bluuebunny/crossref_metadata_2025_split huggingface dataset:
Haematopoietic stem cell transplantation: can our genes predict clinical outcome?
Authors: Dickinson Anne M. , Harrold Jane L. , Cullup Hannah 
Published: November 2007

AbstractHaematopoietic stem cell transplantation (HSCT) is currently the only curative treatment for many patients with malignant and non-malignant haematological diseases. The success of HSCT is greatly reduced by the development of complications, which include graft-versus-host disease (GVHD), relapse and infection. Human leukocyte antigen (HLA) matching of patients and donors is essential, but does not completely prevent these complications; non-HLA genes may also have an impact upon transplant outcome. Polymorphisms within genes that are associated with an individual's capability to mount an immune response to alloantigen and infectious pathogens and/or response to drugs (pharmacogenomics) are all currently being studied for their association with HSCT outcome. This review summarises the potential role of non-HLA polymorphisms in predicting HSCT outcome, from studies on retrospective transplant cohorts of HLA-identical siblings and matched unrelated donors. The clinical relevance and interpretation of non-HLA genetics, and how these could be used alongside clinical risk factors in HSCT, are also discussed.
Cerebellar Bergmann glia: an important model to study neuron–glia interactions
Authors: López-Bayghen Esther , Rosas Sandra , Castelán Francisco , Ortega Arturo 
Published: November 2007

AbstractThe biochemical effects triggered by the action of glutamate, the main excitatory amino acid, on a specialized type of glia cells, Bergmann glial cells of the cerebellum, are a model system with which to study glia–neuronal interactions. Neuron to Bergmann glia signaling is involved in early stages of development, mainly in cell migration and synaptogenesis. Later, in adulthood, these cells have an important role in the maintenance and proper function of the synapses that they surround. Major molecular targets of this cellular interplay are glial glutamate receptors and transporters, both of which sense synaptic activity. Glutamate receptors trigger a complex network of signaling cascades that involve Ca2+ influx and lead to a differential gene-expression pattern. In contrast, Bergmann glia glutamate transporters participate in the removal of the neurotransmitter from the synaptic cleft and act also as signal transducers that regulate, in the short term, their own activity. These exciting findings strengthen the concept of active participation of glial cells in synaptic transmission and the involvement of neuron–glia circuits in the processing of brain information.
Ornamentation in Irish Fiddling: Eileen Ivers as a Case Study
Authors: SLOTTOW STEPHEN P. 
Published: November 2007

AbstractThis article is a study of ornamentation in the fiddling of Eileen Ivers. Ivers grew up in the Bronx, studied with Limerick-born fiddler Martin Mulvihill, and has since become one of the most well-known of contemporary Irish fiddlers. Although Ivers is known primarily for her Irish fusion playing style, her more traditional core style is reflected in this article, which is based on a series of interview-lessons. The types of ornaments and their placement, combination, function, and effect in Ivers's performance of Irish dance music are discussed.
Permeabilization of Phospholipid Bilayer Membranes Induced by Gas‐Liquid Flow in an Airlift Bubble Column
Authors: Yoshimoto Makoto , Monden Miyuki , Jiang Zhongwei , Nakao Katsumi 
Published: November 2007

AbstractThe permeability of 5(6)‐carboxyfluorescein (CF) through the phospholipid bilayer membranes was measured by using the system in which the CF‐containing phospholipid vesicles (liposomes) were suspended in the gas‐liquid flow in an external loop airlift bubble column. The airlift was operated at various superficial gas velocities UG up to 2.4 cm/s at 25 and 40 °C. The CF‐containing liposomes composed of POPC (1‐palmitoyl‐2‐oleoyl‐sn‐glycero‐3‐phosphocholine) had the nominal diameters of 50, 100, and 200 nm. The 50– and 100‐nm liposomes were stable at 40 °C for 5 h even at a high UG value of 2.4 cm/s based on the observed turbidity of the liposome suspension in the airlift. On the other hand, the 200‐nm liposomes were stable at a low UG value of 1.4 cm/s, although a progressive decrease in size of the liposomes was implied at the high UG value of 2.4 cm/s. The permeability coefficient PCF of CF through the lipid membrane of the 100‐nm liposomes was significantly increased with increasing UG at a high temperature of 40 °C, while at a low temperature of 25 °C the PCF value was little dependent on UG. As a typical result on the above liposomes, the PCF value (9.2 × 10−11 cm/s) at 40 °C and UG = 2.4 cm/s in the airlift was more than 15 times larger than that at 25 °C in the static liquid corresponding to UG = 0. In addition, the dependence of the PCF value on UG at 40 °C became more significant with increasing the size of liposomes suspended. The results obtained revealed that the permeability of the liposome membranes could be regulated by suspending the liposomes in the gas‐liquid flow in the airlift without modulating the membrane composition of liposomes.
Thorsellia anophelis is the dominant bacterium in a Kenyan population of adult Anopheles gambiae mosquitoes
Authors: Briones Aurelio M , Shililu Josephat , Githure John , Novak Robert , Raskin Lutgarde 
Published: November 2007

Abstract
Anopheles gambiae mosquitoes are not known to harbor endosymbiotic bacteria. Here we show, using nucleic acid-based methods, that 16S rRNA gene sequences specific to a recently described mosquito midgut bacterium, Thorsellia anophelis, is predominant in the midgut of adult An. gambiae s.l. mosquitoes captured in residences in central Kenya, and also occurs in the aquatic rice paddy environment nearby. PCR consistently detected T. anophelis in the surface microlayer of rice paddies, which is also consistent with the surface-feeding behavior of A. gambiae s.l. larvae. Phylogenetic analysis of cloned environmental 16S rRNA genes identified four major Thorsellia lineages, which are closely affiliated to an insect endosymbiont of the genus Arsenophonus. Physiological characterizations support the hypothesis that T. anophelis is well adapted to the female anopheline midgut by utilizing blood and tolerating the alkaline conditions in this environment. The results suggest that aquatically derived bacteria such as T. anophelis can persist through mosquito metamorphosis and become well-established in the adult mosquito midgut.
Interspecific competition and siderophore-mediated cooperation in Pseudomonas aeruginosa
Authors: Harrison Freya , Paul Jon , Massey Ruth C , Buckling Angus 
Published: November 2007

Abstract
Both intra- and interspecific interactions between microbes are likely to play an important role in determining the severity of microbial infections. Here, we study the impact of interactions between coinfecting opportunistic pathogens Staphylococcus aureus and Pseudomonas aeruginosa on both phenotypic and genetic changes in a P. aeruginosa social trait, the production of iron-scavenging siderophores. Siderophores are facultatively upregulated in response to iron limitation and play a key role in determining the virulence of microbial infections. Siderophore production is metabolically expensive to individual producers but benefits the group as a whole because siderophores can be used by all cells in the vicinity with siderophore receptors. Hence, populations of siderophore producers can be invaded by nonproducing cheats. Previous work has shown that P. aeruginosa can lyse S. aureus, supplying a source of free iron. We therefore hypothesized that the presence of S. aureus might result in facultative downregulation of siderophore production, and in turn, reduced selection for siderophore cheats. We tested this hypothesis by evolving P. aeruginosa in the presence and absence of free iron and S. aureus, in a fully factorial design. Iron had the expected effect: siderophore production was downregulated and cheats evolved less readily, but the presence of S. aureus instead increased facultative siderophore production and selection for cheats. This is probably because the S. aureus had the net effect of competing for iron, rather than acting as an iron source. This study demonstrates that interspecific competition can have a marked effect on intraspecific social interactions.
The twin-arginine transport system: moving folded proteins across membranes
Authors: Sargent F. 
Published: November 2007

The Tat (twin-arginine transport) pathway is a protein-targeting system dedicated to the transmembrane translocation of fully folded proteins. This system is highly prevalent in the cytoplasmic membranes of bacteria and archaea, and is also found in the thylakoid membranes of plant chloroplasts and possibly also in the inner membrane of plant mitochondria. Proteins are targeted to a membrane-embedded Tat translocase by specialized N-terminal twin-arginine signal peptides bearing an SRRXFLK amino acid motif. The genes encoding components of the Tat translocase were discovered approx. 10 years ago, and, since then, research in this area has expanded on a global scale. In this review, the key discoveries in this field are summarized, and recent studies of bacterial twin-arginine signal-peptide-binding proteins are discussed.
Visualization of protein interactions inside the secretory pathway
Authors: Nyfeler B. , Hauri H.-P. 
Published: November 2007

The ER (endoplasmic reticulum) is a major protein folding and modification organelle. In its lumen, the ER processes a third of all newly synthesized proteins. To accomplish this task, numerous resident proteins capture the nascent and newly synthesized proteins. The underlying luminal protein–protein interactions, however, are inherently difficult to analyse, mainly due to their transient nature and the rather specialized environment of the ER. To overcome these limitations, we developed a PCA (protein fragment complementation assay) based on the citrine variant of YFP (yellow fluorescent protein). YFP PCA was successfully applied to visualize the protein interactions of the cargo transport receptor ERGIC-53 (endoplasmic reticulum–Golgi intermediate compartment protein of 53 kDa) with its luminal interaction partner MCFD2 (multiple coagulation factor deficiency protein 2) and its cargo proteins cathepsin Z and cathepsin C in a specific manner. With the prospect of screening cDNA libraries for novel protein–protein interactions, YFP PCA is a promising emerging technique for mapping protein interactions inside the secretory pathway in a genome-wide setting.
Ion channels in epilepsy
Authors: Mizielinska S.M. 
Published: November 2007

Neuronal excitability is determined by the flux of ions through ion channels. Many types of ion channels are expressed in the central nervous system, each responsible for its own aspect of neuronal excitability, from postsynaptic depolarization to action potential generation to neurotransmitter release. These mechanisms are tightly regulated to create a balance between excitation and inhibition. Disruption of this balance is thought to be key in many neurological disorders, including epilepsy syndromes. More and more ion channel mutations are being identified through genetic studies; however, their incidence is still small, suggesting the presence of undiscovered mutations or other causative mechanisms. Understanding wild-type channel function during epileptic activity may also provide vital insights into the remaining idiopathic epilepsies and provide targets for future antiepileptic drugs.
PERK in the life and death of the pancreatic β-cell
Authors: Herbert T.P. 
Published: November 2007

To ensure cellular survival to ER (endoplasmic reticulum) stress, PERK [PKR (double-stranded-RNA-dependent protein kinase)-like ER kinase], an ER transmembrane kinase, is activated as part of the unfolded protein response. PERK is highly expressed in pancreatic β-cells and is essential in the β-cell's development, differentiation and function. However, chronic activation of PERK can induce cell death, and its activation has been implicated in both Type 1 and Type 2 diabetes. This short review aims to provide an insight into our current understanding of the role of PERK in the life and death of the β-cell.
Amino acid transporters and nutrient-sensing mechanisms: new targets for treating insulin-linked disorders?
Authors: Reynolds B. , Laynes R. , Ögmundsdóttir M.H. , Boyd C.A.R. , Goberdhan D.C.I. 
Published: November 2007

The IIS (insulin/IGF (insulin-like growth factor) signalling) cascade has an important role in regulating normal development and physiology, as evidenced by its effects in a host of major human diseases including cancer, Type 2 diabetes and neurodegeneration. Recently, it has become clear that multiple types of local nutrient-sensing mechanisms have an impact on cellular insulin-sensitivity through the downstream kinase TOR (target of rapamycin). In vivo analysis in flies has surprisingly highlighted PATs (proton-assisted amino acid transporters) as having a uniquely potent role in regulating IIS/TOR activity and growth, potentially via a novel signalling mechanism. Other molecules such as the heterodimeric amino acid transporter, CD98, which provides the principal route for cellular uptake of leucine, an amino acid implicated in regulating TOR, also appear to have important effects. As our understanding of how nutrient sensing has an impact on IIS/TOR increases, novel targets to modulate aberrant IIS in disease are likely to emerge, which could complement current strategies designed to block kinases in this pathway.
Nitric oxide and respiratory rhythm in mammals: a new modulator of phase transition?
Authors: Pierrefiche O. , Abdala A.P.L. , Paton J.F.R. 
Published: November 2007

NO (nitric oxide) modulates several central pattern generators, but its role in respiratory rhythmogenesis and its mode of action on medullary respiratory neurons during normoxia are unknown. We analysed the actions of NO on the mammalian respiratory network at the system and cellular levels. Given systemically, the NO donor diethylamine NONOate increased post-inspiratory duration in vagus, phrenic and hypoglossal nerves, whereas blockade of NO generation with L-NAME (NG-nitro-L-arginine methyl ester) produced the opposite response. At the cellular level, we pressure-ejected the NO donor on to respiratory neurons. NO had both inhibitory and excitatory effects on all types of respiratory neurons. Inhibitory effects involved soluble guanylate cyclase, as they were blocked with ODQ (1H-[1,2,4]oxadiazolo[4,3a]quinoxalin-1-one), whereas excitations were antagonized by uric acid and possibly mediated via peroxynitrite. Importantly, NO facilitated both GABA (γ-aminobutyric acid)- and NMDA (N-methyl-D-aspartate)-induced neuronal responses, but this was restricted to post-inspiratory and pre-inspiratory neurons; other neuron types showed additive effects only. Our results support NO as modulator of centrally generated respiratory activity and specifically of ligand-mediated responses in respiratory neuron types involved in respiratory phase transition.
IL-6 signalling in exercise and disease
Authors: Pedersen B.K. 
Published: November 2007

Low-grade chronic inflammation is a feature of Type 2 diabetes and appears to play a pathogenetic role in insulin resistance. It is well known that cytokines, besides their immunoregulatory roles, are important players in metabolism. Moreover, it has become evident that skeletal muscles express several cytokines, which belong to distinct cytokine classes. IL-6 (interleukin-6) is a pleiotropic cytokine produced by virtually all multinucleated cells including skeletal myocytes where it is produced in response to contraction. IL-6 is subsequently released into the circulation, where it works in a hormone-like fashion to induce lipolysis and fat oxidation. In more recent experiments, it has been shown that IL-6 infusion increases glucose disposal during a hyperinsulinaemic euglycaemic clamp in healthy humans. IL-6 treatment of myotubes increases fatty acid oxidation, basal and insulin-stimulated glucose uptake and translocation of GLUT4 to the plasma membrane. Furthermore, IL-6 rapidly and markedly increases AMPK (AMP-activated protein kinase) and the metabolic effects of IL-6 were abrogated in AMPK dominant negative-infected cells. Finally, IL-6 mediates anti-inflammatory effects by stimulating the production of anti-inflammatory cytokines and by suppressing TNFα (tumour necrosis factor α) production. We suggest that IL-6 and other muscle-derived cytokines (myokines) may play a role in defending Type 2 diabetes.
Tuberculosis: evolution in millennia and minutes
Authors: Gillespie S.H. 
Published: November 2007

Tuberculosis remains a global public health threat: the causative organism, Mycobacterium tuberculosis, was once thought to show little genetic variation, but research in the last 10 years has demonstrated an ability to change in a series of different time frames. Related species of mycobacteria have undergone evolution by deletion of segments of DNA, allowing Mycobacterium bovis and other species to emerge from the M. tuberculosis complex, disproving the previously accepted theories. Deletions also affect the pathogenic potential of different lineages of M. tuberculosis. Over shorter time periods genetic variation is achieved by the movement of insertion sequences such as IS6110. Some lineages identified by this means are over-represented in patient populations, suggesting a genetic advantage, although the mechanism for this is not yet apparent. M. tuberculosis must also adapt to host and antibiotic selection pressure, and this is achieved by point mutations. Almost all antibiotic resistance emerges in this way, and data from clinical and in vitro studies indicate that M. tuberculosis exists with pre-existent mutants that remain as a small proportion of the population because of fitness deficits. Under certain physiological conditions, these rarer mutants may be favoured and, when antibiotic selection pressure is applied, will rise to dominate the bacterial population. M. tuberculosis is a highly effective pathogen that has caused disease in human populations for millennia. We are now starting to understand some of the genetic mechanisms behind this phenomenon.
The PCSK9 gene R46L variant is associated with lower plasma lipid levels and cardiovascular risk in healthy U.K. men
Authors: Scartezini Marileia , Hubbart Christina , Whittall Ros A. , Cooper Jackie A. , Neil Andrew H. W. , Humphries Steve E. 
Published: November 2007

In the present study, we have determined the relative frequency of the R46L, I474V and E670G variants in the PCSK9 (protein convertase subtilisin/kexin type 9) gene and its association with plasma lipid levels and CHD (coronary heart disease) in healthy U.K. men and patients with clinically defined definite FH (familial hypercholesterolaemia). Genotypes were determined using PCR and restriction enzyme digestion in 2444 healthy middle-aged (50–61 years) men from the prospective NPHSII (Second Northwick Park Heart Study), with 275 CHD events (15 years of follow-up), and in 597 U.K. FH patients from the Simon Broome Register. In the NPHSII healthy men, the R46L genotype distribution was in Hardy–Weinberg equilibrium and the frequency of 46L was 0.010 [95% CI (confidence interval), 0.007–0.013], with one man homozygous for the 46L allele. There was significant association of the 46L allele with lower mean (S.D.) total cholesterol [5.74 (1.01) mmol/l for RR compared with 5.26±1.03 mmol/l for RL; P=0.001], apolipoprotein B [0.87 (0.24) g/l for RR compared with 0.75 (0.26) g/l for RL; P&lt;0.0001] and low-density lipoprotein cholesterol [4.01 (0.95) mmol/l for RR compared with 3.62 (0.97) mmol/l for RL; P=0.02]) levels, after adjustment for age, general medical practice, smoking, body mass index and systolic blood pressure. As expected, 46L carriers had a low risk of definite or possible CHD [hazard ratio, 0.46 (95% CI, 0.11–1.84)], but this was not statistically significant (P=0.27). Two other common PCSK9 variants I474V [V allele frequency, 0.179 (95% CI, 0.17–0.19)] and E670G [G allele frequency, 0.034 (CI, 0.03–0.04)] were not associated with any significant effects on lipid levels or CHD risk. In FH patients, the frequency of 46L was 0.003 (95% CI, 0.00–0.01), which was significantly lower (P=0.037) than the healthy subjects. In the four FH patients carrying 46L, mean untreated total cholesterol levels were not different (P=0.91) in carriers and non-carriers (median, 10.3 mmol/l compared with 10.2 mmol/l respectively, after adjustment for age, gender and mutation type). In conclusion, the PCSK9 46L allele is more frequent in healthy U.K. men than in FH patients and is strongly associated with a protective plasma lipid profile risk for CHD. Its low frequency (approx. 2% carriers) means that it does not make a major contribution to determining population CHD risk in the U.K.
Symmetry breaking and quantum correlations in finite systems: studies of quantum dots and ultracold Bose gases and related nuclear and chemical methods
Authors: Yannouleas Constantine , Landman Uzi 
Published: November 2007

Investigations of emergent symmetry breaking phenomena occurring in small finite-size systems are reviewed, with a focus on the strongly correlated regime of electrons in two-dimensional semiconductor quantum dots and trapped ultracold bosonic atoms in harmonic traps. Throughout the review we emphasize universal aspects and similarities of symmetry breaking found in these systems, as well as in more traditional fields like nuclear physics and quantum chemistry, which are characterized by very different interparticle forces. A unified description of strongly correlated phenomena in finite systems of repelling particles (whether fermions or bosons) is presented through the development of a two-step method of symmetry breaking at the unrestricted Hartree–Fock level and of subsequent symmetry restoration via post Hartree–Fock projection techniques. Quantitative and qualitative aspects of the two-step method are treated and validated by exact diagonalization calculations.Strongly-correlated phenomena emerging from symmetry breaking include the following.Chemical bonding, dissociation and entanglement (at zero and finite magnetic fields) in quantum dot molecules and in pinned electron molecular dimers formed within a single anisotropic quantum dot, with potential technological applications to solid-state quantum-computing devices.Electron crystallization, with particle localization on the vertices of concentric polygonal rings, and formation of rotating electron molecules (REMs) in circular quantum dots. Such electron molecules exhibit ro-vibrational excitation spectra, in analogy with natural molecules.At high magnetic fields, the REMs are described by parameter-free analytic wave functions, which are an alternative to the Laughlin and composite-fermion approaches, offering a new point of view of the fractional quantum Hall regime in quantum dots (with possible implications for the thermodynamic limit).Crystalline phases of strongly repelling bosons. In rotating traps and in analogy with the REMs, such repelling bosons form rotating boson molecules (RBMs). For a small number of bosons, the RBMs are energetically favored compared with the Gross–Pitaevskii solutions describing vortex formation.We discuss the present status concerning experimental signatures of such strongly correlated states, in view of the promising outlook created by the latest experimental improvements that are achieving unprecedented control over the range and strength of interparticle interactions.