containing isozyme. 4. Since literature reports that the other known single-chained LDH's from lampreys are definitely of the A type, we suggest the possibility that L. planeri enzyme underwent some orthologous evolution which brought it to resemble the heart isozyme.     

Vertebrate Presynaptic Active Zone Assembly: a Role Accomplished by Diverse Molecular and Cellular Mechanisms

Among all the biological systems in vertebrates, the central nervous system (CNS) is the most complex, and its function depends on specialized contacts among neurons called synapses. The assembly and organization of synapses must be exquisitely regulated for a normal brain function and network activity. There has been a tremendous effort in recent decades to understand the molecular and cellular mechanisms participating in the formation of new synapses and their organization, maintenance, and regulation. At the vertebrate presynapses, proteins such as Piccolo, Bassoon, RIM, RIM-BPs, CAST/ELKS, liprin-α, and Munc13 are constant residents and participate in multiple and dynamic interactions with other regulatory proteins, which define network activity and normal brain function. Here, we review the function of these active zone (AZ) proteins and diverse factors involved in AZ assembly and maintenance, with an emphasis on axonal trafficking of precursor vesicles, protein homo- and hetero-oligomeric interactions as a mechanism of AZ trapping and stabilization, and the role of F-actin in presynaptic assembly and its modulation by Wnt signaling.     

Behavioural and functional vestibular disorders after space flight: 2. Fish,amphibians and birds

The review presents data on functional changes in fish, amphibians and birds associated with otolith organ activity after exposure to weightlessness during spaceflight. These data are of importance both for solving some fundamental problems of vestibulology and for practice. In the latter case, lower vertebrates are considered as a convenient and, most importantly, adequate model to unravel the mechanisms of vestibular disorders in humans. Analysis of the experimental results shows that weightlessness exerts no substantial effect on the formation and functional state of the otolith system in embryos of fish, amphibians and birds developing during spaceflight. Moreover, they even promote faster embryonic development of fish and amphibians as shown for mammalian fetuses. The experiments show that both in lower and higher vertebrates weightlessness brings about similar functional and behavioral changes. For example, in fish hatchlings and amphibian tadpoles (without lordosis) the vestibulo-ocular reflex was more pronounced immediately after orbital spaceflight than in control. An analogous alteration in the otolith reflex was observed in most cosmonauts after short-time space missions. In adult terrestrial vertebrates, as well as in humans, immediately after landing there was found a drop in the level of activity and deterioration of the equilibrium function and motor coordination. Another interesting finding was an unusual looping behavior when fish and tadpoles swam in loops post landing. Presumably, unusual motor activity of animals, as well as illusions arising in cosmonauts and astronauts during the transition from 1 to 0 g, have the same background being associated with changes in the stimulation pattern of the otolith organs. Considering the similarity of vestibular responses, the use of animal models seems very promising as allowing different invasive techniques.     

Position matters: variability in the spatial pattern of BMP modulators generates functional diversity

Bone morphogenetic proteins (BMPs) perform a variety of functions during development. Considering a single BMP, what enables its multiple roles in tissues of varied sizes and shapes? What regulates the spatial distribution and activity patterns of the BMP in these different developmental contexts? Some BMP functions require controlling spread of the BMP morphogen, while others require formation of localized, high concentration peaks of BMP activity. Here we review work in Drosophila that describes spatial regulation of the BMP encoded by decapentaplegic (dpp) indifferent developmental contexts. We concentrate on extracellular modulation of BMP function and discuss the mechanisms that generate concentrated peaks of Dpp activity, subdivide territories of different activity levels or regulate spread of the Dpp morphogen from a point source. We compare these findings with data from vertebrates and non‐model organisms to discuss how changes in the regulation of Dpp distribution by extracellular modulators may lead to variability in dpp function in different species. genesis 49:698–718, 2011. © 2011 Wiley‐Liss, Inc.