Evolution of the genetic machinery of the visual cycle: a novelty of the vertebrate eye?

The discovery in invertebrates of ciliary photoreceptor cells and ciliary (c)-opsins established that at least two of the three elements that characterize the vertebrate photoreceptor system were already present before vertebrate evolution. However, the origin of the third element, a series of biochemical reactions known as the "retinoid cycle," remained uncertain. To understand the evolution of the retinoid cycle, I have searched for the genetic machinery of the cycle in invertebrate genomes, with special emphasis on the cephalochordate amphioxus. Amphioxus is closely related to vertebrates, has a fairly prototypical genome, and possesses ciliary photoreceptor cells and c-opsins. Phylogenetic and structural analyses of the amphioxus sequences related with the vertebrate machinery do not support a function of amphioxus proteins in chromophore regeneration but suggest that the genetic machinery of the retinoid cycle arose in vertebrates due to duplications of ancestral nonvisual genes. These results favor the hypothesis that the retinoid cycle machinery was a functional innovation of the primitive vertebrate eye.     

The earliest history of the deuterostomes: the importance of the Chengjiang Fossil-Lagerst?tte

While the broad framework of deuterostome evolution is now clear, the remarkable diversity of extant forms within this group has rendered the nature of the ancestral types problematic: what, for example, does the common ancestor of a sea urchin and lamprey actually look like? The answer to such questions can be addressed on the basis of remarkably well-preserved fossils from Cambrian Lagerstätten, not least the celebrated Chengjiang Lagerstätte (Yunnan, China). This deposit is particularly important because of its rich diversity of deuterostomes. These include some of the earliest known representatives, among which are the first vertebrates, as well as more enigmatic groups, notably the vetulicolians and yunnanozoans. The latter groups, in particular, have been the subject of some radical divergences in opinion as to their exact phylogenetic placements. Here, we both review the known diversity of Chengjiang deuterostomes and in particular argue that the vetulicolians and yunnanozoans represent very primitive deuterostomes. Moreover, in the latter case we present new data to indicate that the yunnanozoans are unlikely to be any sort of chordate.     

Characterization of auto-regulation of the human cardiac α1 subunit of the L-type calcium channel: Importance of the C-terminus

The carboxyl terminal of the L-type calcium channel _1C subunit comprises approximately one third of the primary structure of the ₁ subunit (> 700 amino acids residues). This region is sensitive to limited posttranslational processing. In heart and brain the _1C subunits are found to be truncated but the C-terminal domain remains functionally present. Based on our previous data we hypothesized that the distal C-terminus (approximately residues 1650–1950) harbors an important, predominantly inhibitory domain. We generated C-terminal-truncated _1C mutants, and after expressing them in combination with a ₃ subunit in HEK-293 cells, electrophysiological experiments were carried out. In order to dissect the important inhibitory part of the C-terminus, trypsin was dialyzed into the cells. The data provide evidence that there are multiple residues within the inhibitory domain that are crucial to the inhibitory process as well as to the enhancement of expressed current by intracellular application of proteases. In addition, the expression of the chimeric mutant _1C1673-DRK₁ demonstrated that the C-terminal is specific for the heart channel.     

Prion hypothesis: the end of the controversy?

Forty-three years have passed since it was first proposed that a protein could be the sole component of the infectious agent responsible for the enigmatic prion diseases. Many discoveries have strongly supported the prion hypothesis, but only recently has this once heretical hypothesis been widely accepted by the scientific community. In the past 3 years, researchers have achieved the 'Holy Grail' demonstration that infectious material can be generated in vitro using completely defined components. These breakthroughs have proven that a misfolded protein is the active component of the infectious agent, and that propagation of the disease and its unique features depend on the self-replication of the infectious folding of the prion protein. In spite of these important discoveries, it remains unclear whether another molecule besides the misfolded prion protein might be an essential element of the infectious agent. Future research promises to reveal many more intriguing features about the rogue prions.     

To the knowledge of the fauna of Microlepidoptera of the “Kurshskaya Kosa” National Park: I

A list of 212 Microlepidoptera species found in the territory of the Curonian Spit (both in its Russian and Lithuanian parts) is given: Micropterigidae (1), Eriocraniidae (1), Nepticulidae (16), Opostegidae (1), Heliozelidae (1), Adelidae (3), Prodoxidae (2), Incurvariidae (2), Tineidae (8), Psychidae (1), Douglasiidae (2), Bucculatricidae (3), Gracillariidae (26), Yponomeutidae (12), Plutellidae (3), Acrolepiidae (2), Glyphipterigidae (3), Lyonetiidae (1), Ethmiidae (1), Depressariidae (12), Elachistidae (20), Chimabachidae (1), Oecophoridae (9), Stathmopodidae (1), Batrachedridae (2), Coleophoridae (25), Momphidae (3), Blastobasidae (2), Cosmopterigidae (3), Choreutidae (1), Schreckensteiniidae (1), Epermeniidae (1), Alucitidae (1), Pterophoridae (7) and Pyralidae (35 species). 113 species of 24 families have been collected in the territory of the “Kurshskaya Kosa” National Park, including 45 species new to the Curonian Spit and 32 species new to Kaliningrad Province.     

The formation of the brush-sticks: modification of chimpanzees or the by-product of folding?

Based on field research and experimental treatments of trees, we investigated the formation of the brush-like shape of digging sticks used by chimpanzees (Pan troglodytes troglodytes). Evidence obtained in the field consisted of digging sticks found in Mboete, Equatorial Guinea, which is a newly reported locality for this type of tool, and Campo, Cameroon. Digging sticks used by chimpanzees in these areas had a brush-like shape at one end, which was quite different from the other end that was probably used for digging. In our tree-breaking experiment, 8 out of 17 species acquired a typical brush-like shape without human modification when broken off, and the shapes of the stumps were similar to those found in the field. Other species did not acquire the brush-like shape naturally or even after human modifications, and the stumps had different shapes from those found in the field. Our findings suggest that the brush-like shapes of digging sticks are often naturally formed when broken off from trees, depending on the nature of the fibre structure, and that the brush-like end is not used as the digging tool. We conclude that the vegetation surrounding termite mounds might influence how chimpanzees combine different types of tools, i.e., digging stick, brush-stick and fishing tool, for obtaining termites.     

Fifty years of cardiac pacing: the dark side of the moon?

Fifty years after its introduction, cardiac pacing has evolved from an experimental medical treatment to an expanding field in today's cardiology. Only recently there is accumulating evidence that prolonged stimulation of the right ventricular apex is associated with clinically significant adverse effects. In this commentary, the potential adverse effects are summarised and potential modifications in contemporary pacing are discussed. (Neth Heart J 2008;16(suppl 1):S12-S14.)     

Beyond the frog: the evolution of homology models of human IKKβ

Nuclear Factor κ B is implicated in tumor progression and chronic inflammatory diseases and is regulated by IκB kinase β (IKKβ). The crystal structure of IKKβ has been recently solved for Xenopus laevis. Homology models of human IKKβ have been developed prior to and after the crystal structure was solved. Here, we compare four models of human IKKβ and evaluate their performance in both broad and focused library docking studies.     

Germline imprinting: battle of the sexes or battle of the X's?

The X chromosome is largely inactivated in spermatogenesis of heterogametic males, and in multiple phyla it encodes few genes specifically expressed in the male germline. Writing in Nature Genetics, Bean et al. report a parallel between male germline X inactivation in nematodes and a fungal gene-silencing mechanism that alters the way we view the evolution of both phenomena.     

Molecular genetics of aging in the fly: Is this the end of the beginning?

How we age and what we can do about it have been uppermost in human thought since antiquity. The many false starts have frustrated experimentalists and theoretical arguments pronouncing the inevitability of the process have created a nihilistic climate among scientists and the public. The identification of single gene alterations that substantially extend life span in nematodes and flies however, have begun to reinvigorate the field. Drosophila's long history of contributions to aging research, rich storehouse of genetic information, and powerful molecular techniques make it an excellent system for studying the molecular mechanisms underlying the process of aging. In recent years, Drosophila has been used to test current theories on aging and explore new directions of potential importance to the biology of aging. One such example is the surprising finding that, as opposed to the commonly held assumption that adult life is a period of random passive decline in which all things are thought to fall apart, the molecular life of the adult fly appears to be a state of dynamic well-regulated change. In the fly, the level of expression of many different genes changes in an invariant, often age-dependent, manner. These as well as other molecular genetic studies and demographic analyses using the fly have begun to challenge widely held ideas about aging providing evidence that aging may be a much more dynamic and malleable process than anticipated. With the enormous success that Drosophila molecular genetics has demonstrated in helping understand complex biological phenomena such as development there is much optimism that similar approaches can be adapted to assist in understanding the process of aging.     

Conversion of the BASE prion strain into the BSE strain: the origin of BSE?

Atypical neuropathological and molecular phenotypes of bovine spongiform encephalopathy (BSE) have recently been identified in different countries. One of these phenotypes, named bovine "amyloidotic" spongiform encephalopathy (BASE), differs from classical BSE for the occurrence of a distinct type of the disease-associated prion protein (PrP), termed PrP(Sc), and the presence of PrP amyloid plaques. Here, we show that the agents responsible for BSE and BASE possess different biological properties upon transmission to transgenic mice expressing bovine PrP and inbred lines of nontransgenic mice. Strikingly, serial passages of the BASE strain to nontransgenic mice induced a neuropathological and molecular disease phenotype indistinguishable from that of BSE-infected mice. The existence of more than one agent associated with prion disease in cattle and the ability of the BASE strain to convert into the BSE strain may have important implications with respect to the origin of BSE and spongiform encephalopathies in other species, including humans.     

Towards a resolution of ‘the paradox of the plankton’: A brief overview of the proposed mechanisms

In plankton ecology, it is a fundamental question as to how a large number of competing phytoplankton species coexist in marine ecosystems under a seemingly-limited variety of resources. This ever-green question was first proposed by Hutchinson [Hutchinson, G.E., 1961. The paradox of the plankton. Am. Nat. 95, 137–145] as ‘the paradox of the plankton’. Starting from Hutchinson [Hutchinson, G.E., 1961. The paradox of the plankton. Am. Nat. 95, 137–145], over more than four decades several investigators have put forward varieties of mechanisms for the extreme diversity of phytoplankton species. In this article, within the boundary of our knowledge, we review the literature of the proposed solutions and give a brief overview of the mechanisms proposed so far. The proposed mechanisms that we discuss mainly include spatial and temporal heterogeneity in physical and biological environment, externally imposed or self-generated spatial segregation, horizontal mesoscale turbulence of ocean characterized by coherent vortices, oscillation and chaos generated by several internal and external causes, stable coexistence and compensatory dynamics under fluctuating temperature in resource competition, and finally the role of toxin-producing phytoplankton in maintaining the coexistence and biodiversity of the overall plankton population that we have proposed recently. We find that, although the different mechanisms proposed so far is potentially applicable to specific ecosystems, a universally accepted theory for explaining plankton diversity in natural waters is still an unachieved goal.     

BRCA1 ubiquitylation of CtIP: Just the tIP of the iceberg?

Ubiquitylation is an important regulatory mechanism of many cellular processes. The breast and ovarian cancer-specific tumour suppressor BRCA1 is well acknowledged to be a RING/E3 ubiquitin ligase, however, identification of its physiological substrates has proved elusive. Recently published data have shown that the BRCA1-interacting protein CtIP is in fact ubiquitylated by BRCA1, and opens new avenues for the isolation of other substrate proteins.     

Amyloid-β: the seeds of darkness

Whilst the amyloid-β (Aβ) hypothesis/centric theory continues to evolve, genetic, biochemical and pathological evidence still suggests that Aβ is central to the etiology of Alzheimer's disease (AD). In particular, Aβ-oligomers/soluble Aβ, may be an earlier determinant of Alzheimer's disease and better correlative of cognitive impairment. Whilst there are a number of Aβ-oligomeric species in existence (making therapeutic and diagnostic biomarker choice cumbersome), their existence is in equilibrium with Aβ-fibrils, the main constituent of cored plaques. Although Alzheimer's disease remains incurable, improvements to Aβ immunotherapies and strategies to target Aβ continue to evolve, with the reliance upon Aβ imaging to shed light on the outcome of therapeutics proving very useful.