The vertebrate segmentation clock: the tip of the iceberg

The vertebrate segmentation clock was identified 10 years ago as a molecular oscillator associated with the rhythmic production of embryonic somites. Since then, three major signaling pathways--Notch, FGF, and Wnt--have been shown to be activated periodically during segmentation and proposed to constitute the clockwork of the system. However, recent results from zebrafish embryonic studies demonstrate that Notch signaling is involved in the coupling of oscillations among cells rather than in the pacemaker of the oscillator. Furthermore, genetic analyses in mouse indicate that Wnt and FGF play only a permissive role in the control of the oscillations. Therefore, the nature of the segmentation clock pacemaker still remains elusive.     

Conjugative transposons: the tip of the iceberg

Elements that excise and integrate, such as prophages, and transfer by conjugation, such as plasmids, have been found in various bacteria. These elements appear to have a diversified set of characteristics including cell-to-cell contact using pili or cell aggregation, transfer of single-stranded or double-stranded DNA, low or high specificity of integration and serine or tyrosine recombinases. This has led to a highly heterogeneous nomenclature, including conjugative transposons, integrative 'plasmids', genomic islands and numerous unclassified elements. However, all these elements excise by site-specific recombination, transfer the resulting circular form by conjugation and integrate by recombination between a specific site of this circular form and a site in the genome of their host. Whereas replication of the circular form probably occurs during conjugation, this replication is not involved in the maintenance of the element. In this review, we show that these elements share very similar characteristics and, therefore, we propose to classify them as integrative and conjugative elements (ICEs). These elements evolve by acquisition or exchanges of modules with various transferable elements including at least ICEs and plasmids. The ICEs are probably widespread among the bacteria.     

Pathogenicity islands: the tip of the iceberg.

Pathogenicity islands represent distinct genetic elements encoding virulence factors of pathogenic bacteria. Pathogenicity islands belong to the class of genomic islands, which are common genetic elements sharing a set of unifying features. Genomic islands have been acquired by horizontal gene transfer. In recent years many different genomic islands have been discovered in a variety of pathogenic as well as non-pathogenic bacteria. Because they promote genetic variability, genomic islands play an important role in microbial evolution.     

Copy-number polymorphisms: mining the tip of an iceberg

Copy-number polymorphisms (CNPs) represent a greatly underestimated aspect of human genetic variation. Recently, two landmark studies reported genome-wide analyses of CNPs in normal individuals and represent the beginning of an understanding of this type of large-scale variation. Future array-CGH-based CNP analyses should include standard criteria on a common microarray platform. It is only when parallel analyses of CNPs and SNPs are performed in an integrated format that we will obtain a global picture of our genetic diversity.     

Magnesium transport and function in plants: the tip of the iceberg

The maintenance of Mg²⁺ homeostasis in the plant is essential for viability. This review describes Mg²⁺ functions and balancing in plants, with special focus on the existing knowledge of the involved transport mechanisms. Mg²⁺ is essential for the function of many cellular enzymes and for the aggregation of ribosomes. Mg²⁺ concentrations also modulate ionic currents across the chloroplast and the vacuolar membranes, and might thus regulate ion balance in the cell and stomatal opening. The significance of Mg²⁺ homeostasis has been particularly established with regard to Mg²⁺'s role in photosynthesis. Mg²⁺ is the central atom of the chlorophyll molecule, and fluctuations in its levels in the chloroplast regulate the activity of key photosynthetic enzymes. Relatively little is known of the proteins mediating Mg²⁺ uptake and transport in plants. The plant vacuole seem to play a key role in Mg²⁺ homeostasis in plant cells. Physiological and molecular evidence indicate that Mg²⁺ entry to the vacuole is mediated by Mg²⁺/H⁺ exchangers. The Arabidopsis vacuolar Mg²⁺/H⁺ exchanger, AtMHX, is highly transcribed at the vascular tissue, apparently most abundantly at the xylem parenchyma. Inclusion of Mg²⁺ ions into the vacuoles of this tissue may determine their partitioning between the various plant organs. Impacts of Mg²⁺ imbalance are described with respect for both plant physiology and for its nutritional value to animal and human.     

Navigating the tip of the genomic iceberg: Next-generation sequencing for plant systematics

? Premise of the study: Just as Sanger sequencing did more than 20 years ago, next-generation sequencing (NGS) is poised to revolutionize plant systematics. By combining multiplexing approaches with NGS throughput, systematists may no longer need to choose between more taxa or more characters. Here we describe a genome skimming (shallow sequencing) approach for plant systematics. ? Methods: Through simulations, we evaluated optimal sequencing depth and performance of single-end and paired-end short read sequences for assembly of nuclear ribosomal DNA (rDNA) and plastomes and addressed the effect of divergence on reference-guided plastome assembly. We also used simulations to identify potential phylogenetic markers from low-copy nuclear loci at different sequencing depths. We demonstrated the utility of genome skimming through phylogenetic analysis of the Sonoran Desert clade (SDC) of Asclepias (Apocynaceae). ? Key results: Paired-end reads performed better than single-end reads. Minimum sequencing depths for high quality rDNA and plastome assemblies were 40× and 30×, respectively. Divergence from the reference significantly affected plastome assembly, but relatively similar references are available for most seed plants. Deeper rDNA sequencing is necessary to characterize intragenomic polymorphism. The low-copy fraction of the nuclear genome was readily surveyed, even at low sequencing depths. Nearly 160000 bp of sequence from three organelles provided evidence of phylogenetic incongruence in the SDC. ? Conclusions: Adoption of NGS will facilitate progress in plant systematics, as whole plastome and rDNA cistrons, partial mitochondrial genomes, and low-copy nuclear markers can now be efficiently obtained for molecular phylogenetics studies.     

Lipid transfer and signaling at organelle contact sites: the tip of the iceberg

Membrane contact sites (MCSs) are formed by the close apposition of membranes of two organelles. They are zones where signals and small molecules, such as lipids and calcium, are exchanged between intracellular compartments. The past few years have seen considerable progress in our understanding of how MCSs form and facilitate the exchange of lipids and signals. Here we summarize what has been learned about MCSs between the endoplamic reticulum (ER) and the plasma membrane, the ER and mitochondria, and the ER and endosomes or lysosomes. These findings suggest that we are just beginning to understand how MCSs form and function.     

The tip of the iceberg: quinolone-resistance conferred by mutations in gyrA gene in non-typhoidal Salmonella strains

Food-borne infections due to Salmonella spp. seldom require antimicrobial therapy, but this is compulsory in systemic salmonellosis. Salmonella resistance to a large panel of antibiotics has been described worldwide. Since the introduction of nalidixic acid in therapy, Salmonella spp. have steadily developed resistance, especially over the last three decades. The source of quinolone resistance is thought to be the selective pressure determined by the use of quinolones in both human and veterinary practices. Resistance acquisition of Salmonella strains is a stepwise process. Several mechanisms are described, which can lead to the development of quinolone resistance. The main mechanism is considered to be linked with mutations in the quinolone-resistance determining region (QRDR) of the target genes (gyrA and gyrB encoding DNA gyrase, and parC and parE encoding topoisomerase IV). This first step in mutational resistance usually determines a rise in the nalidixic acid minimal inhibitory concentration (MIC). The most common amino acid substitutions in the GyrA subunit, resulting in varied degrees of quinolone resistance, occur at codons Ser83 and Asp87. Higher levels of resistance may occur by further mutational steps, with amino acid changes in the same or a different target enzyme. Other mechanisms are as well involved, like increased efflux or plasmid-mediated resistance. Acknowledgement of the epidemiology and the onset mechanisms of quinolone resistance in Salmonella spp. is compulsory, and surveillance for resistant bacteria among human, animal and food sources remains critical.     

The making of "The Genoma Music."

Both genetic and musical sequences are ordered structures composed of combinations of a small number of elements, of nucleotides and musical notes. In the case of the genome, the emergence of cellular functions makes the order meaningful; in the case of musical sequences, the consequence of order is the production of mysterious esthetical effects in the human mind. Can any musical significance be found in DNA sequence? In this work, we present the technique used to convert DNA sequences into musical sequences. The musical equivalent of the sequence of a number of genes, either of fungal origin, such as Candida albicans or Sacharomyces cerevisiae (SLT2), or belonging to the human genome (genes involved in Alzheimer syndrome, blindness, and deafness such as Connexine 26 gene) has been obtained. Non-coding sequences are also important in life and music. The non-coding alphoid sequence has also been translated into a musical sequence, in this case using Fibonacci golden number basic series as structural helper. The elementary musical sequence derived from DNA sequence has served as an imposing frame in which rhythms, sounds, and melodies have been harmonically inserted. The Genoma Music Project is essentially a creative metaphor of the basic unity between the human mind and the natural ordered structure of life.     

Insulin-induced hypoglycaemia in an accident and emergency department: the tip of an iceberg?

In one year a prospective survey in a large accident and emergency department identified 204 admissions of adults with severe hypoglycaemia, 200 in insulin-treated patients. Ninety-six had one admission while 34 others were admitted on 104 occasions. Of the 130 patients, 111 attended diabetic clinics in Nottingham, forming 9% of a known clinic population of 1229 on insulin treatment. Since many other episodes of hypoglycaemia were presumably treated outside hospital, 9% a year is a minimum estimate of the incidence of severe hypoglycaemia in our area. The mean insulin dose was 1.2 units/kilogram/day for those admitted twice or more and 0.9 U/kg/day for those admitted once; these doses were significantly higher than those of an age-matched clinic population. A year after the latest admission with hypoglycaemia, the mean insulin dose in the group with two or more admissions had fallen to 0.8 U/kg/day, suggesting that over-treatment had been an important causal factor. A similarly high incidence has been reported in other studies, and we believe that it is due mainly to the inadequacy of conventional subcutaneous insulin treatment.     

Alternative splicing and proteome diversity in plants: the tip of the iceberg has just emerged

Alternative splicing has recently emerged as one of the most significant generators of functional complexity in several relatively well-studied animal genomes, but little is known about the extent of this phenomenon in higher plants. However, recent computational and experimental studies discussed here suggest that alternative splicing probably plays a far more significant role in the generation of proteome diversity in plants than was previously thought.