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Distribution of tyrosine hydroxylase, dopamine, and serotonin in the central nervous system of amphioxus (Branchiostoma lanceolatum): implications for the evolution of catecholamine systems in vertebrates.

To investigate the evolutionary transition that has shaped the catecholaminergic systems of vertebrates, the organization of catecholamine-synthesizing neurons and the nature of the catecholamines were examined in the central nervous system of adult amphioxus (Branchiostoma lanceolatum), a cephalochordate. We isolated a gene transcript encoding tyrosine hydroxylase (TH), the limiting enzyme of catecholamine biosynthesis, and studied its distribution together with that of dopamine and serotonin. Dopamine and TH are found in the same neurons of which they are three separate populations. Two are located in the anterior brain, the first being dorsal and lying in a row and the second being more posterior and lateral. A third population comprising a few dorsal commissural neurons was found in the posterior brain. The anterior dopaminergic cells innervate the ventral commissure of the cephalic vesicle, the hindbrain, and the spinal cord. A serotonin-containing cell group is located in the same plane as the second dopaminergic cell population but is more caudal, marking the probable transition between anterior brain and hindbrain, as deduced from gene expression patterns. The overall distribution of dopaminergic and serotoninergic systems is similar in amphioxus and vertebrate central nervous system and could be an ancestral character of chordates. As assayed by high-performance liquid chromatography and electrochemical detection, significant amounts of dopamine and octopamine, but not of noradrenaline, are present in amphioxus head. This finding is consistent with data obtained from most prostomian species. We conclude that the noradrenergic system is probably an innovation of vertebrates that appeared along with the neural crest and specific hindbrain nuclei.

Amino Acid Sequence↗

A different type of amphibian mesoderm morphogenesis in Ceratophrys ornata.

Ceratophrys ornata, the Argentinean horned frog, has a significantly different pattern of early morphogenesis than does the most studied amphibian, Xenopus laevis. Time-lapse videomicroscopy, scanning electron microscopy, histological sections and lineage tracers have shown that, in C. ornata, some prospective notochord, somite and tailbud mesoderm cells leave the surface epithelium of the archenteron by ingression. After gastrulation, SEM reveals cells with constricted apices and a bottle shape in three zones on the archenteron roof and in a fourth zone around the blastopore. Prospective somitic tissue ingresses first from two lateral zones, followed by ingression of prospective notochord from the medial zone and tailbud mesoderm from the circumblastoporal zone. This is unlike X. laevis, in which no cells with constricted apices are present on the dorsal surface of the archenteron, nor do any cells ingress into the deep mesodermal layers from the surface layer.

Animals↗

Ultrastructural classification of the endocrine cells of the large intestine of the calf. Cytochemical evidence of the presence of Viallis's pre-EC cells.

GEP (Gastro-Entero-Pancreatic) endocrine cells were very numerous in the mucosal layer of the large intestine of the calf. Their frequence appeared to increase towards the distal portions of the gut. Endocrine cells were dispersed among epithelial cells lining intestinal glands and were frequently grouped together. Cellular shape was pyramidal or elongated; the cytoplasm was electron-lucent and contained highly characteristic secretory granules. Six different types of endocrine cells were identified on the basis of the ultrastructural aspect and cytochemical characteristics (silver-reactivity) of their secretory granules: EC, L, PP, A, D1 and D cells. EC and L cells were the most abundant in all localisations. They were especially numerous in the rectum. A subpopulation of EC cells was negative to Masson-Singh's reaction showing that they lack 5-HT. This observation enabled us to refer this latter cellular type to the "pre-EC" cells, described by Vialli as an earlier evolutive step of the EC cells population. Their presence in the calf gut might be linked to its possible "immaturity", due either to the age or to the alimentary diet.

Aging↗

Lattice Boltzmann algorithm to simulate isotropic-nematic emulsions.

We present lattice Boltzmann simulations of the dynamical equations of motion of a drop of isotropic fluid in a nematic liquid crystal solvent, both in the absence and in the presence of an electric field. The coupled equations we solve are the Beris-Edward equations for the dynamics of the tensor order parameter describing the nematic solvent, the Cahn-Hilliard equation for the concentration evolution, and the Navier-Stokes equations for the determination of the instantaneous velocity field. We implement the lattice Boltzmann algorithm to ensure that spurious velocities are close to zero in equilibrium. We first study the effects of the liquid crystal elastic constant, K, anchoring strength, W, and surface tension, sigma, on the shape of the droplet and on the director field texture in equilibrium. We then consider how the drop behaves as the director field is switched by an applied electric field. We also show that the algorithm allows us to follow the motion of a drop of isotropic fluid placed in a liquid crystal cell with a tilted director field at the boundaries.

Journal Article↗

[Prenatal development of human retinal vessels].

Feeding of the retina, whose thickness does not exceed 130 mu km, is possible at the account of chriocapillary diffusion. Should this threshold be topped (approximately by the 3.5th prenatal month), it will result in a relative hypoxia of the uttermost internal strata of the retina, which induces the appearance of new feeding source, i.e. retinal vessels. First, dense cellular steaks of the sequential fusiform cells originating from the visual-stem depth located near the wall of a. hyaloidea emerge in the surface retinal strata. These cells (angioblasts) formed the peripapillary plexus, shaped as a vascular pattern, and represented a non-lumenized prototype, or matrix, of a future capillary network. Later, main arterioles emerged, in the outward direction from them, and after that venules took shape from the above network through a partial reduction of vessels and a redistribution of blood circulation. The second deep capillary stratum was formed rather through a prolongation and "sagging" of the surface capillary loops than through gemmation; it is common for the entire retina and, unlike the surface stratum, is not divided by main arterioles into adjoining segments. By the 8th fetal-life month the evolution of the retinal bloodstream is not entirely completed, though it resembles, to a great extent, a definitive one.

Arterioles↗

Does structural and chemical divergence play a role in precluding undesirable protein interactions?

To understand the evolutionary forces establishing, maintaining, breaking, or precluding protein-protein interactions, a comprehensive data set of protein complexes has been analyzed to examine the overlap between protein interfaces and the most conserved or divergent protein surface areas. The most divergent areas tend to be found predominantly away from protein interfaces, although when found at interfaces, they are associated with specific lack of cross-reactivity between close homologues, like in antibody-antigen complexes. Moreover, the amino acid composition of highly variable regions is significantly different from any other protein surfaces. The variable regions present higher structural plasticity as a result of insertions and deletions, and favor charged over hydrophobic residues, a known strategy to minimize aggregation. This suggests that (1) a rapid rate of mutations at these regions might be continuously altering their properties, making difficult the coadaptation, in shape and chemical complementarity, to potential interacting partners; and (2) the existence of some form of selective pressure for variable areas away from interfaces to accumulate charged residues, perhaps as an evolutionary mechanism to increase solubility and minimize undesirable interactions within the crowded cellular environment. Finally, these results are placed into the context of the aberrant oligomerization of sickle-cell anemia hemoglobin and prion proteins.

Amino Acid Sequence↗

Architecture and evolution of dinoflagellate chromosomes: an enigmatic origin.

Dinoflagellates are a highly diversified group of unicellular protists that present fascinating nuclear features which have intrigued researchers for many years. As examples, a dense nuclear matrix accommodates permanently condensed chromosomes that are composed of fibers organized without histones and nucleosomes in stacked rows of parallel nested arches. The macromolecular chromosome structure corresponds to cholesteric liquid crystals with a constant left-handed twist. RNA acts to maintain the chromosome structure. Whole mounted chromosomes have a left-handed screw-like configuration with coils which progressively increase their pitch. This helical arrangement seems to be the result of a couple of narrow strands coiling together. Chromosomes do not show Q, G and C banding patterns. However, a roughly spherical differentiated upper end (primitive kinetochore?) and two differentiated coiling regions, the upper one composed of two to three coils where a couple of sister strands run together and parallel to each other, and the lower one where sister strands run out of phase by 180 degrees angular difference along the immediate next turns, can be distinguished. The chromosome segregation into two daughter chromatids begins at the telomere that attaches to the nuclear envelope, follows along the chromosome axis constituting first a Y-shaped and afterwards a V-shaped chromosome, which packs the newly synthesized DNA inside the "old" chromosome. Dividing chromosomes remain highly condensed, and the diameters of the new chromatids and the undivided chromosome are similar, but the number of arches is twice as large in G1 as in G2. The nuclear envelope remains through the cell cycle and shows spindle fibers, which penetrate intranuclear cytoplasmic channels during mitosis constituting an extra nuclear spindle. These and other cytogenetic features suggest that dinoflagellates are a group of enigmatic protists, unique and different from the usual eukaryotes. In contrast, DNA sequence studies propose that dinoflagellates are true eukaryotes, closely related to Apicomplexa, and ciliates (Alveolata), suggesting that the unusual features of chromosome and nuclear organization are not primitive but derived characters. Nevertheless, dinoflagellates have reached enigmatic specific nuclear and chromosome solutions, extremely far from those of other living beings.

Animals↗

An intracellular actin motor in bacteria?

Actin performs structural as well as motor-like functions in eukaryotic cells. Orthologues of actin have also been identified in bacteria, where they perform an essential function during cell growth. Bacterial actins are implicated in the maintenance of rod-shaped cell morphology, and appear to form a cytoskeletal structure, localising as helical filaments underneath the cell membrane. Recently, a plasmid-borne actin orthologue has been shown to perform a mitotic-like function during segregation of a plasmid, and chromosomally encoded actin proteins were found to play an important role in chromosome segregation. Based on the findings that actin filaments are dynamic structures in two bacterial species, we propose that actins perform motor functions rather than a purely structural role in bacteria. We suggest that an intracellular motor exists in bacteria that could be derived from an ancestral actin motor that was present in cells early in evolution.

Actins↗

Mitochondrial dynamics and division in budding yeast.

Mitochondria adopt a variety of different shapes in eukaryotic cells, ranging from multiple, small compartments to elaborate tubular networks. The establishment and maintenance of different mitochondrial morphologies depends, in part, on the equilibrium between opposing fission and fusion events. Recent studies in yeast, flies, worms and mammalian cells indicate that three high-molecular-weight GTPases control mitochondrial membrane dynamics. One of these is a dynamin-related GTPase that acts on the outer mitochondrial membrane to regulate fission. Recently, genetic approaches in budding yeast have identified additional components of the fission machinery. These and other new findings suggest a common mechanism for membrane fission events that has been conserved and adapted during eukaryotic evolution.

Cell Cycle↗

Positive selection on a human-specific transcription factor binding site regulating IL4 expression.

A single nucleotide polymorphism in the promoter of the multifunctional cytokine Interleukin 4 (IL4) affects the binding of NFAT, a key transcriptional activator of IL4 in T cells. This regulatory polymorphism influences the balance of cytokine signaling in the immune system, with important consequences-positive and negative-for human health. We determined that the NFAT binding site is unique to humans; it arose by point mutation along the lineage separating humans from other great apes. We show that its frequency distribution among human subpopulations has been shaped by the balance of selective forces on IL4's diverse roles. New statistical approaches, based on parametric and nonparametric comparisons to neutral variants typed in the same individuals, indicate that differentiation among subpopulations at the IL4 promoter polymorphism is too great to be attributed to neutral drift. The allele frequencies of this binding site represent local adaptation to diverse pathogenic challenges; disease states associated with the common derived allele are side-effects of positive selection on other IL4 functions.

Animals↗

Structural, energetic, and functional analysis of a protein-protein interface at distinct stages of affinity maturation.

Due to a paucity of studies that synthesize structural, energetic, and functional analyses of a series of protein complexes representing distinct stages in an affinity maturation pathway, the biophysical basis for the molecular evolution of protein-protein interactions is poorly understood. Here, we combine crystal structures and binding-free energies of a series of variant superantigen (SAG)-major histocompatibility complex (MHC) class II complexes exhibiting increasingly higher affinity to reveal that this affinity maturation pathway is controlled largely by two biophysical factors: shape complementarity and buried hydrophobic surface. These factors, however, do not contribute equivalently to the affinity maturation of the interface, as the former dominates the early steps of the maturation process while the latter is responsible for improved binding in later steps. Functional assays reveal how affinity maturation of the SAG-MHC interface corresponds to T cell activation by SAGs.

Binding Sites↗

A choanoflagellate cGLR-STING pathway reveals evolutionary links between bacterial and animal immunity.

Animal innate immunity evolved from ancient pathways in bacterial anti-phage defense. How bacterial immune components were first acquired and adapted within eukaryotic cells remains poorly understood. Here we identify a complete cGLR-STING signaling axis in choanoflagellates, the closest living relatives of animals, that exhibits a mosaic of features from both bacterial and animal immunity. Comparative genomics reveals choanoflagellate cGLR and STING genes organized in operon-like arrangements reminiscent of bacterial defense loci. Reconstitution of choanoflagellate cGLR-STING signaling in vitro demonstrates that activation occurs through the conserved nucleotide immune signal 2'3'-cGAMP. Structural analysis of a choanoflagellate STING-2'3'-cGAMP complex explains how retention of bacterial-like features in early eukaryotic proteins shapes ligand specificity and receptor activation. We analyze cGLR and STING evolution in unicellular eukaryotes and identify further STING homologs in choanoflagellates and fungi that support additional independent acquisition events. Our results reveal molecular fossils that bridge bacterial and animal immunity and illuminate early eukaryotic immune system evolution.

Journal Article↗

Structure and function in the auditory system: From cochlea to cortex.

This special issue of the Anatomical Record examines the relationship between structure and function in the auditory system. Early anatomical studies defined this relationship on a macroscopic level and described the roles of structures such as the tympanic membrane, ossicular chain, Eustachian tube, and cochlea. As new tools emerged, the microscopic structure of the organ of Corti was described and later the brain stem regions involved in auditory processing were identified. Further technical advances allowed the description of cells within these central auditory regions in both morphological and physiological terms. More recently, studies of the auditory system have employed molecular biological techniques and novel imaging protocols. All these techniques continue to provide important insights into the structure and function of the auditory system on gross, cellular, and molecular levels. This issue expounds on this theme by demonstrating the importance of anatomy, whether the shape of the otic capsule or the sequence of a gene, in determining the function of the system and even the phenotype of the organism. The articles in this issue represent the cutting edge of today's auditory science and look back at the evolution of hearing and balance, as well as forward toward improving cochlear implant outcomes and gene therapies for treating sensorineural hearing loss.

Animals↗

The changing of the guard: Molecular diversity and rapid evolution of beta-defensins.

Defensins are small cationic peptides involved in innate immunity and are components of the first line of defence against invading pathogens. beta-defensins are a subgroup of the defensin family that display a particular cysteine spacing and pattern of intramolecular bonding. These molecules are produced mostly by epithelia lining exposed surfaces and appear to have both antimicrobial and cell signalling functions. The unusually high degree of sequence variation in the mature peptide produced by the paralogous and in some cases orthologous genes implies extensive specialisation and species specific adaptation. Here we review recent functional data that are an important addition to our knowledge of the innate immune response and novel antibiotic design. We also consider the organisation and evolution of the genomic loci harbouring these genes where radical and rapid changes in beta-defensin sequences have been shown to result from the interplay of both positive and negative selection. Consequently these genes provide some unusually clear glimpses of the processes of duplication and specialisation that have shaped the mammalian genome.

Amino Acid Sequence↗

Osteosynthetic titanium mini-plate fixation of composite radial forearm flaps in mandibular reconstruction.

This paper describes the evolution and refinement, over a four-year period, of a simple technique for shaping and stabilising the bony component of a composite radial forearm free flap to reconstruct the mandible following segmental resection for neoplastic disease. The results of reconstruction in 30 consecutive patients are reported. The current method of adapting and stabilising the radial bony strut using a specially designed 32 hole osteosynthetic miniplate is described.

Adult↗

Coevolution of TCR-MHC interactions: conserved MHC tertiary structure is not sufficient for interactions with the TCR.

The specificity for self-MHC that is necessary for T cell function is a consequence of intrathymic selection during which T cell antigen receptors (TCRs) expressed by immature thymocytes are tested for their affinity for self-peptide:self-MHC. The germ-line-encoded segments of the TCR, however, are believed to have an innate specificity for structural features of MHC molecules. We directly tested this hypothesis by generating a transgenic mouse system in which the protein HLA-DM is expressed at the surface of thymic cortical epithelial cells in the absence of classical MHC molecules. The specialized intracellular function of HLA-DM has removed this MHC class II-like protein from the evolutionary forces that have been hypothesized to shape TCR-MHC interactions. Our study shows that a structural mimic of MHC class II is not sufficient to appropriately interact with the TCRs expressed by developing thymocytes. This result emphasizes the unique complementarity of TCR-MHC interactions that are maintained by the evolutionary pressures dictated by positive selection.

Animals↗

Ancient Introgression Explains Mitochondrial Genome Capture and Mitonuclear Discordance Among South American Collared Tropidurus Lizards.

Mitonuclear discordance-evolutionary discrepancies between mitochondrial and nuclear DNA phylogenies-can arise from various factors, including introgression, incomplete lineage sorting, recent or ancient demographic fluctuations, sex-biased dispersal asymmetries, among others. Understanding this phenomenon is crucial for accurately reconstructing evolutionary histories, as failing to account for discordance can lead to misinterpretations of species boundaries, phylogenetic relationships, and historical biogeographic patterns. We investigate the evolutionary drivers of mitonuclear discordance in the Tropidurus spinulosus species group, which contains nine species of lizards inhabiting open tropical and subtropical environments in South America. Using a combination of population genetic and phylogenomic approaches applied to mitochondrial and nuclear data, we identified different instances of gene flow that occurred in ancestral lineages of extant species. Our results point to a complex evolutionary history marked by prolonged isolation between species, demographic fluctuations, and potential episodes of secondary contact with genetic admixture. These conditions likely facilitated mitochondrial genome capture while diluting signals of nuclear introgression. Furthermore, we found no strong evidence supporting incomplete lineage sorting or natural selection as primary drivers of the observed mitonuclear discordance. Therefore, the unveiled patterns are most consistent with neutral demographic processes, coupled with ancient mitochondrial introgression, as the main factors underlying the mismatch between nuclear and mitochondrial phylogenies in this system. Future research could further explore the role of other demographic processes, such as asymmetric sex-biased dispersal, in shaping these complex evolutionary patterns.

Animals↗

MAP kinase pathways: the first twenty years.

The MAP kinases, discovered approximately 20 years ago, together with their immediate upstream regulators, are among the most highly studied signal transduction molecules. This body of work has shaped many aspects of our present views of signal transduction by protein kinases. The effort expended in this area reflects the extensive participation of these regulatory modules in the control of cell fate decisions, i.e., proliferation, differentiation and death, across all eukaryotic phylla and in all tissues of metazoans. The discovery of these kinases is reviewed, followed by a discussion of some of the features of this signaling module that account for its broad impact on cell function and its enormous interest to many investigators.

Animals↗