Lymphatic vasculature development

Although the process of blood vasculature formation has been well documented, little is known about lymphatic vasculature development, despite its importance in normal and pathological conditions. The lack of specific lymphatic markers has hampered progress in this field. However, the recent identification of genes that participate in the formation of the lymphatic vasculature denotes the beginning of a new era in which better diagnoses and therapeutic treatment(s) of lymphatic disorders could become a reachable goal.     

Lymphatic vasculature in ovarian cancer

Ovarian cancer (OVCA) is the second most common gynecological cancer and one of the leading causes of cancer related mortality among women. Recent studies suggest that among ovarian cancer patients at least 70% of the cases experience the involvement of lymph nodes and metastases through lymphatic vascular network. However, the impact of lymphatic system in the growth, spread and the evolution of ovarian cancer, its contribution towards the landscape of ovarian tissue resident immune cells and their metabolic responses is still a major knowledge gap. In this review first we present the epidemiological aspect of the OVCA, the lymphatic architecture of the ovary, we discuss the role of lymphatic circulation in regulation of ovarian tumor microenvironment, metabolic basis of the upregulation of lymphangiogenesis which is often observed during progression of ovarian metastasis and ascites development. Further we describe the implication of several mediators which influence both lymphatic vasculature as well as ovarian tumor microenvironment and conclude with several therapeutic strategies for targeting lymphatic vasculature in ovarian cancer progression in present day.     

Defining a monophyletic Cardinalini: a molecular perspective

Within the New World nine-primaried oscine assemblage, feeding morphology and behavior have long been used as a guideline for assigning membership to subgroups. For example, birds with stout, conical bills capable of crushing heavy seeds have generally been placed within the tribe Cardinalini (cardinal-grosbeaks). Many workers have tried to characterize this group more definitively, using a variety of morphological characters; however, the characters used often conflicted with one another. Previous molecular studies addressing the monophyly of Cardinalini have had only limited sampling within the group. In this study, we analyze mtDNA sequence data from all genera and 34 of the 42 Cardinalini species (sensu [Sibley, C.G., Monroe, B.L., 1990. Distribution and Taxonomy of the Birds of the World, Yale University Press, New Haven, CT]) to address the monophyly of the group and to reconstruct the most complete phylogeny of this tribe published to date. We found strong support for a redefined Cardinalini that now includes some members previously placed within Thraupini (tanagers; the genera Piranga, Habia, Chlorothraupis, and Amaurospiza) and some members previously placed within the Parulini (wood-warblers; the genus Granatellus). In addition, some genera traditionally considered members of the Cardinalini are shown to have affinities with other groups (the genera Porphyrospiza, Parkerthraustes, and Saltator). Our redefined Cardinalini contains 48 species, six more than are listed in Sibley and Monroe's (1990) taxonomy of the group. Within the nine-primaried oscine assemblage, the Cardinalini are more closely related to the Thraupini (tanagers) than they are to the Emberizini (sparrows), Parulini (wood-warblers), or Icterini (blackbirds), consistently forming a monophyletic group with Thraupini across all analyses. The reconfigured Cardinalini is comprised of five well-supported, major clades: (1) a "masked" clade (Piranga, Cardinalis, Caryothraustes, Periporphyrus, and Rhodothraupis), (2) a "blue" clade (Amaurospiza, Cyanocompsa, Cyanoloxia, Passerina, and Spiza), (3) a clade containing the genera Habia and Chlorothraupis, (4) a clade containing all species of Granatellus, and (5) a clade containing only species of Pheucticus. Diversification of these five lineages from one another occurred relatively rapidly during the mid-Pliocene, around 5 or 8 million years ago. Each of these major clades includes both North and South American species; thus, a complex biogeographic history is inferred for the group.     

Plant self-incompatibility systems: a molecular evolutionary perspective

Incompatibility recognition systems preventing self-fertilization have evolved several times in independent lineages of Angiosperm plants, and three main model systems are well characterized at the molecular level [the gametophytic self-incompatibility (SI) systems of Solanaceae, Rosaceae and Anthirrhinum, the very different system of poppy, and the system in Brassicaceae with sporophytic control of pollen SI reactions]. In two of these systems, the genes encoding both components of pollen-pistil recognition are now known, showing clearly that these two proteins are distinct, that is, SI is a lock-and-key mechanism. Here, we review recent findings in the three well-studied systems in the light of these results and analyse their implications for understanding polymorphism and coevolution of the two SI genes, in the context of a tightly linked genome region.     

Lymphatic endothelium: morphological, molecular and functional properties

The lymphatic microvasculature is uniquely adapted for the continuous removal of interstitial fluid and proteins, and is an important point of entry for leukocytes and tumor cells. The traditional view that lymphatic capillaries are passive participants in these tasks is currently being challenged. This overview highlights recent advances in our understanding of the molecular mechanisms underlying the formation and function of lymphatic vessels.     

Genetics of asthma: a molecular biologist perspective

Viruses are the predominant infectious cause of asthma exacerbations in the developed world. In addition, recent evidence strongly suggests that viral infections may also have a causal role in the development of childhood asthma. In this article, we will briefly describe the general perception of how the link between infections and asthma has changed over the last century, and then focus on very recent developments that have provided new insights into the contribution of viruses to asthma pathogenesis. Highlighted areas include the contribution of severe early life viral infections to asthma inception, genetic determinants of severe viral infections in infancy, the differences in innate and adaptive immune system cytokine responses to viral infection between asthmatic and nonasthmatic subjects, and a potential vaccine strategy to prevent severe early life virally-induced illness.     

Astrocyte dysfunction in neurological disorders: a molecular perspective

Recent work on glial cell physiology has revealed that glial cells, and astrocytes in particular, are much more actively involved in brain information processing than previously thought. This finding has stimulated the view that the active brain should no longer be regarded solely as a network of neuronal contacts, but instead as a circuit of integrated, interactive neurons and glial cells. Consequently, glial cells could also have as yet unexpected roles in the diseased brain. An improved understanding of astrocyte biology and heterogeneity and the involvement of these cells in pathogenesis offers the potential for developing novel strategies to treat neurological disorders.     

RNA solvation: a molecular dynamics simulation perspective.

With the availability of accurate methods to treat the electrostatic long-range interactions, molecular dynamics simulations have resulted in refined dynamical models of the structure of the hydration shell around RNA motifs. The models reviewed here range from basic Watson-Crick to more specific noncanonical base pairs, from "simple" double helices to RNA molecules displaying more complex tertiary folds, and from DNA/RNA hybrid double helices to RNA hybrids formed with a chemically modified strand.     

Number of ancestral human species: a molecular perspective

Despite the remarkable developments in molecular biology over the past three decades, anthropological genetics has had only limited impact on systematics in human evolution. Genetics offers the opportunity to objectively test taxonomies based on morphology and may be used to supplement conventional approaches to hominid systematics. Our analyses, examining chromosomes and 46 estimates of genetic distance, indicate there may have been only around 4 species on the direct line to modern humans and 5 species in total. This contrasts with current taxonomies recognising up to 23 species.

The genetic proximity of humans and chimpanzees has been used to suggest these species are congeneric. Our analysis of genetic distances between them is consistent with this proposal. It is time that chimpanzees, living humans and all fossil humans be classified in Homo. The creation of new genera can no longer be a solution to the complexities of fossil morphologies. Published genetic distances between common chimpanzees and bonobos, along with evidence for interbreeding, suggest they should be assigned to a single species.

The short distance between humans and chimpanzees also places a strict limit on the number of possible evolutionary side branches that might be recognised on the human lineage. All fossil taxa were genetically very close to each other and likely to have been below congeneric genetic distances seen for many mammals.

Our estimates of genetic divergence suggest that periods of around 2 million years are required to produce sufficient genetic distance to represent speciation. Therefore, Neanderthals and so-called H. erectus were genetically so close to contemporary H. sapiens they were unlikely to have been separate species. Thus, it is likely there was only one species of human (H. sapiens) for most of the last 2 million years. We estimate the divergence time of H. sapiensfrom 16 genetic distances to be around 1.7 Ma which is consistent with evidence for the earliest migration out of Africa. These findings call into question the mitochondrial «African Eve» hypothesis based on a far more recent origin for H. sapiens and show that humans did not go through a bottleneck in their recent evolutionary history.

Given the large offset in evolutionary rates of molecules and morphology seen in human evolution, Homo species are likely to be characterised by high levels of morphological variation and low levels of genetic variability. Thus, molecular data suggest the limits for intraspecific morphological variation used by many palaeoanthropologists have been set too low. The role of phenotypic plasticity has been greatly underestimated in human evolution.

We call into question the use of mtDNA for studies of human evolution. This DNA is under strong selection, which violates the assumption of selective neutrality. This issue should be addressed by geneticists, including a reassessment of its use for molecular clocks. There is a need for greater cooperation between palaeoanthropologists and anthropological geneticists to better understand human evolution and to bring palaeoanthropology into the mainstream of evolutionary biology.     

The evolution of self-incompatibility: a molecular voyeur's perspective

This review summarises current understanding of the evolution of self-incompatibility inferred from DNA sequence analysis. Self-incompatibility in many plant families is controlled by a single, highly polymorphicS-locus which, in the Solanaceae, encodes an allelic series of stylar ribonucleases known as the S-RNases. PCR approaches are a convenient way to examine the diversity of S-RNase sequences within and between wild populations of a self-incompatible species and provide a unique view into the species' current and historic population structure. Similar molecular appoaches have also been used to show that S-RNases are involved in self-incompatibility in families other than the Solanaceae. A model for the evolution of ribonuclease-based self-incompatibility systems is discussed.     

The Spitzenkörper: a molecular perspective

The Spitzenkörper is a dynamic structure present at the tips of hyphal cells with a single highly polarized growth site. It is closely connected with cell morphogenesis and polar growth, and is only present at actively growing sites. Morphogenesis of such highly polarized cells is complex, and requires the coordinated action of multiple protein complexes. We discuss the relevance of these complexes for the structure and function of the Spitzenkörper.     

Canalization: A molecular genetic perspective

The phenomenon of ‘canalization’ - the genetic capacity to buffer developmental pathways against mutational or environmental perturbations - was first characterized in the late 1930s and early 1940s. Despite enormous subsequent progress in understanding the nature of the genetic material and the molecular basis of gene expression, there have been few attempts to interpret the classical work on canalization in molecular genetic terms. Some recent findings, however, bear on one form of canalization, ‘genetic canalization’, the stabilization of development against mutational effects. These data indicate that co-expressed paralogous genes can function as mutual ‘back-up’ elements in developmental processes. Paralogues, however, are far from the only basis of canalization: other genetic sources can be readily envisaged and some of these are described here. The evolutionary questions about genetic canalization and the mechanistic questions about developmental instability that still need to be addressed are also briefly discussed.     

Leech segmentation: A molecular perspective

A variety of leech homeobox genes have been identified by homology with genes that are known to bring about the regionalization and segmentation of the anteroposterior body axis in other organisms. Embryonic expression patterns suggest a number of interphyletic similarities in the way that these genes are utilized. However, several interesting differences have also been observed. In particular, transplantation experiments in the leech embryo have shown that axially aligned patterns of homeobox gene expression are not specified by a global pattern of positional cues. Rather, the leech independently establishes anteroposterior patterns of gene expression in each of five discrete stem cell lineages, and these patterns are brought into their final alignment through a process of morphogenetic assembly.     

Evolution and biodiversity of Antarctic organisms: a molecular perspective

The Antarctic biota is highly endemic, and the diversity and abundance of taxonomic groups differ from elsewhere in the world. Such characteristics have resulted from evolution in isolation in an increasingly extreme environment over the last 100 Myr. Studies on Antarctic species represent some of the best examples of natural selection at the molecular, structural and physiological levels. Analyses of molecular genetics data are consistent with the diversity and distribution of marine and terrestrial taxa having been strongly influenced by geological and climatic cooling events over the last 70 Myr. Such events have resulted in vicariance driven by continental drift and thermal isolation of the Antarctic, and in pulses of species range contraction into refugia and subsequent expansion and secondary contact of genetically distinct populations or sister species during cycles of glaciation. Limited habitat availability has played a major role in structuring populations of species both in the past and in the present day. For these reasons, despite the apparent simplicity or homogeneity of Antarctic terrestrial and marine environments, populations of species are often geographically structured into genetically distinct lineages. In some cases, genetic studies have revealed that species defined by morphological characters are complexes of cryptic or sibling species. Climate change will cause changes in the distribution of many Antarctic and sub-Antarctic species through affecting population-level processes such as life history and dispersal.     

The tachykinin tale: molecular recognition in a historical perspective

Crystallography, mutational mapping and crosslinking are but a few of the experimental techniques that have helped to elucidate the underlying principles of molecular recognition between macromolecules and to improve our understanding of the evolution of the structure-activity relationship (SAR). While this development has been particularly successful for small and rigid ligands and substrates that bind to larger hydrophilic biomolecules, our understanding of membrane-embedded proteins is still rather limited. This review uses the example of the neuropeptide family of tachykinins and their G-protein coupled receptors (GPCR) to present how complementary experimental strategies over the past decades have nourished and modified conceptual models of the structural requisites of molecular recognition and function. Given the little we know, the pertinent question is how we proceed from here.     

Diversity and geographic distribution of benthic foraminifera: a molecular perspective

The diversity and distribution of modern benthic foraminifera has been extensively studied in order to aid the paleoecological interpretation of their fossil record. Traditionally, foraminiferal species are identified based on morphological characters of their organic, agglutinated or calcareous tests. Recently, however, new molecular techniques based on analysis of DNA sequences have been introduced to study the genetic variation in foraminifera. Although the number of species for which DNA sequence data exist is still very limited, it appears that morphology-based studies largely underestimated foraminiferal diversity. Here, we present two examples of the use of DNA sequences to examine the diversity of benthic foraminifera. The first case deals with molecular and morphological variations in the well-known and common calcareous genus Ammonia. The second case presents molecular diversity in the poorly documented group of monothalamous (single-chambered) foraminifera. Both examples perfectly illustrate high cryptic diversity revealed in almost all molecular studies. Molecular results also confirm that the majority of foraminiferal species have a restricted geographic distribution and that globally distributed species are rare. This is in opposition to the theory that biogeography has no impact on the diversity of small-sized eukaryotes. At least in the case of foraminifera, size does not seem to have a main impact on dispersal capacities. However, the factors responsible for the dispersal of foraminiferal species and the extension of their geographic ranges remain largely unknown. Special Issue: Protist diversity and geographic distribution. Guest editor: W. Foissner.     

Fear memory and the amygdala: insights from a molecular perspective

The amygdala modulates memory consolidation and the storage of emotionally relevant information in other brain areas, and itself comprises a site of neural plasticity during aversive learning. These processes have been intensively studied in Pavlovian fear conditioning, a leading aversive learning paradigm that is dependent on the structural and functional integrity of the amygdala. The rapidness and persistence, and the relative ease, with which this conditioning paradigm can be applied to a great variety of species have made it an attractive model for neurochemical and electrophysiological investigations on memory formation. In this review we summarise recent studies which have begun to unravel cellular processes in the amygdala that are critical for the formation of long-term fear memory and have identified molecular factors and mechanisms of neural plasticity in this brain area.