Rethinking atoll futures: local resilience to global challenges.

Atoll islands are often perceived as inevitably lost due to rising sea levels. However, unlike other islands, atoll islands are dynamic landforms that have evolved, at least historically, to vertically accrete at a pace commensurate with changing sea levels. Rather than atoll islands' low elevation per se, the impairment of natural accretion processes is jeopardising their persistence.

A Structural Basis for Restricted Codon Recognition Mediated by 2-thiocytidine in tRNA Containing a Wobble Position Inosine.

Three of six arginine codons (CGU, CGC, and CGA) are decoded by two Escherichia coli tRNA isoacceptors. The anticodon stem and loop (ASL) domains of tRNA and tRNA both contain inosine and 2-methyladenosine modifications at positions 34 (I) and 37 (mA). tRNA is also modified from cytidine to 2-thiocytidine at position 32 (sC).

PHOTOSTENT-02: porfimer sodium photodynamic therapy plus stenting versus stenting alone in patients with locally advanced or metastatic biliary tract cancer.

Background: Endobiliary stenting is standard practice for palliation of obstructive jaundice due to biliary tract cancer (BTC). Photodynamic therapy (PDT) may also improve biliary drainage and previous small studies suggested survival benefit.

Aims: To assess the difference in outcome between patients with BTC undergoing palliative stenting plus PDT versus stenting alone.

Structural Studies of Geosmin Synthase, a Bifunctional Sesquiterpene Synthase with αα Domain Architecture That Catalyzes a Unique Cyclization-Fragmentation Reaction Sequence.

Geosmin synthase from Streptomyces coelicolor (ScGS) catalyzes an unusual, metal-dependent terpenoid cyclization and fragmentation reaction sequence. Two distinct active sites are required for catalysis: the N-terminal domain catalyzes the ionization and cyclization of farnesyl diphosphate to form germacradienol and inorganic pyrophosphate (PPi), and the C-terminal domain catalyzes the protonation, cyclization, and fragmentation of germacradienol to form geosmin and acetone through a retro-Prins reaction. A unique αα domain architecture is predicted for ScGS based on amino acid sequence: each domain contains the metal-binding motifs typical of a class I terpenoid cyclase, and each domain requires Mg(2+) for catalysis.

Structural analysis of base substitutions in Thermus thermophilus 16S rRNA conferring streptomycin resistance.

Streptomycin is a bactericidal antibiotic that induces translational errors. It binds to the 30S ribosomal subunit, interacting with ribosomal protein S12 and with 16S rRNA through contacts with the phosphodiester backbone. To explore the structural basis for streptomycin resistance, we determined the X-ray crystal structures of 30S ribosomal subunits from six streptomycin-resistant mutants of Thermus thermophilus both in the apo form and in complex with streptomycin.

The central role of protein S12 in organizing the structure of the decoding site of the ribosome.

The ribosome decodes mRNA by monitoring the geometry of codon-anticodon base-pairing using a set of universally conserved 16S rRNA nucleotides within the conformationally dynamic decoding site. By applying single-molecule FRET and X-ray crystallography, we have determined that conditional-lethal, streptomycin-dependence mutations in ribosomal protein S12 interfere with tRNA selection by allowing conformational distortions of the decoding site that impair GTPase activation of EF-Tu during the tRNA selection process. Distortions in the decoding site are reversed by streptomycin or by a second-site suppressor mutation in 16S rRNA.

Expanded use of sense codons is regulated by modified cytidines in tRNA.

Codon use among the three domains of life is not confined to the universal genetic code. With only 22 tRNA genes in mammalian mitochondria, exceptions from the universal code are necessary for proper translation. A particularly interesting deviation is the decoding of the isoleucine AUA codon as methionine by the one mitochondrial-encoded tRNA(Met).

A structural basis for streptomycin-induced misreading of the genetic code.

During protein synthesis, the ribosome selects aminoacyl-transfer RNAs with anticodons matching the messenger RNA codon present in the A site of the small ribosomal subunit. The aminoglycoside antibiotic streptomycin disrupts decoding by binding close to the site of codon recognition. Here we use X-ray crystallography to define the impact of streptomycin on the decoding site of the Thermus thermophilus 30S ribosomal subunit in complexes with cognate or near-cognate anticodon stem-loop analogues and messenger RNA.

Adapting federated cyberinfrastructure for shared data collection facilities in structural biology.

Early stage experimental data in structural biology is generally unmaintained and inaccessible to the public. It is increasingly believed that this data, which forms the basis for each macromolecular structure discovered by this field, must be archived and, in due course, published. Furthermore, the widespread use of shared scientific facilities such as synchrotron beamlines complicates the issue of data storage, access and movement, as does the increase of remote users.

Differential function of lip residues in the mechanism and biology of an anthrax hemophore.

To replicate in mammalian hosts, bacterial pathogens must acquire iron. The majority of iron is coordinated to the protoporphyrin ring of heme, which is further bound to hemoglobin. Pathogenic bacteria utilize secreted hemophores to acquire heme from heme sources such as hemoglobin.

Human tRNA(Lys3)(UUU) is pre-structured by natural modifications for cognate and wobble codon binding through keto-enol tautomerism.

Human tRNA(Lys3)(UUU) (htRNA(Lys3)(UUU)) decodes the lysine codons AAA and AAG during translation and also plays a crucial role as the primer for HIV-1 (human immunodeficiency virus type 1) reverse transcription. The posttranscriptional modifications 5-methoxycarbonylmethyl-2-thiouridine (mcm(5)s(2)U(34)), 2-methylthio-N(6)-threonylcarbamoyladenosine (ms(2)t(6)A(37)), and pseudouridine (Ψ(39)) in the tRNA's anticodon domain are critical for ribosomal binding and HIV-1 reverse transcription. To understand the importance of modified nucleoside contributions, we determined the structure and function of this tRNA's anticodon stem and loop (ASL) domain with these modifications at positions 34, 37, and 39, respectively (hASL(Lys3)(UUU)-mcm(5)s(2)U(34);ms(2)t(6)A(37);Ψ(39)).

Modification of 16S ribosomal RNA by the KsgA methyltransferase restructures the 30S subunit to optimize ribosome function.

All organisms incorporate post-transcriptional modifications into ribosomal RNA, influencing ribosome assembly and function in ways that are poorly understood. The most highly conserved modification is the dimethylation of two adenosines near the 3' end of the small subunit rRNA. Lack of these methylations due to deficiency in the KsgA methyltransferase stimulates translational errors during both the initiation and elongation phases of protein synthesis and confers resistance to the antibiotic kasugamycin.

The crystal structure of the ribosome bound to EF-Tu and aminoacyl-tRNA.

The ribosome selects a correct transfer RNA (tRNA) for each amino acid added to the polypeptide chain, as directed by messenger RNA. Aminoacyl-tRNA is delivered to the ribosome by elongation factor Tu (EF-Tu), which hydrolyzes guanosine triphosphate (GTP) and releases tRNA in response to codon recognition. The signaling pathway that leads to GTP hydrolysis upon codon recognition is critical to accurate decoding.

Active matrix metalloproteinase-2 promotes apoptosis of hepatic stellate cells via the cleavage of cellular N-cadherin.

Background And Aims: Hepatic stellate cells (HSC) are known to synthesise excess matrix that characterises liver fibrosis and cirrhosis. Activated HSC express the matrix-degrading matrix metalloproteinase enzymes (MMPs) and their tissue inhibitors (TIMPs). During spontaneous recovery from experimental liver fibrosis, the expression of TIMP-1 declines and hepatic collagenolytic activity increases.

GTPase activation of elongation factor EF-Tu by the ribosome during decoding.

We have used single-particle reconstruction in cryo-electron microscopy to determine a structure of the Thermus thermophilus ribosome in which the ternary complex of elongation factor Tu (EF-Tu), tRNA and guanine nucleotide has been trapped on the ribosome using the antibiotic kirromycin. This represents the state in the decoding process just after codon recognition by tRNA and the resulting GTP hydrolysis by EF-Tu, but before the release of EF-Tu from the ribosome. Progress in sample purification and image processing made it possible to reach a resolution of 6.

Mechanism for expanding the decoding capacity of transfer RNAs by modification of uridines.

One of the most prevalent base modifications involved in decoding is uridine 5-oxyacetic acid at the wobble position of tRNA. It has been known for several decades that this modification enables a single tRNA to decode all four codons in a degenerate codon box. We have determined structures of an anticodon stem-loop of tRNA(Val) containing the modified uridine with all four valine codons in the decoding site of the 30S ribosomal subunit.

Miliarial gout (a new entity).

Background: Tophaceous gout typically presents as a subcutaneous, nodular collection of monosodium urate crystals sharply circumscribed from surrounding tissues. Although intradermal cutaneous manifestations of gout have been described, no reported cases of miliarial gout remain.

Objective: We describe the first known presentation of miliarial gout and list other uncommon cutaneous manifestations of gouty tophi.

Cutaneous reaction to drugs used for erectile dysfunction: case report and review of the literature.

Background: In the past 9 years, drugs for erectile dysfunction (ED) have been increasingly prescribed for men with erectile difficulty. These drugs, phosphodiesterase 5 (PDE5) inhibitors, help men with ED obtain and sustain an erection, improving both sexual function and sexual performance satisfaction. However, these drugs contain side effects.

Structure of the 70S ribosome complexed with mRNA and tRNA.

The crystal structure of the bacterial 70S ribosome refined to 2.8 angstrom resolution reveals atomic details of its interactions with messenger RNA (mRNA) and transfer RNA (tRNA). A metal ion stabilizes a kink in the mRNA that demarcates the boundary between A and P sites, which is potentially important to prevent slippage of mRNA.

Crystal structures of the ribosome in complex with release factors RF1 and RF2 bound to a cognate stop codon.

During protein synthesis, translational release factors catalyze the release of the polypeptide chain when a stop codon on the mRNA reaches the A site of the ribosome. The detailed mechanism of this process is currently unknown. We present here the crystal structures of the ribosome from Thermus thermophilus with RF1 and RF2 bound to their cognate stop codons, at resolutions of 5.

The comparison and validity of troponin I assay systems in diagnosing myocardial ischemic injury after surgical coronary revascularization.

Objective: A prospective observational study was conducted to test the agreement between 2 commercially available automated cardiac troponin-I immunoassay systems (Opus Plus, Behring Diagnostics UK Ltd, Hounslow, UK; AxSYM, Abbott Laboratories, Abbott Park, IL) and to determine a normal reference range and threshold value indicative of perioperative myocardial infarction (PMI) after elective coronary artery bypass graft (CABG) surgery for the Opus Plus system.

Design: Prospective, observational study. Setting : Single institution, cardiothoracic specialty hospital.

Comparison of the efficacy and safety of the 308 nm excimer laser for the treatment of localized psoriasis in adults and in children: a pilot study.

The 308-nm excimer laser has been shown to be safe and efficacious in the treatment of localized mild-to-moderate plaque-type psoriasis in adults. However, the laser's safety and efficacy has not yet been demonstrated in children. Four of seven children with a mean age of 11.

Bidirectional imaging and modeling of skin texture.

In this paper, we present a method of skin imaging called bidirectional imaging that captures significantly more properties of appearance than standard imaging. The observed structure of the skin's surface is greatly dependent on the angle of incident illumination and the angle of observation. Specific protocols to achieve bidirectional imaging are presented and used to create the Rutgers Skin Texture Database (clinical component).