bluuebunny/crossref_metadata_2025 huggingface dataset:
Coupling a sensory hair-cell bundle to cyber clones enhances nonlinear amplification
Authors: Barral Jérémie , Dierkes Kai , Lindner Benjamin , Jülicher Frank , Martin Pascal
Published: April 2010

The vertebrate ear benefits from nonlinear mechanical amplification to operate over a vast range of sound intensities. The amplificatory process is thought to emerge from active force production by sensory hair cells. The mechano-sensory hair bundle that protrudes from the apical surface of each hair cell can oscillate spontaneously and function as a frequency-selective, nonlinear amplifier. Intrinsic fluctuations, however, jostle the response of a single hair bundle to weak stimuli and seriously limit amplification. Most hair bundles are mechanically coupled by overlying gelatinous structures. Here, we assayed the effects of mechanical coupling on the hair-bundle amplifier by combining dynamic force clamp of a hair bundle from the bullfrog’s saccule with real-time stochastic simulations of hair-bundle mechanics. This setup couples the hair bundle to two virtual hair bundles, called cyber clones, and mimics a situation in which the hair bundle is elastically linked to two neighbors with similar characteristics. We found that coupling increased the coherence of spontaneous hair-bundle oscillations. By effectively reducing noise, the synergic interplay between the hair bundle and its cyber clones also enhanced amplification of sinusoidal stimuli. All observed effects of coupling were in quantitative agreement with simulations. We argue that the auditory amplifier relies on hair-bundle cooperation to overcome intrinsic noise limitations and achieve high sensitivity and sharp frequency selectivity.
X-ray insights into star and planet formation
Authors: Feigelson Eric D.
Published: April 2010

Although stars and planets form in cold environments, X-rays are produced in abundance by young stars. This review examines the implications of stellar X-rays for star and planet formation studies, highlighting the contributions of NASA’s (National Aeronautics and Space Administration) Chandra X-ray Observatory. Seven topics are covered: X-rays from protostellar outflow shocks, X-rays from the youngest protostars, the stellar initial mass function, the structure of young stellar clusters, the fate of massive stellar winds, X-ray irradiation of protoplanetary disks, and X-ray flare effects on ancient meteorites. Chandra observations of star-forming regions often show dramatic star clusters, powerful magnetic reconnection flares, and parsec-scale diffuse plasma. X-ray selected samples of premain sequence stars significantly advance studies of star cluster formation, the stellar initial mass function, triggered star-formation processes, and protoplanetary disk evolution. Although X-rays themselves may not play a critical role in the physics of star formation, they likely have important effects on protoplanetary disks by heating and ionizing disk gases.
c-Cbl deficiency leads to diminished lymphocyte development and functions in an age-dependent manner
Authors: Rathinam Chozhavendan , Flavell Richard A.
Published: April 2010

Aging is broadly defined as a progressive decline of tissue and organ functions due to deregulation of various cell intrinsic and extrinsic factors. In the immune system, aging preferentially affects lymphopoiesis and thus results in the reduced competence of the adaptive immune system in the elderly. Despite recent discoveries that shed light on the molecular basis of aging, pathways that lead to diminished lymphoid development in aging individuals remain largely unknown. In the present study, we document that a deficiency of the E3 ubiquitin ligase c-Cbl in lymphocytes results in an age-dependent lymphopenia. c-Cbl-deficient mice show normal frequencies of lymphocytes at 12 weeks of age; however, their development and functions were remarkably diminished at 24 weeks after birth. Intriguingly, c-Cbl mutant lymphocytes displayed increased responses to IL7 in vitro and failed to down-regulate surface levels of IL7Rα. Further, our biochemical studies have identified an interaction of c-Cbl with IL7Rα and have unraveled the involvement of c-Cbl in the ubiquitylation of IL7Rα. In essence, our studies demonstrate that a lack of signaling events mediated by c-Cbl might result in diminished lymphocyte development and functions, particularly, at the later stages of life.
Anomalous expansion of the copper-apical-oxygen distance in superconducting cuprate bilayers
Authors: Zhou Hua , Yacoby Yizhak , Butko Vladimir Y. , Logvenov Gennady , Božović Ivan , Pindak Ron
Published: April 2010

We have introduced an improved x-ray phase-retrieval method with unprecedented speed of convergence and precision, and used it to determine with sub-Ångstrom resolution the complete atomic structure of epitaxial La

2-
x

Sr

x

CuO
4
ultrathin films. We focus on superconducting heterostructures built from constituent materials that are not superconducting in bulk samples. Single-phase metallic or superconducting films are also studied for comparison. The results show that this phase-retrieval diffraction method enables accurate measurement of structural modifications in near-surface layers, which may be critically important for elucidation of surface-sensitive experiments. Specifically we find that, while the copper-apical-oxygen distance remains approximately constant in single-phase films, it shows a dramatic increase from the metallic-insulating interface of the bilayer towards the surface by as much as 0.45 Å. The apical-oxygen displacement is known to have a profound effect on the superconducting transition temperature.
Phosphodiesterase 11A in brain is enriched in ventral hippocampus and deletion causes psychiatric disease-related phenotypes
Authors: Kelly Michele P. , Logue Sheree F. , Brennan Julie , Day Jonathon P. , Lakkaraju Subha , Jiang Lixin , Zhong Xiaotian , Tam May , Sukoff Rizzo Stacey J. , Platt Brian J. , Dwyer Jason M. , Neal Sarah , Pulito Virginia L. , Agostino Michael J. , Grauer Steven M. , Navarra Rachel L. , Kelley Cody , Comery Thomas A. , Murrills Richard J. , Houslay Miles D. , Brandon Nicholas J.
Published: April 2010

Phosphodiesterase 11A (PDE11A) is the most recently identified family of phosphodiesterases (PDEs), the only known enzymes to break down cyclic nucleotides. The tissue expression profile of this dual specificity PDE is controversial, and little is understood of its biological function, particularly in the brain. We seek here to determine if PDE11A is expressed in the brain and to understand its function, using PDE11A
−/−
knockout (KO) mice. We show that PDE11A mRNA and protein are largely restricted to hippocampus CA1, subiculum, and the amygdalohippocampal area, with a two- to threefold enrichment in the ventral vs. dorsal hippocampus, equal distribution between cytosolic and membrane fractions, and increasing levels of protein expression from postnatal day 7 through adulthood. Interestingly, PDE11A KO mice show subtle psychiatric-disease–related deficits, including hyperactivity in an open field, increased sensitivity to the glutamate
N
-methyl-
D
-aspartate receptor antagonist MK-801, as well as deficits in social behaviors (social odor recognition memory and social avoidance). In addition, PDE11A KO mice show enlarged lateral ventricles and increased activity in CA1 (as per increased Arc mRNA), phenotypes associated with psychiatric disease. The increased sensitivity to MK-801 exhibited by PDE11A KO mice may be explained by the biochemical dysregulation observed around the glutamate α-amino-3-hydroxy-5-methyl-4-isozazolepropionic (AMPA) receptor, including decreased levels of phosphorylated-GluR1 at Ser845 and the prototypical transmembrane AMPA-receptor–associated proteins stargazin (γ2) and γ8. Together, our data provide convincing evidence that PDE11A expression is restricted in the brain but plays a significant role in regulating brain function.
Grand unification of neutron stars
Authors: Kaspi Victoria M.
Published: April 2010

The last decade has shown us that the observational properties of neutron stars are remarkably diverse. From magnetars to rotating radio transients, from radio pulsars to isolated neutron stars, from central compact objects to millisecond pulsars, observational manifestations of neutron stars are surprisingly varied, with most properties totally unpredicted. The challenge is to establish an overarching physical theory of neutron stars and their birth properties that can explain this great diversity. Here I survey the disparate neutron stars classes, describe their properties, and highlight results made possible by the Chandra X-Ray Observatory, in celebration of its 10th anniversary. Finally, I describe the current status of efforts at physical “grand unification” of this wealth of observational phenomena, and comment on possibilities for Chandra’s next decade in this field.
Phosphorylation-induced structural changes in smooth muscle myosin regulatory light chain
Authors: Kast David , Espinoza-Fonseca L. Michel , Yi Christina , Thomas David D.
Published: April 2010

We have performed complementary time-resolved fluorescence resonance energy transfer (TR-FRET) experiments and molecular dynamics (MD) simulations to elucidate structural changes in the phosphorylation domain (PD) of smooth muscle regulatory light chain (RLC) bound to myosin. PD is absent in crystal structures, leaving uncertainty about the mechanism of regulation. Donor-acceptor pairs of probes were attached to three site-directed di-Cys mutants of RLC, each having one Cys at position 129 in the C-terminal lobe and the other at position 2, 3, or 7 in the N-terminal PD. Labeled RLC was reconstituted onto myosin subfragment 1 (S1). TR-FRET resolved two simultaneously populated structural states of RLC, closed and open, in both unphosphorylated and phosphorylated biochemical states. All three FRET pairs show that phosphorylation shifts the equilibrium toward the open state, increasing its mol fraction by ∼20%. MD simulations agree with experiments in remarkable detail, confirming the coexistence of two structural states, with phosphorylation shifting the system toward the more dynamic open structural state. This agreement between experiment and simulation validates the additional structural details provided by MD simulations: In the closed state, PD is bent onto the surface of the C-terminal lobe, stabilized by interdomain salt bridges. In the open state, PD is more helical and straight, resides farther from the C-terminal lobe, and is stabilized by an intradomain salt bridge. The result is a vivid atomic-resolution visualization of the first step in the molecular mechanism by which phosphorylation activates smooth muscle.
Postreplication gaps at UV lesions are signals for checkpoint activation
Authors: Callegari A. John , Clark Emily , Pneuman Amanda , Kelly Thomas J.
Published: April 2010

Exposure of eukaryotic cells to UV light induces a checkpoint response that delays cell-cycle progression after cells enter S phase. It has been hypothesized that this checkpoint response provides time for repair by signaling the presence of structures generated when the replication fork encounters UV-induced DNA damage. To gain insight into the nature of the signaling structures, we used time-lapse microscopy to determine the effects of deficiencies in translesion DNA polymerases on the checkpoint response of the fission yeast
Schizosaccharomyces pombe
. We found that disruption of the genes encoding translesion DNA polymerases Polκ and Polη significantly prolonged the checkpoint response, indicating that the substrates of these enzymes are signals for checkpoint activation. Surprisingly, we found no evidence that the translesion polymerases Rev1 and Polζ repair structures that are recognized by the checkpoint despite their role in maintaining viability after UV irradiation. Quantitative flow cytometry revealed that cells lacking translesion polymerases replicate UV-damaged DNA at the same rate at WT cells, indicating that the enhanced checkpoint response of cells lacking Polκ and Polη is not the result of stalled replication forks. These observations support a model in which postreplication DNA gaps with unrepaired UV lesions in the template strand act both as substrates for translesion polymerases and as signals for checkpoint activation.
Inference of combinatorial Boolean rules of synergistic gene sets from cancer microarray datasets
Authors: Park Inho , Lee Kwang H. , Lee Doheon
Published: April 2010

Motivation: Gene set analysis has become an important tool for the functional interpretation of high-throughput gene expression datasets. Moreover, pattern analyses based on inferred gene set activities of individual samples have shown the ability to identify more robust disease signatures than individual gene-based pattern analyses. Although a number of approaches have been proposed for gene set-based pattern analysis, the combinatorial influence of deregulated gene sets on disease phenotype classification has not been studied sufficiently.

Results: We propose a new approach for inferring combinatorial Boolean rules of gene sets for a better understanding of cancer transcriptome and cancer classification. To reduce the search space of the possible Boolean rules, we identify small groups of gene sets that synergistically contribute to the classification of samples into their corresponding phenotypic groups (such as normal and cancer). We then measure the significance of the candidate Boolean rules derived from each group of gene sets; the level of significance is based on the class entropy of the samples selected in accordance with the rules. By applying the present approach to publicly available prostate cancer datasets, we identified 72 significant Boolean rules. Finally, we discuss several identified Boolean rules, such as the rule of glutathione metabolism (down) and prostaglandin synthesis regulation (down), which are consistent with known prostate cancer biology.

Availability: Scripts written in Python and R are available at http://biosoft.kaist.ac.kr/∼ihpark/. The refined gene sets and the full list of the identified Boolean rules are provided in the Supplementary Material.

Contact:  khlee@biosoft.kaist.ac.kr; dhlee@biosoft.kaist.ac.kr

Supplementary information:  Supplementary data are available at Bioinformatics online.
Low Reticulocyte Hemoglobin Content Is Associated with a Higher Blood Transfusion Rate in Critically Ill Patients
Authors: Fernandez Rafael , Tubau Isabel , Masip Jordi , Muñoz Luz , Roig Inmaculada , Artigas Antonio
Published: April 2010

Background

Intensive care unit (ICU) patients often need blood transfusion, but no reliable predictors of transfusion requirements are available at ICU admission. The authors hypothesized that ICU patients with functional iron deficiency may be at higher risk for developing anemia, requiring blood transfusion. Their objective was to determine whether low reticulocyte hemoglobin content (CHr) was associated with transfusion requirements in ICU patients.

Methods

This is a prospective cohort study in a general ICU. The authors studied 62 patients, after excluding those transfused on or before ICU admission. The authors recorded age, diagnosis, severity score, presence of sepsis, ICU complications, ICU treatments, and transfusion-free interval. Threshold for low CHr was 29 pg. The authors also recorded ICU and hospital outcome. The statistical analysis included Cox proportional hazard function for transfusion.

Results

Twenty-three patients (37%) presented with low CHr on ICU admission and tended to be sicker and more likely to have sepsis than those with normal CHr. They were also more prone to complications, particularly acute renal failure (39 vs. 13% P = 0.02) and ICU-acquired infection (30 vs. 10% P = 0.04). The overall transfusion rate was 22.6%, being higher in low-CHr patients than in normal-CHr patients (39.1 vs. 12.8%, P = 0.02). After adjusting for severity of illness, age, trauma, and hemoglobin level, low CHr remained significantly associated with transfusion, with a hazard ratio of 3.6 (95% CI, 1.2-10.7; P = 0.02). Median ICU stay was also longer in patients with low CHr (8 vs. 5 days, P = 0.01). Differences in mortality did not reach statistical significance.

Conclusion

Low CHr is common at ICU admission and is associated with higher transfusion requirements.
DNA barcodes reveal species-specific mercury levels in tuna sushi that pose a health risk to consumers
Authors: Lowenstein Jacob H. , Burger Joanna , Jeitner Christian W. , Amato George , Kolokotronis Sergios-Orestis , Gochfeld Michael
Published: April 2010

Excessive ingestion of mercury—a health hazard associated with consuming predatory fishes—damages neurological, sensory-motor and cardiovascular functioning. The mercury levels found in Bigeye Tuna (
Thunnus obesus
) and bluefin tuna species (
Thunnus maccoyii
,
Thunnus orientalis
, and
Thunnus thynnus
), exceed or approach levels permissible by Canada, the European Union, Japan, the US, and the World Health Organization. We used DNA barcodes to identify tuna sushi samples analysed for mercury and demonstrate that the ability to identify cryptic samples in the market place allows regulatory agencies to more accurately measure the risk faced by fish consumers and enact policies that better safeguard their health.
High-titre retroviral vector system for efficient gene delivery into human and mouse cells of haematopoietic and lymphocytic lineages
Authors: Wu Chengxiang , Lu Yuanan
Published: April 2010

Genetically modified cells of haematopoietic and lymphocytic lineages could provide potentially curative treatments for a wide range of inherited and acquired diseases. However, this application is limited in mouse models by the low efficiency of lentiviral vectors. To facilitate the rapid production of high-titre helper-free retroviral vectors for enhanced gene delivery, multiple modifications to a prototype moloney murine leukemia virus (MoMLV)-derived vector system were made including adaptation of the vector system to simian virus 40ori/T antigen-mediated episomal replication in packaging cells, replacement of the MoMLV 5′ U3 promoter with a series of stronger composite promoters and addition of an extra polyadenylation signal downstream of the 3′ long terminal repeat. These modifications enhanced vector production by 2–3 logs. High-titre vector stocks were tested for their ability to infect a variety of cells derived from humans and mice, including primary monocyte-derived macrophage cultures. Whilst the lentiviral vector was significantly restricted at the integration level, the MoMLV-based vector showed effective gene transduction of mouse cells. This high-titre retroviral vector system represents a useful tool for efficient gene delivery into human and mouse haematopoietic and lymphocytic cells, with particular application in mice as a small animal model for novel gene therapy tests.
Inhibition of host innate immune responses and pathogenicity of recombinant Newcastle disease viruses expressing NS1 genes of influenza A viruses
Authors: Kim Shin-Hee , Samal Siba K.
Published: April 2010

The NS1 protein has been associated with the virulence of influenza A viruses. To evaluate the role of the NS1 protein in pathogenicity of pandemic H5N1 avian influenza and H1N1 2009 influenza viruses, recombinant Newcastle disease viruses (rNDVs) expressing NS1 proteins were generated. Expression of the NS1 proteins resulted in inhibition of host innate immune responses (beta interferon and protein kinase R production). In addition, the NS1 proteins were localized predominantly in the nucleus of virus-infected cells. Consequently, expression of the NS1 protein contributed to an increase in pathogenicity of rNDV in chickens. In particular, mutational analysis of H5N1 NS1 protein indicated that both the RNA-binding and effector domains affect virus pathogenicity synergistically. Our study also demonstrated that expression of H1N1/09 NS1 resulted in enhanced replication of rNDV in human cells, indicating that function of the NS1 proteins can be host-species-specific.
Structures of the PKC-ι kinase domain in its ATP-bound and apo forms reveal defined structures of residues 533–551 in the C-terminal tail and their roles in ATP binding
Authors: Takimura Tetsuo , Kamata Kenji , Fukasawa Kazuhiro , Ohsawa Hirokazu , Komatani Hideya , Yoshizumi Takashi , Takahashi Ikuko , Kotani Hidehito , Iwasawa Yoshikazu
Published: April 2010

Protein kinase C (PKC) plays an essential role in a wide range of cellular functions. Although crystal structures of the PKC-θ, PKC-ι and PKC-βII kinase domains have previously been determined in complexes with small-molecule inhibitors, no structure of a PKC–substrate complex has been determined. In the previously determined PKC-ι complex, residues 533–551 in the C-terminal tail were disordered. In the present study, crystal structures of the PKC-ι kinase domain in its ATP-bound and apo forms were determined at 2.1 and 2.0 Å resolution, respectively. In the ATP complex, the electron density of all of the C-terminal tail residues was well defined. In the structure, the side chain of Phe543 protrudes into the ATP-binding pocket to make van der Waals interactions with the adenine moiety of ATP; this is also observed in other AGC kinase structures such as binary and ternary substrate complexes of PKA and AKT. In addition to this interaction, the newly defined residues around the turn motif make multiple hydrogen bonds to glycine-rich-loop residues. These interactions reduce the flexibility of the glycine-rich loop, which is organized for ATP binding, and the resulting structure promotes an ATP conformation that is suitable for the subsequent phosphoryl transfer. In the case of the apo form, the structure and interaction mode of the C-terminal tail of PKC-ι are essentially identical to those of the ATP complex. These results indicate that the protein structure is pre-organized before substrate binding to PKC-ι, which is different from the case of the prototypical AGC-branch kinase PKA.
Structure ofD-tyrosyl-tRNATyrdeacylase using home-source Cu Kα and moderate-quality iodide-SAD data: structural polymorphism and HEPES-bound enzyme states
Authors: Yogavel Manickam , Khan Sameena , Bhatt Tarun Kumar , Sharma Amit
Published: April 2010

D-Tyrosyl-tRNATyrdeacylase (DTD) is an editing enzyme that removes D-amino acids from mischarged tRNAs. The crystal structure ofPlasmodium falciparumDTD (PfDTD) was determined using the iodide-SAD phasing method. Iodide-derivatized PfDTD crystals were obtained using the quick cryo-soaking procedure in which native crystals were soaked for a short period of 10–30 s in cryoprotectant solution containing 0.2–1 MNaI. Iodide-SAD data sets were collected to 3.3 and 2.74 Å resolution from PfDTD crystals that belonged to two different space groups,P43andP1, using an in-house X-ray copper-anode source. This is the first report to detail structure solution using low iodide anomalous signal, modest resolution and redundancy and average solvent content for SAD phasing of 984 and 1312 amino acids in the triclinicP1 and tetragonalP43space groups, respectively. A total of 85% and 56% of the residues were automatically built into the iodide-phased electron-density maps usingPHENIX AutoBuild. The structure of HEPES-bound PfDTD was subsequently determined by molecular replacement and refined to 2.83 Å resolution. The crystals obtained from various batches of crystallization trials of PfDTD exhibited polymorphism in terms of belonging to different crystal forms and space groups. Even within a given crystal system the unit-cell parameters showed high non-isomorphism. These packing variations were exploited in order to conduct a systematic study of conformational changes in PfDTD. It is shown that the disposition of a ten-residue insertion loop affects packing within the PfDTD crystals and seems to determine the non-isomorphism in unit-cell parameters. By tracking the changes in PfDTD unit cells, it was possible to map conformational differences within PfDTD that may be of significance for enzyme activity.
Application of protein engineering to enhance crystallizability and improve crystal properties
Authors: Derewenda Zygmunt S.
Published: April 2010

Until recently, protein crystallization has mostly been regarded as a stochastic event over which the investigator has little or no control. With the dramatic technological advances in synchrotron-radiation sources and detectors and the equally impressive progress in crystallographic software, including automated model building and validation, crystallization has increasingly become the rate-limiting step in X-ray diffraction studies of macromolecules. However, with the advent of recombinant methods it has also become possible to engineer target proteins and their complexes for higher propensity to form crystals with desirable X-ray diffraction qualities. As most proteins that are under investigation today are obtained by heterologous overexpression, these techniques hold the promise of becoming routine tools with the potential to transform classical crystallization screening into a more rational high-success-rate approach. This article presents an overview of protein-engineering methods designed to enhance crystallizability and discusses a number of examples of their successful application.
Atomic resolution studies of carbonic anhydrase II
Authors: Behnke Craig A. , Le Trong Isolde , Godden Jeff W. , Merritt Ethan A. , Teller David C. , Bajorath Jürgen , Stenkamp Ronald E.
Published: April 2010

Carbonic anhydrase has been well studied structurally and functionally owing to its importance in respiration. A large number of X-ray crystallographic structures of carbonic anhydrase and its inhibitor complexes have been determined, some at atomic resolution. Structure determination of a sulfonamide-containing inhibitor complex has been carried out and the structure was refined at 0.9 Å resolution with anisotropic atomic displacement parameters to anRvalue of 0.141. The structure is similar to those of other carbonic anhydrase complexes, with the inhibitor providing a fourth nonprotein ligand to the active-site zinc. Comparison of this structure with 13 other atomic resolution (higher than 1.25 Å) isomorphous carbonic anhydrase structures provides a view of the structural similarity and variability in a series of crystal structures. At the center of the protein the structures superpose very well. The metal complexes superpose (with only two exceptions) with standard deviations of 0.01 Å in some zinc–protein and zinc–ligand bond lengths. In contrast, regions of structural variability are found on the protein surface, possibly owing to flexibility and disorder in the individual structures, differences in the chemical and crystalline environments or the different approaches used by different investigators to model weak or complicated electron-density maps. These findings suggest that care must be taken in interpreting structural details on protein surfaces on the basis of individual X-ray structures, even if atomic resolution data are available.
Characterization of four rice mutants with alterations in the defence response pathway
Authors: CAMPBELL M. A. , RONALD P. C.
Published: April 2010

A fast‐neutron mutagenized population of rice seedlings was screened with Magnaporthe grisea, the causal agent of rice blast disease, to identify mutants with alterations in the defence response. Three mutant lines, ebr1, ebr2 and ebr3 (enhanced blast resistance) were identified that display enhanced resistance to M. grisea. ebr1 and ebr3 also confer enhanced resistance to the bacterial pathogen Xanthomonas oryzae pv. oryzae (Xoo). ebr3 develops a lesion mimic (LM) phenotype upon inoculation with M. grisea, and the phenotype is also induced by a shift in environmental conditions. The fourth mutant line, ncr1 (necrosis in rice), has an LM phenotype under all conditions tested and lacks enhanced resistance to either M. grisea or Xoo. Complementation testing using the mutant lines ebr3 and ncr1 indicates that the ebr3 and ncr1 loci are nonallelic and recessive. ebr1 and ebr2 display no alterations in expression of the rice pathogenesis‐related (PR) genes PBZ1 and PR1, compared to wild‐type CO39. ebr3 has an elevated expression of PBZ1 and PR1 only in tissue displaying the LM phenotype. ncr1 strongly expresses PBZ1 in tissue displaying the LM phenotype, whereas PR1 expression in this tissue is similar to wild‐type CO39.
Telomere hypervariability in Magnaporthe oryzae
Authors: FARMAN MARK L. , KIM YUN‐SIK
Published: April 2010

The gray leaf spot disease of perennial ryegrass and tall fescue is caused by the fungus Magnaporthe oryzae (anamorph = Pyricularia oryzae). A collection of single‐copy and repetitive DNA markers was used to investigate genetic diversity among 22 isolates of the gray leaf spot pathogen. The single‐copy DNA markers revealed only three polymorphisms among 95 restriction fragments spanning ∼0.6% of the genome. In addition, Southern hybridization analysis and mating tests revealed that all isolates possessed the MAT1‐2 mating‐type allele. Fingerprinting of repetitive DNA loci using the Pot2 and MGR583 probes also revealed a high degree of genetic similarity (> 85%) among isolates. These data are consistent with the gray leaf spot pathogens having a recent evolutionary origin. In contrast to the results obtained with probes for internal chromosome loci, a telomere probe revealed that the chromosome ends of the very same isolates are highly divergent, with most isolates sharing less than 20% fingerprint similarity with any other isolate. Telomere mutations arise extremely frequently and changes in telomere fingerprint profiles were readily observed during vegetative growth and among cultures derived from single spores isolated from agar medium and from lesions on perennial ryegrass leaves.
Calorie restriction: what recent results suggest for the future of ageing research
Authors: Smith Daniel L. , Nagy Tim R. , Allison David B.
Published: April 2010

Eur J Clin Invest 2010; 40 (5): 440–450

Background Calorie Restriction (CR) research has expanded rapidly over the past few decades and CR remains the most highly reproducible, environmental intervention to improve health and extend lifespan in animal studies. Although many model organisms have consistently demonstrated positive responses to CR, it remains to be shown whether CR will extend lifespan in humans. Additionally, the current environment of excess caloric consumption and high incidence of overweight/obesity illustrate the improbable nature of the long‐term adoption of a CR lifestyle by a significant proportion of the human population. Thus, the search for substances that can reproduce the beneficial physiologic responses of CR without a requisite calorie intake reduction, termed CR mimetics (CRMs), has gained momentum.

Material and methods Recent articles describing health and lifespan results of CR in nonhuman primates and short‐term human studies are discussed. Additional consideration is given to the rapidly expanding search for CRMs.

Results The first results from a long‐term, randomized, controlled CR study in nonhuman primates showing statistically significant benefits on longevity have now been reported. Additionally, positive results from short‐term, randomized, controlled CR studies in humans are suggestive of potential health and longevity gains, while test of proposed CRMs (including rapamycin, resveratrol, 2‐deoxyglucose and metformin) have shown both positive and mixed results in rodents.

Conclusion Whether current positive results will translate into longevity gains for humans remains an open question. However, the apparent health benefits that have been observed with CR suggest that regardless of longevity gains, the promotion of healthy ageing and disease prevention may be attainable.
Effect of honey on gastric emptying of infants with protein energy malnutrition
Authors: Shaaban Sanaa Youssef , Abdulrhman Mamdouh Abdulmaksoud , Nassar May Fouad , Fathy Rasha Adel
Published: April 2010

Eur J Clin Invest 2010; 40 (5): 383–387

Background  Patients with protein‐energy malnutrition (PEM) have delayed gastric emptying time (GET) which may affect nutritional rehabilitation. This study was designed to examine the effect of honey on GET during nutritional rehabilitation of PEM patients.

Patients and methods  Thirty patients were enrolled and randomly assigned to one of two equal groups. One group received conventional nutritional rehabilitation therapy and the other received honey in addition. They were compared with 20 age‐ and sex‐matched controls. History taking, clinical examination and laboratory tests were performed for enrolled cases and GET was assessed using abdominal ultrasonography. These parameters were performed before and 2 weeks after nutritional rehabilitation.

Results  The GET was significantly delayed in the PEM groups compared with the controls. Further significant delay occurred in the honey supplemented group after nutritional rehabilitation, while the un‐supplemented group showed significant shortening of GET. The improvement of anthropometric measurements and laboratory parameters was equally noticed in the two PEM groups upon nutritional rehabilitation but their rate of change was distinctly higher, although non‐significant, in the group supplemented with honey.

Conclusion  Honey supplementation increased GET in PEM patients with positive effect on the improvement in the anthropometric measurements and serum albumin which makes us wonder that this delay in GET might be primarily a compensatory phenomenon and it was augmented by the use of honey. Larger scale studies with longer term follow up are recommended to further clear this point and assess any changes in the absorptive indices in honey supplemented PEM patients.
VEGF‐D△N△C mediated angiogenesis in skeletal muscles of diabetic WHHL rabbits
Authors: Roy Himadri , Bhardwaj Shalini , Babu Mohan , Lähteenvuo Johanna E. , Ylä‐Herttuala Seppo
Published: April 2010

Eur J Clin Invest 2010; 40 (5): 422–432

Background  Arterial occlusive disease is often associated with diabetes mellitus and hypercholesterolaemia which may reduce angiogenic potential of several growth factors. Accordingly, the usefulness of therapeutic angiogenesis in the presence of diabetes and hypercholesterolaemia has remained unclear. We evaluated angiogenic effects of the mature form of vascular endothelial growth factor‐D (VEGF‐D△N△C) in skeletal muscles in the presence of severe diabetes and hypercholesterolaemia.

Methods  Intra muscular injections of adenoviruses encoding human VEGF‐D△N△C (AdVEGF‐D△N△C) were given in the hind limbs of a group of diabetic hypercholesterolaemic rabbits and adenoviruses encoding LacZ (AdLacZ) were used as a control. All animals were killed 6 days after the gene transfer.

Results  Capillary count, capillary area, capillary permeability and perfusion were significantly higher in the AdVEGF‐D△N△C transduced muscles compared with the AdLacZ controls. Expressions of endothelial nitric oxide synthase (eNOS) and VEGF receptor(R)‐2 were also significantly increased in the VEGF‐D△N△C transduced muscles, along with an increased expression of angiopoietins (Angs) and neuropilin‐2 (NP‐2). Furthermore, VEGF‐D△N△C gene transfer to the skeletal muscles increased localized recruitment of cells with endothelial progenitor‐like characteristics.

Conclusions  VEGF‐D△N△C gene transfer can induce efficient angiogenesis in the presence of severe diabetes and hypercholesterolaemia by upregulating eNOS and VEGFR‐2 expression. VEGF‐D△N△C appears to be a promising agent for inducing therapeutic angiogenesis even in cases with severe diabetes and hypercholesterolaemia.
Influence of sediment organic enrichment and water alkalinity on growth of aquatic isoetid and elodeid plants
Authors: RAUN ANE LØVENDAHL , BORUM JENS , SAND‐JENSEN KAJ
Published: April 2010

1. Lake eutrophication has increased phytoplankton blooms and sediment organic matter. Among higher plants, small, oligotrophic rosette species (isoetids) have disappeared, while a few tall, eutrophic species (elodeids) may have persisted. Despite recent reduction of nutrient loading in restored lakes, the vegetation has rarely regained its former composition and coverage. Patterns of recovery may depend on local alkalinity because HCO3− stimulates photosynthesis of elodeids and not of isoetids. In laboratory growth experiments with two isoetids (Lobelia dortmanna and Littorella uniflora) and two elodeids (Potamogeton crispus and P. perfoliatus), we test whether organic enrichment of lake sediments has a long‐lasting influence by: (i) reducing plant growth because of oxygen stress on plant roots and (ii) inhibiting growth more for isoetids than elodeids. We also test whether (iii) increasing alkalinity (from 0.17 to 3.20 meq. L−1) enhances growth and reduces inhibition of organic sediment enrichment for elodeids but not for isoetids.

2. In low organic sediments, higher oxygen release from roots of isoetids than elodeids generated oxic conditions to greater sediment depth for Lobelia (4.3 cm) and Littorella (3.0 cm) than for Potamogeton species (1.6–2.2 cm). Sediment oxygen penetration depth fell rapidly to 0.4–1.0 cm for all four species at even modest organic enrichment and oxygen consumption in the sediments. Roots became shorter and isoetid roots became thicker to better supply oxygen to apical meristems.

3. Growth of elodeids was strongly inhibited across all levels of organic enrichment of sediments being eight‐fold lower at the highest enrichment compared to the unenriched control. Leaf biomass of isoetids increased three‐fold by moderate organic enrichment presumably because of greater CO2 supply from sediments being their main CO2 source. At higher organic enrichment, isoetid biomass was reduced, leaf chlorophyll declined up to 10‐fold, root length declined from 7 to <2 cm and mortality rose (up to 50%) signalling high plant stress.

4. Lobelia was not affected by HCO3− addition in accordance with its use of sediment CO2. Biomass of elodeids increased severalfold by rising alkalinity from 0.17 to 3.20 meq. L−1 in accordance with their use of HCO3− for photosynthesis, while the negative impact of organically enriched sediments remained.

5. Overall, root development of all four species was so strongly restricted in sediments enriched with labile organic matter that plants if growing in situ may lose root anchorage. Other experiments demonstrate that this risk is enhanced by greater water content and reduced consolidation in organically rich sediments. Therefore, formation of more muddy and oxygen‐demanding sediments during eutrophication will impede plant recovery in restored lakes while high local alkalinity will help elodeid recovery.
Inaccurate or disparate temperature cues? Seasonal acclimation of terrestrial and aquatic locomotor capacity in newts
Authors: Šamajová Pavlína , Gvoždík Lumír
Published: April 2010

1. Many organisms respond to seasonal temperature fluctuations by the reversible modification of whole‐animal performance. Semiaquatic ectotherms, which possess this acclimatory capacity in swimming speed, lack the plastic response in terrestrial locomotor performance and vice versa. Theory predicts that the presence of reversible (seasonal) thermal acclimation or fixed phenotypes depends on the predictability of future thermal conditions (i.e. accuracy of temperature cues) in a given environment. Alternatively, comparative data suggest that thermal acclimation is induced by disparate temperature cues in water and on land.

2. We tested both predictions by examining the seasonal acclimation response in thermal sensitivity of maximal swimming and running speed in adult alpine newts, Ichthyosaura (formerly Triturus) alpestris.

3. Following the seasonal variation in environmental temperatures, we exposed newts to 5 °C from November to March and, after a gradual temperature increase, to either a constant (15 °C) or fluctuating (10–20 °C) thermal regime from May to June. At the end of each treatment, we measured newt swimming and running capacity at five temperatures (range 5–25 °C). In the field, hourly temperatures were recorded in various aquatic and terrestrial microhabitats to obtain information about the predictability of thermal conditions in both environments.

4. Seasonal acclimation shaped the thermal sensitivity of swimming speed under both constant and fluctuating temperature treatments. Thermal sensitivity of running speed was markedly modified by a fluctuating thermal regime so that newts ran at the highest test temperature faster than cold‐acclimated individuals. Natural thermal environment contained a similar proportion of predictable variation in water and on land.

5. Complex seasonal acclimation of locomotor capacity in newts was influenced by the disparate thermal cues, i.e. mean acclimation temperature or diel temperature fluctuations, rather than by the different accuracy of these cues in water and on land. Future confrontations of theory with empirical data will require more attention not only on the assumptions of adaptive thermal acclimation but also on the ecologically relevant thermal conditions during acclimation experiments.
Male health status, signalled by courtship display, reveals ejaculate quality and hatching success in a lekking species
Authors: Chargé Rémi , Saint Jalme Michel , Lacroix Frédéric , Cadet Adeline , Sorci Gabriele
Published: April 2010

1. The information content of secondary sexual traits and the benefits gathered by choosy females are at the heart of sexual selection theory. Indicator models of sexual selection assume that secondary sexual traits reflect the phenotypic/genetic quality of their bearers and that females gather benefits from choosing these high‐quality males.

2. Here, we tested the idea that courtship display reflects the health status in a bird species with a lek‐based mating system, the houbara bustard (Chlamydotis undulata undulata). A group of males was treated with the lipopolysaccharide (LPS) of the cell wall of the bacterium Escherichia coli during the seasonal peak of courtship display, while another group of males was injected with a phosphate‐buffered saline solution (PBS) as a control. We then monitored the effect of the treatment on both courtship display and ejaculate quality. Finally, females were artificially inseminated with semen from LPS and PBS males, which allowed us to assess the effect of the immunological treatment on reproduction.

3. We found that the inflammatory challenge reduced courtship display and semen quality compared to controls. Interestingly, males that better resisted to the immune challenge in terms of courtship display also better resisted in terms of ejaculate quality. Early reproductive failure was increased when females were artificially inseminated with semen from immune‐activated males. Failure of eggs laid by females inseminated with LPS semen was due to a reduced fertilization power of sperm of LPS males or to increased embryo mortality in the very early stage of embryo development. As a consequence, hatching rate was reduced for females inseminated with semen collected from LPS males.

4. These results show that by assessing male courtship display, females may gain insight into the current phenotypic/genetic quality of mates and gather fitness benefits in terms of reproductive success.
New aspects on treatment modalities for thromboembolic episodes
Authors: Schulman S.
Published: April 2010

Abstract.  Schulman S (McMaster University, Hamilton, ON, Canada; and Karolinska University Hospital, Stockholm, Sweden). New aspects on treatment modalities for thromboembolic episodes (Review). J Intern Med 2010; 268: 109–119.

Venous thromboembolism (VTE) has been treated with a glycosaminoglycan, followed by a vitamin K antagonist during the past 60 years. During the past two decades the glycosaminoglycans have undergone refinement, allowing for simplification of care for these patients, but parenteral administration is still required. Therefore, the current completion of phase III trials with selective, predictable and orally available anticoagulants with rapid onset brings promise for a change in paradigm in the treatment of VTE in the next few years. Whereas these efforts will lead to further simplification of the therapy there are also trials conducted to advance the treatment by rapid resolution of the thromboembolism in order to improve long‐term outcome. Catheter‐directed thrombolysis, perhaps also with thrombus fragmentation and stent insertion, if demonstrated to be successful for the reduction of the postthrombotic syndrome, will only be an alternative for a minority of patients due to the complexity, risks and cost of therapy. This treatment increases the complexity at the same time as new drug regimens offer simplicity. This review focuses on the novel therapies for VTE although the new anticoagulants will also play a major role in the management of arterial disease, which will be briefly presented.
Synchronous infection with Mycobacterium chelonae and Paecilomyces in a heart transplant patient
Authors: Kim J.‐E. , Sung H. , Kim M.‐N. , Won C.‐H. , Chang S.‐E. , Lee M.‐W. , Choi J.‐H. , Moon K.‐C.
Published: April 2010

J.‐E. Kim, H. Sung, M.‐N. Kim, C.‐H. Won, S.‐E. Chang, M.‐W. Lee, J.‐H. Choi, K.‐C. Moon. Synchronous infection with Mycobacterium chelonae and Paecilomyces in a heart transplant patient. Transpl Infect Dis 2011: 13: 80–83. All rights reserved

Abstract: A 41‐year‐old male who was 3 years status post heart transplant presented with a 3‐month history of painful erythematous nodules and ulcers on his lower legs and right hand. First, Mycobacterium chelonae infection was revealed through several biopsies with molecular sequence analysis, and combination treatment, including clarithromycin, was started. During the treatment, lesions of the legs showed an improvement, but a fluctuant erythematous nodule on the thumb did not respond. Repetitive biopsy from the thumb ultimately identified Paecilomyces species and the patient was treated with itraconazole and terbinafine sequentially. Our case is the first report, to our knowledge, of synchronous infection with non‐tuberculous mycobacteria (NTM) and Paecilomyces in a solid organ transplant recipient. Our findings highlight the importance of recognizing cutaneous NTM infections or deep mycoses, as well as the importance of choosing an appropriate treatment.
Mapping resistance to the bird cherry‐oat aphid (Rhopalosiphum padi) in barley
Authors: Cheung W. Y. , Di Giorgio L. , Åhman I.
Published: April 2010

With 4 figures and 3 tables

Aphid resistance is a desirable trait in barley to combat the spread of the barley yellow dwarf virus and also to reduce the direct damage that aphids can inflict on cereals. A significant quantitative trait locus (QTL) on barley chromosome 3H was mapped based on a doubled‐haploid population derived from F1 of the cross ‘Lina’ × ‘5172‐28:4’ that showed segregation for resistance to bird cherry‐oat aphid. This QTL explained 9% of the variance in aphid growth and is a novel QTL for aphid resistance to bird cherry‐oat aphid. Combining this QTL on chromosome 3H with another major QTL on chromosome 2H would potentially provide a more durable and higher level of resistance. Depending on the prevalent species in the cultivated areas, pyramiding resistance to other aphid species such as the corn leaf aphid and the Russian wheat aphid will provide greater protection to the plant in the field against both aphids and barley yellow dwarf virus.