Possible Adaptive Value of Endosymbionts to Their Protozoan Hosts1,2

ABSTRACT. It is generally accepted that in symbiotic systems involving algal species as cellular endobionts there is some positive benefit to the host organisms. In this paper special consideration is given to the larger foraminifera, protozoa that serve as very useful model systems for the study of aspects of inter/intracellular integration and adaptation—living, as they do, in nutrient-limited but well illuminated shallow tropical seas and containing endosymbiotic algae in abundance. A considerable amount of information is now available on physiological as well as morphological adaptations of the host species to pigmented protists representing diverse algal divisions (phyla). Brief mention is also made of bacterial endosymbionts of certain ciliates.     

Large-scale insect cell culture.

Significant advances have been made over the past year in our understanding of the protective mechanisms, both fluid-mechanical and biological, of media additives on suspended animal cells. The degree of protection offered by different additives, such as pluronic polyol, appears to be cell-type dependent, varying quite dramatically not only between insect and mammalian cells, but also between different insect cell lines themselves.     

Cyclic nucleotides: the current dilemma!

Significant advances in understanding plant cyclic nucleotide signalling have been made in the past two years. The roles of these molecules in the regulation of ionic channels, defence responses and the apical growth of cells are being uncovered.     

Quantitative phosphoproteomics by mass spectrometry: past, present, and future

Protein phosphorylation-mediated signaling networks regulate much of the cellular response to external stimuli, and dysregulation in these networks has been linked to multiple disease states. Significant advancements have been made over the past decade to enable the analysis and quantification of cellular protein phosphorylation events, but comprehensive analysis of the phosphoproteome is still lacking, as is the ability to monitor signaling at the network level while comprehending the biological implications of each phosphorylation site. In this review we highlight many of the technological advances over the past decade and describe some of the latest applications of these tools to uncover signaling networks in a variety of biological settings. We finish with a concise discussion of the future of the field, including additional advances that are required to link protein phosphorylation analysis with biological insight.     

Cyclooxygenase-2 and prostaglandin signaling in cholangiocarcinoma

Cholangiocarcinoma is a highly malignant epithelial neoplasm arising within the biliary tract and its incidence and mortality is rising. Early diagnosis is difficult and there is presently no effective treatment. Significant progress has been made over the past several years in defining the link between COX-2 and cholangiocarcinogenesis. Selective COX-2 inhibitors have been shown to inhibit cholangiocarcinoma cell growth in vitro and in animal models. However, recently, concerns have been raised about the cardiovascular side effect associated with some COX-2 inhibitors utilized at relatively high dose for antitumor chemoprevention, despite that these inhibitors have a proven safety profile when given as monotherapy to arthritis patients. Therefore, there is an urgent and practical need to develop novel chemopreventive strategy that simultaneously targets COX-2 signaling and other related key molecules in cholangiocarcinogenesis, such as EGFR or utilization of agents inhibiting COX-2 signaling in conjunction with other standard chemotherapy or radiation therapy; these approaches are expected to provide synergistic anti-tumor effect with lesser side effect. In this context, the recently delineated interplay between COX-2-derived PG signaling and other growth-regulatory pathways, such as EGFR, ErbB2, IL-6/GP130, HGF/Met, TGF-beta/Smad, and iNOS is expected to provide important therapeutic implications. This review will summarize the recent advances in understanding the mechanisms for COX-2-derived PG signaling in cholangiocarcinogenesis and focus on the newly unveiled interactions between PG cascade and other key signaling pathways that coordinately regulate cholangiocarcinoma growth. Knowledge on these aspects will help develop more effective therapeutic strategy targeting COX-2 and related key signaling molecules.     

Paleoceanographic changes during the past 1.9 Myr at DSDP Site 238, Central Indian Ocean Basin: Benthic foraminiferal proxies

Deep-sea benthic foraminifera have been quantitatively analyzed in samples (> 125 μm size fraction) from Ocean Drilling Program (ODP) Site 238, to understand paleoceanographic changes in the Central Indian Basin over the past 1.9 Myr. Factor and cluster analyses of the 25 highest-ranked species made it possible to identify five biofacies, characterizing distinct deep-sea environmental settings. The environmental interpretation of each biofacies is based on the ecology of recent deep-sea benthic foraminifera. The benthic faunal record indicates fluctuating deep-sea conditions in environmental parameters including oxygenation, surface productivity and organic food supply. These changes appear to be linked to Indian summer monsoon variability, the main climatic feature of the Indian Ocean region. The benthic assemblages show a major shift at ∼ 0.7 to 0.6 Ma, marked by major turnovers in the relative abundances of species, coinciding with an increased amplitude of glacial cycles. These cycles appear to have influenced low latitude monsoonal climate as well as deep-sea conditions in the Central Indian Ocean Basin.     

Oligonucleotide therapy

Rapid progress in oligonucleotide therapeutics has continued over the past year as major programs established in the past four years have grown and begun to be productive. Important advances were reported in the medicinal chemistry of oligonucleotides and in understanding their pharmacodynamic properties. Significant progress was made in understanding the pharmacokinetic and toxicologic properties of first generation analogs, particularly phosphorothioates and one oligonucleotide, ISIS 2105, entered clinical trials. Additionally, combinatorial approaches designed to identify oligonucleotides that may bind to a variety of targets were reported.     

Physiology and pathophysiology of iron in hemoglobin-associated diseases

Iron overload and iron toxicity, whether because of increased absorption or iron loading from repeated transfusions, can be major causes of morbidity and mortality in a number of chronic anemias. Significant advances have been made in our understanding of iron homeostasis over the past decade. At the same time, advances in magnetic resonance imaging have allowed clinicians to monitor and quantify iron concentrations noninvasively in specific organs. Furthermore, effective iron chelators are now available, including preparations that can be taken orally. This has resulted in substantial improvement in mortality and morbidity for patients with severe chronic iron overload. This paper reviews the key points of iron homeostasis and attempts to place clinical observations in patients with transfusional iron overload in context with the current understanding of iron homeostasis in humans.     

Q&A: Friends (but sometimes foes) within: the complex evolutionary ecology of symbioses between host and microbes

Over the past decade, there has been a pronounced shift in the study of host–microbe associations, with recognition that many of these associations are beneficial, and often critical, for a diverse array of hosts. There may also be pronounced benefits for the microbes, though this is less well empirically understood. Significant progress has been made in understanding how ecology and evolution shape simple associations between hosts and one or a few microbial species, and this work can serve as a foundation to study the ecology and evolution of host associations with their often complex microbial communities (microbiomes).     

Flagella in prokaryotes and lower eukaryotes.

During the past year, significant advances have been made in the understanding of both prokaryotic and eukaryotic flagella. About 50 genes are dedicated to the assembly and operation of bacterial flagella. Recent discoveries have advanced our understanding of how these genes are regulated and how their products assemble into a functional, rotating organelle. The dynein arms of eukaryotic flagella are now also better understood. Several genes that are found in the mechanochemical macroassemblies have been cloned, and other loci have been identified, suggesting that there is even greater complexity than first expected.     

Phylum Tardigrada: an “individual” approach

Phylum Tardigrada consists of ～1000 tiny, hardy metazoan species distributed throughout terrestrial, limno‐terrestrial and oceanic habitats. Their phylogenetic status has been debated, with current evidence placing them in the Ecdysozoa. Although there have been efforts to explore tardigrade phylogeny using both morphological and molecular data, limitations such as their few morphological characters and low genomic DNA concentrations have resulted in restricted taxonomic coverage. Using a protocol that allows us to identify and extract DNA from individuals, we have sequenced 18S rDNA from 343 tardigrades from across the globe. Using maximum parsimony and Bayesian analyses we have found support for dividing Order Parachela into three super‐families and further evidence that indicates the traditional taxonomic perspective of families in the class Eutardigrada are nonmonophyletic and require re‐working. It appears that conserved morphology within Tardigrada has resulted in conservative taxonomy as we have found cases of several discrete lineages grouped into single genera. Although this work substantially adds to the understanding of the evolution and taxonomy of the phylum, we highlight that inferences gained from this work are likely to be refined with the inclusion of further taxa—specifically representatives of the nine families yet to be sampled. © The Willi Hennig Society 2008.     

Modelling viral and immune system dynamics

During the past 6 years, there have been substantial advances in our understanding of human immunodeficiency virus 1 and other viruses, such as hepatitis B virus and hepatitis C virus, that cause chronic infection. The use of mathematical modelling to interpret experimental results has made a significant contribution to this field. Mathematical modelling is also improving our understanding of T-cell dynamics and the quantitative events that underlie the immune response to pathogens.     

Mechanism of fatty acid synthesis

Significant advances have been made in the past few years in our understanding of the mechanism of synthesis of fatty acids, the structural organization of fatty acid synthetase complexes and the mechanism of regulation of activity of these enzyme systems. Numerous fatty acid synthetase complexes have been purified to homogeneity and the mechanism of synthesis of fatty acids by these enzyme systems has been ascertained from tracer, and recently, kinetic studies. The results obtained by these methods are in complete agreement. Furthermore, the kinetic results have indicated that fatty acid synthesis proceeds by a seven-site ping-pong mechanism. Several of the fatty acid synthetases have been dissociated completely to nonidentical half-molecular weight subunit species and these have been separated by affinity chromatography. From one of these subunits acyl carrier protein has been obtained. Whether the nonidentical subunits can be dissociated into individual proteins or whether these subunits are each comprised of one peptide is still a matter of controversy. However, it appears to us that each of the half-molecular weight subunits is indeed comprised of individual proteins. Studies on the regulation of activity of fatty acid synthetase complexes of avian and mammalian liver have resulted in the separation by affinity chromatography of three species (apo, holo-$\text{a}$ and holo-$\text{b}$) of fatty acid synthetase. Since these species have radically different enzyme activities they may provide a mechanism of short-term regulation of fatty acid synthetase activity. Other studies have shown that the quantity of avian and mammalian liver fatty acid synthetases is controlled by a change in the rate of synthesis of this enzyme complex. This change in the rate of synthesis of enzyme complex is under the control of insulin and glucagon. The former hormone increases the rate of enzyme synthesis, whereas the latter decreases it. Further studies on fatty acid synthetase complexes will undoubtedly concentrate upon more refined aspects of the structural organization of these enzyme systems, including the sequencing of acyl carrier proteins, the effects of protein-protein interaction on the kinetics of the partial reactions of fatty acid synthesis catalyzed by separated enzymes of the complex, the mechanism of hormonal regulation of fatty acid synthetase activity and x-ray diffraction analysis of subunits and complex.     

Siglecs: sialic-acid-binding immunoglobulin-like lectins in cell-cell interactions and signalling

Siglecs are sialic-acid-binding immunoglobulin-like lectins involved in cell-cell interactions and signalling functions in the haemopoietic, immune and nervous systems. Significant advances have been made in our understanding of the link between carbohydrate recognition and signalling for two well-characterised siglecs, CD22 and myelin-associated glycoprotein. Over the past few years, several novel siglecs have been discovered through genomics and functional screens. These "CD33-related" siglecs have molecular features of inhibitory receptors and may be important in regulating leucocyte activation during immune and inflammatory responses.     

Diversity of axonal growth-promoting receptors and regulation of their function.

Growth-promoting receptors for substrate-bound molecules are usually found to belong to the integrin, immunoglobulin, or cadherin families of glycoproteins. New members of each of these families have been identified in the past year, and advances have been made in our understanding of their functional regulation.     

Signaling networks in the plant circadian system

Significant advances have been made during the past year in the genetic and molecular dissection of the plant circadian system. Several proteins involved in circadian clock regulation have been identified and the way that their interactions contribute to temporal organization is starting to emerge. In addition, genomic approaches have identified hundreds of genes under clock control, providing a molecular basis to our understanding of how the clock coordinates plant physiology and development with daily and seasonal environmental cycles.     

Compound‐specific isotope analysis of benthic foraminifer amino acids suggests microhabitat variability in rocky‐shore environments

The abundance and biomass of benthic foraminifera are high in intertidal rocky‐shore habitats. However, the availability of food to support their high biomass has been poorly studied in these habitats compared to those at seafloor covered by sediments. Previous field and laboratory observations have suggested that there is diversity in the food preferences and modes of life among rocky‐shore benthic foraminifera. In this study, we used the stable nitrogen isotopic composition of amino acids to estimate the trophic position, trophic niche, and feeding strategy of individual foraminifera species. We also characterized the configuration and structure of the endobiotic microalgae in foraminifera using transmission electron microscopy, and we identified the origin of endobionts based on nucleotide sequences. Our results demonstrated a large variation in the trophic positions of different foraminifera from the same habitat, a reflection of endobiotic features and the different modes of life and food preferences of the foraminifera. Foraminifera did not rely solely on exogenous food sources. Some species effectively used organic matter derived from endobionts in the cell cytoplasm. The high biomass and species density of benthic foraminifera found in intertidal rocky‐shore habitats are thus probably maintained by the use of multiple nitrogen resources and by microhabitat segregation among species as a consequence.     

PFR2: a curated database of planktonic foraminifera 18S ribosomal DNA as a resource for studies of plankton ecology,biogeography and evolution

Planktonic foraminifera (Rhizaria) are ubiquitous marine pelagic protists producing calcareous shells with conspicuous morphology. They play an important role in the marine carbon cycle, and their exceptional fossil record serves as the basis for biochronostratigraphy and past climate reconstructions. A major worldwide sampling effort over the last two decades has resulted in the establishment of multiple large collections of cryopreserved individual planktonic foraminifera samples. Thousands of 18S rDNA partial sequences have been generated, representing all major known morphological taxa across their worldwide oceanic range. This comprehensive data coverage provides an opportunity to assess patterns of molecular ecology and evolution in a holistic way for an entire group of planktonic protists. We combined all available published and unpublished genetic data to build PFR², the Planktonic foraminifera Ribosomal Reference database. The first version of the database includes 3322 reference 18S rDNA sequences belonging to 32 of the 47 known morphospecies of extant planktonic foraminifera, collected from 460 oceanic stations. All sequences have been rigorously taxonomically curated using a six‐rank annotation system fully resolved to the morphological species level and linked to a series of metadata. The PFR² website, available at http://pfr2.sb-roscoff.fr , allows downloading the entire database or specific sections, as well as the identification of new planktonic foraminiferal sequences. Its novel, fully documented curation process integrates advances in morphological and molecular taxonomy. It allows for an increase in its taxonomic resolution and assures that integrity is maintained by including a complete contingency tracking of annotations and assuring that the annotations remain internally consistent.