bluuebunny/crossref_metadata_2025 huggingface dataset:
Bacterial strategies for chemotaxis response
Authors: Celani Antonio , Vergassola Massimo
Published: January 2010

Regular environmental conditions allow for the evolution of specifically adapted responses, whereas complex environments usually lead to conflicting requirements upon the organism’s response. A relevant instance of these issues is bacterial chemotaxis, where the evolutionary and functional reasons for the experimentally observed response to chemoattractants remain a riddle. Sensing and motility requirements are in fact optimized by different responses, which strongly depend on the chemoattractant environmental profiles. It is not clear then how those conflicting requirements quantitatively combine and compromise in shaping the chemotaxis response. Here we show that the experimental bacterial response corresponds to the maximin strategy that ensures the highest minimum uptake of chemoattractants for
any
profile of concentration. We show that the maximin response is the unique one that always outcompetes motile but nonchemotactic bacteria. The maximin strategy is adapted to the variable environments experienced by bacteria, and we explicitly show its emergence in simulations of bacterial populations in a chemostat. Finally, we recast the contrast of evolution in regular vs. complex environments in terms of minimax vs. maximin game-theoretical strategies. Our results are generally relevant to biological optimization principles and provide a systematic possibility to get around the need to know precisely the statistics of environmental fluctuations.
Aromatic residues at the edge of the antibody combining site facilitate viral glycoprotein recognition through membrane interactions
Authors: Scherer Erin M. , Leaman Daniel P. , Zwick Michael B. , McMichael Andrew J. , Burton Dennis R.
Published: January 2010

The broadly neutralizing anti-HIV antibody 4E10 recognizes an epitope very close to the virus membrane on the glycoprotein gp41. It was previously shown that epitope recognition improves in a membrane context and that 4E10 binds directly, albeit weakly, to lipids. Furthermore, a crystal structure of Fab 4E10 complexed to an epitope peptide revealed that the centrally placed, protruding H3 loop of the antibody heavy chain does not form peptide contacts. To investigate the hypothesis that the H3 loop apex might interact with the viral membrane, two Trp residues in this region were substituted separately or in combination with either Ala or Asp by site-directed mutagenesis. The resultant IgG variants exhibited similar affinities for an epitope peptide as WT 4E10 but lower apparent affinities for both viral membrane mimetic liposomes and Env(−) virus. Variants also exhibited lower apparent affinities for Env(+) virions and failed to significantly neutralize a number of 4E10-sensitive viruses. For the extremely sensitive HXB2 virus, variants did neutralize, but at 37- to >250-fold lower titers than WT 4E10, with Asp substitutions exerting a greater effect on neutralization potency than Ala substitutions. Because reductions in lipid binding reflect trends in neutralization potency, we conclude that Trp residues in the antibody H3 loop enable membrane proximal epitope recognition through favorable lipid interactions. The requirement for lipophilic residues such as Trp adjacent to the antigen binding site may explain difficulties in eliciting 4E10-like neutralizing antibody responses by immunization and helps define a unique motif for antibody recognition of membrane proximal antigens.
Dual function of CTLA-4 in regulatory T cells and conventional T cells to prevent multiorgan autoimmunity
Authors: Jain Nitya , Nguyen Hai , Chambers Cynthia , Kang Joonsoo
Published: January 2010

Cytotoxic T lymphocyte antigen-4 (CTLA-4) is an inhibitory receptor on T cells essential for maintaining T cell homeostasis and tolerance to self. Mice lacking CTLA-4 develop an early onset, fatal breakdown in T cell tolerance. Whether this autoimmune disease occurs because of the loss of CTLA-4 function in regulatory T cells, conventional T cells, or both is unclear. We show here that lack of CTLA-4 in regulatory T cells leads to aberrant activation and expansion of conventional T cells. However, CTLA-4 expression in conventional T cells prevents aberrantly activated T cells from infiltrating and fatally damaging nonlymphoid tissues. These results demonstrate that CTLA-4 has a dual function in maintaining T cell tolerance: CTLA-4 in regulatory T cells inhibits inappropriate naïve T cell activation and CTLA-4 in conventional T cells prevents the harmful accumulation of self-reactive pathogenic T cells in vital organs.
Leveraging skewed transcript abundance by RNA-Seq to increase the genomic depth of the tree of life
Authors: Hittinger Chris Todd , Johnston Mark , Tossberg John T. , Rokas Antonis
Published: January 2010

Assembling the tree of life is a major goal of biology, but progress has been hindered by the difficulty and expense of obtaining the orthologous DNA required for accurate and fully resolved phylogenies. Next-generation DNA sequencing technologies promise to accelerate progress, but sequencing the genomes of hundreds of thousands of eukaryotic species remains impractical. Eukaryotic transcriptomes, which are smaller than genomes and biased toward highly expressed genes that tend to be conserved, could potentially provide a rich set of phylogenetic characters. We sampled the transcriptomes of 10 mosquito species by assembling 36-bp sequence reads into phylogenomic data matrices containing hundreds of thousands of orthologous nucleotides from hundreds of genes. Analysis of these data matrices yielded robust phylogenetic inferences, even with data matrices constructed from surprisingly few sequence reads. This approach is more efficient, data-rich, and economical than traditional PCR-based and EST-based methods and provides a scalable strategy for generating phylogenomic data matrices to infer the branches and twigs of the tree of life.
Anthrax toxin triggers the activation of
src
-like kinases to mediate its own uptake
Authors: Abrami Laurence , Kunz Béatrice , Gisou van der Goot F.
Published: January 2010

AB-type toxins, like other bacterial toxins, are notably opportunistic molecules. They rely on target cell receptors to reach the appropriate location within the target cell where translocation of their enzymatic subunits occurs. The anthrax toxin, however, times its own uptake, suggesting that toxin binding triggers specific signaling events. Here we show that the anthrax toxin triggers tyrosine phosphorylation of its own receptors, capillary morphogenesis gene 2 and tumor endothelial marker 8, which are not endowed with intrinsic kinase activity. This is required for efficient toxin uptake because endocytosis of the mutant receptor lacking the cytoplasmic tyrosine residues is strongly delayed. Phosphorylation of the receptors was dependent on
src
-like kinases, which where activated upon toxin binding. Importantly,
src
-dependent phosphorylation of the receptor was required for its subsequent ubiquitination, which in turn was required for clathrin-mediated endocytosis. Consistently, we found that uptake of the anthrax toxin and processing of the lethal factor substrate MEK1 are inhibited by silencing of
src
and
fyn
, as well as in
src
and
fyn
knockout cells.
Virus discovery by deep sequencing and assembly of virus-derived small silencing RNAs
Authors: Wu Qingfa , Luo Yingjun , Lu Rui , Lau Nelson , Lai Eric C. , Li Wan-Xiang , Ding Shou-Wei
Published: January 2010

In response to infection, invertebrates process replicating viral RNA genomes into siRNAs of discrete sizes to guide virus clearance by RNA interference. Here, we show that viral siRNAs sequenced from fruit fly, mosquito, and nematode cells were all overlapping in sequence, suggesting a possibility of using siRNAs for viral genome assembly and virus discovery. To test this idea, we examined contigs assembled from published small RNA libraries and discovered five previously undescribed viruses from cultured Drosophila cells and adult mosquitoes, including three with a positive-strand RNA genome and two with a dsRNA genome. Notably, four of the identified viruses exhibited only low sequence similarities to known viruses, such that none could be assigned into an existing virus genus. We also report detection of virus-derived PIWI-interacting RNAs (piRNAs) in
Drosophila melanogaster
that have not been previously described in any other host species and demonstrate viral genome assembly from viral piRNAs in the absence of viral siRNAs. Thus, this study provides a powerful culture-independent approach for virus discovery in invertebrates by assembling viral genomes directly from host immune response products without prior virus enrichment or amplification. We propose that invertebrate viruses discovered by this approach may include previously undescribed human and vertebrate viral pathogens that are transmitted by arthropod vectors.
Hippo signaling is a potent in vivo growth and tumor suppressor pathway in the mammalian liver
Authors: Lu Li , Li Ying , Kim Soo Mi , Bossuyt Wouter , Liu Pu , Qiu Qiong , Wang Yingdi , Halder Georg , Finegold Milton J. , Lee Ju-Seog , Johnson Randy L.
Published: January 2010

How organ size is controlled in mammals is not currently understood. In
Drosophila
the Hippo signaling pathway functions to suppress growth in imaginal discs and has been suggested to control organ size. To investigate the role of hippo signaling in regulation of mammalian organ size we have generated conditional alleles of
Sav1
,
mst1
, and
mst2
, orthologs of Drosophila
Salvador
and
hippo
, respectively. Specific deletion of both
mst1
and
mst2
in hepatocytes results in significantly enlarged livers due to excessive proliferation. By the age of 5–6 months,
mst1/2
conditional mutant livers have multiple foci of liver tumors, indicating that the combined activities of
mst1
and
mst2
act as redundant tumor suppressors in hepatocytes. Similar findings were obtained with liver-specific deletion of
Sav1
, a second core Hippo signaling component that facilitates activation of
mst1
and
mst2
. Tumors from
sav1
mutants exhibited varied morphology, suggesting a mixed-lineage origin of tumor-initiating cells. Transcriptional profiling of liver tissues from both
mst1/2
and
sav1
conditional mutants revealed a network of Hippo signaling regulated genes with specific enrichment for genes involved in immune and inflammatory responses. Histological and immunological characterization of
mst1/2
double mutant liver tissues revealed abundant accumulation of adult facultative stem cells termed oval cells in periductal regions. Because oval cells induction is commonly associated with liver injury and tumor formation, it is likely that these cells contribute to the enlarged livers and hepatomas that we observe in
sav1
and
mst1/2
mutants. Taken together, our results demonstrate that the Hippo signaling pathway is a critical regulator of mammalian liver growth and a potent suppressor of liver tumor formation.
Ubiquitin carboxyl-terminal hydrolase L1 is required for maintaining the structure and function of the neuromuscular junction
Authors: Chen Fujun , Sugiura Yoshie , Myers Kalisa Galina , Liu Yun , Lin Weichun
Published: January 2010

The enzyme ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1) is one of the most abundant proteins in the mammalian nervous system. In humans, UCH-L1 is also found in the ubiquitinated inclusion bodies that characterize neurodegenerative diseases in the brain, suggesting its involvement in neurodegeneration. The physiologic role of UCH-L1 in neurons, however, remains to be further elucidated. For example, previous studies have provided evidence both for and against the role of UCH-L1 in synaptic function in the brain. Here, we have characterized a line of knockout mice deficient in the
UCH-L1
gene. We found that, in the absence of UCH-L1, synaptic transmission at the neuromuscular junctions (NMJs) is markedly impaired. Both spontaneous and evoked synaptic activity are reduced; paired pulse-facilitation is impaired, and synaptic transmission fails to respond to high-frequency, repetitive stimulation at the NMJs of
UCH-L1
knockout mice. Morphologic analyses of the NMJs further revealed profound structural defects—loss of synaptic vesicles and accumulation of tubulovesicular structures at the presynaptic nerve terminals, and denervation of the muscles in
UCH-L1
knockout mice. These findings demonstrate that UCH-L1 is required for the maintenance of the structure and function of the NMJ and that the loss of normal UCH-L1 activity may result in neurodegeneration in the peripheral nervous system.
Decreased necrotizing fasciitis capacity caused by a single nucleotide mutation that alters a multiple gene virulence axis
Authors: Olsen Randall J. , Sitkiewicz Izabela , Ayeras Ara A. , Gonulal Vedia E. , Cantu Concepcion , Beres Stephen B. , Green Nicole M. , Lei Benfang , Humbird Tammy , Greaver Jamieson , Chang Ellen , Ragasa Willie P. , Montgomery Charles A. , Cartwright Joiner , McGeer Allison , Low Donald E. , Whitney Adeline R. , Cagle Philip T. , Blasdel Terry L. , DeLeo Frank R. , Musser James M.
Published: January 2010

Single-nucleotide changes are the most common cause of natural genetic variation among members of the same species, but there is remarkably little information bearing on how they alter bacterial virulence. We recently discovered a single-nucleotide mutation in the group A
Streptococcus
genome that is epidemiologically associated with decreased human necrotizing fasciitis (“flesh-eating disease”). Working from this clinical observation, we find that wild-type
mtsR
function is required for group A
Streptococcus
to cause necrotizing fasciitis in mice and nonhuman primates. Expression microarray analysis revealed that
mtsR
inactivation results in overexpression of PrsA, a chaperonin involved in posttranslational maturation of SpeB, an extracellular cysteine protease. Isogenic mutant strains that overexpress
prsA
or lack
speB
had decreased secreted protease activity in vivo and recapitulated the necrotizing fasciitis-negative phenotype of the Δ
mtsR
mutant strain in mice and monkeys.
mtsR
inactivation results in increased PrsA expression, which in turn causes decreased SpeB secreted protease activity and reduced necrotizing fasciitis capacity. Thus, a naturally occurring single-nucleotide mutation dramatically alters virulence by dysregulating a multiple gene virulence axis. Our discovery has broad implications for the confluence of population genomics and molecular pathogenesis research.
Vesicular stomatitis virus oncolysis is potentiated by impairing mTORC1-dependent type I IFN production
Authors: Alain Tommy , Lun XueQing , Martineau Yvan , Sean Polen , Pulendran Bali , Petroulakis Emmanuel , Zemp Franz J. , Lemay Chantal G. , Roy Dominic , Bell John C. , Thomas George , Kozma Sara C. , Forsyth Peter A. , Costa-Mattioli Mauro , Sonenberg Nahum
Published: January 2010

Oncolytic viruses constitute a promising therapy against malignant gliomas (MGs). However, virus-induced type I IFN greatly limits its clinical application. The kinase mammalian target of rapamycin (mTOR) stimulates type I IFN production via phosphorylation of its effector proteins, 4E-BPs and S6Ks. Here we show that mouse embryonic fibroblasts and mice lacking S6K1 and S6K2 are more susceptible to vesicular stomatitis virus (VSV) infection than their WT counterparts as a result of an impaired type I IFN response. We used this knowledge to employ a pharmacoviral approach to treat MGs. The highly specific inhibitor of mTOR rapamycin, in combination with an IFN-sensitive VSV-mutant strain (VSV
ΔM51
), dramatically increased the survival of immunocompetent rats bearing MGs. More importantly, VSV
ΔM51
selectively killed tumor, but not normal cells, in MG-bearing rats treated with rapamycin. These results demonstrate that reducing type I IFNs through inhibition of mTORC1 is an effective strategy to augment the therapeutic activity of VSV
ΔM51
.
Histone acetyltransferase Rtt109 is required forCandida albicanspathogenesis
Authors: Lopes da Rosa Jessica , Boyartchuk Victor L. , Zhu Lihua Julie , Kaufman Paul D.
Published: January 2010

Candida albicansis a ubiquitous opportunistic pathogen that is the most prevalent cause of hospital-acquired fungal infections. In mammalian hosts,C. albicansis engulfed by phagocytes that attack the pathogen with DNA-damaging reactive oxygen species (ROS). Acetylation of histone H3 lysine 56 (H3K56) by the fungal-specific histone acetyltransferase Rtt109 is important for yeast model organisms to survive DNA damage and maintain genome integrity. To assess the importance of Rtt109 forC. albicanspathogenicity, we deleted the predicted homolog of Rtt109 in the clinicalC. albicansisolate, SC5314.C. albicans rtt109−/−mutant cells lack acetylated H3K56 (H3K56ac) and are hypersensitive to genotoxic agents. Additionally,rtt109−/−mutant cells constitutively display increased H2A S129 phosphorylation and elevated DNA repair gene expression, consistent with endogenous DNA damage. Importantly,C. albicans rtt109−/−cells are significantly less pathogenic in mice and more susceptible to killing by macrophages in vitro than are wild-type cells. Via pharmacological inhibition of the host NADPH oxidase enzyme, we show that the increased sensitivity ofrtt109−/−cells to macrophages depends on the host’s ability to generate ROS, providing a mechanistic link between the drug sensitivity, gene expression, and pathogenesis phenotypes. We conclude that Rtt109 is particularly important for fungal pathogenicity, suggesting a unique target for therapeutic antifungal compounds.
Lack of evolvability in self-sustaining autocatalytic networks constraints metabolism-first scenarios for the origin of life
Authors: Vasas Vera , Szathmáry Eörs , Santos Mauro
Published: January 2010

A basic property of life is its capacity to experience Darwinian evolution. The replicator concept is at the core of genetics-first theories of the origin of life, which suggest that self-replicating oligonucleotides or their similar ancestors may have been the first “living” systems and may have led to the evolution of an RNA world. But problems with the nonenzymatic synthesis of biopolymers and the origin of template replication have spurred the alternative metabolism-first scenario, where self-reproducing and evolving proto-metabolic networks are assumed to have predated self-replicating genes. Recent theoretical work shows that “compositional genomes” (i.e., the counts of different molecular species in an assembly) are able to propagate compositional information and can provide a setup on which natural selection acts. Accordingly, if we stick to the notion of replicator as an entity that passes on its structure largely intact in successive replications, those macromolecular aggregates could be dubbed “ensemble replicators” (composomes) and quite different from the more familiar genes and memes. In sharp contrast with template-dependent replication dynamics, we demonstrate here that replication of compositional information is so inaccurate that fitter compositional genomes cannot be maintained by selection and, therefore, the system lacks evolvability (i.e., it cannot substantially depart from the asymptotic steady-state solution already built-in in the dynamical equations). We conclude that this fundamental limitation of ensemble replicators cautions against metabolism-first theories of the origin of life, although ancient metabolic systems could have provided a stable habitat within which polymer replicators later evolved.
Quorum-regulated biofilms enhance the development of conditionally viable, environmental
Vibrio cholerae
Authors: Kamruzzaman M. , Udden S. M. Nashir , Cameron D. Ewen , Calderwood Stephen B. , Nair G. Balakrish , Mekalanos John J. , Faruque Shah M.
Published: January 2010

The factors that enhance the waterborne spread of bacterial epidemics and sustain the pathogens in nature are unclear. The epidemic diarrheal disease cholera caused by
Vibrio cholerae
spreads through water contaminated with the pathogen. However, the bacteria exist in water mostly as clumps of cells, which resist cultivation by standard techniques but revive into fully virulent form in the intestinal milieu. These conditionally viable environmental cells (CVEC), alternatively called viable but nonculturable cells, presumably play a crucial role in cholera epidemiology. However, the precise mechanism causing the transition of
V. cholerae
to the CVEC form and this form's significance in the biology of the pathogen are unknown. Here we show that this process involves biofilm formation that is dependent on quorum sensing, a regulatory response that is controlled by cell density.
V. cholerae
strains carrying mutations in genes required for quorum sensing and biofilm formation displayed altered CVEC formation in environmental water following intestinal infections. Analysis of naturally occurring
V. cholerae
CVEC showed that organisms that adopt this quiescent physiological state typically exist as clumps of cells that comprise a single clone closely related to isolates causing the most recent local cholera epidemic. These results support a model of cholera transmission in which in vivo-formed biofilms convert to CVEC upon the introduction of cholera stools into environmental water. Our data further suggest that a temporary loss of quorum sensing due to dilution of extracellular autoinducers confers a selective advantage to communities of
V. cholerae
by blocking quorum-mediated regulatory responses that would break down biofilms and thus interfere with CVEC formation.
Evolutionary diversification, coevolution between populations and their antagonists, and the filling of niche space
Authors: Ricklefs Robert E.
Published: January 2010

The population component of a species’ niche corresponds to the distribution of individuals across environments within a region. As evolutionary clades of species diversify, they presumably fill niche space, and, consequently, the rate of increase in species numbers slows. Total niche space and species numbers appear to be relatively stable over long periods, and so an increase in the species richness of one clade must be balanced by decrease in others. However, in several analyses, the total population niche space occupied per clade is independent of the number of species, suggesting that species in more diverse clades overlap more in niche space. This overlap appears to be accommodated by variation in the populations of each species, including their absence, within suitable niche space. I suggest that the uneven filling of niche space results from localized outcomes of the dynamic coevolutionary interactions of populations with their pathogens or other antagonists. Furthermore, I speculate that relationships with pathogens might constrain diversification if pathogen diversity increased with host diversity and resulted in more frequent host switching and emergent disease. Many indirect observations are consistent with these scenarios. However, the postulated influence of pathogens on the filling of niche space and diversification of clades primarily highlights our lack of knowledge concerning the space and time dimensions of coevolutionary interactions and their influence on population distribution and species diversification.
Potential on-shore and off-shore reservoirs for CO
2
sequestration in Central Atlantic magmatic province basalts
Authors: Goldberg David S. , Kent Dennis V. , Olsen Paul E.
Published: January 2010

Identifying locations for secure sequestration of CO
2
in geological formations is one of our most pressing global scientific problems. Injection into basalt formations provides unique and significant advantages over other potential geological storage options, including large potential storage volumes and permanent fixation of carbon by mineralization. The Central Atlantic Magmatic Province basalt flows along the eastern seaboard of the United States may provide large and secure storage reservoirs both onshore and offshore. Sites in the South Georgia basin, the New York Bight basin, and the Sandy Hook basin offer promising basalt-hosted reservoirs with considerable potential for CO
2
sequestration due to their proximity to major metropolitan centers, and thus to large industrial sources for CO
2
. Onshore sites are suggested for cost-effective characterization studies of these reservoirs, although offshore sites may offer larger potential capacity and additional long-term advantages for safe and secure CO
2
sequestration.
The integrin reconstruction act
Authors: Short Ben
Published: January 2010

Recreating integrin activation in vitro resolves several long-running controversies.
jORCA: easily integrating bioinformatics Web Services
Authors: Martín-Requena Victoria , Ríos Javier , García Maximiliano , Ramírez Sergio , Trelles Oswaldo
Published: January 2010

Motivation: Web services technology is becoming the option of choice to deploy bioinformatics tools that are universally available. One of the major strengths of this approach is that it supports machine-to-machine interoperability over a network. However, a weakness of this approach is that various Web Services differ in their definition and invocation protocols, as well as their communication and data formats—and this presents a barrier to service interoperability.

Results: jORCA is a desktop client aimed at facilitating seamless integration of Web Services. It does so by making a uniform representation of the different web resources, supporting scalable service discovery, and automatic composition of workflows. Usability is at the top of the jORCA agenda; thus it is a highly customizable and extensible application that accommodates a broad range of user skills featuring double-click invocation of services in conjunction with advanced execution-control, on the fly data standardization, extensibility of viewer plug-ins, drag-and-drop editing capabilities, plus a file-based browsing style and organization of favourite tools. The integration of bioinformatics Web Services is made easier to support a wider range of users.

Availability and Implementation: jORCA binaries and extended documentation are freely available at http://www.bitlab-es.com/jorca under the Creative Commons Attribution-No Derivative Works 2.5 Spain License and jORCA source code (implemented in Java) is available under request. (GPL v3 license). jORCA has been tested under UNIX (Fedora 11, open SUSE 11 and Ubuntu 8.1), MS-Windows and Mac OS 10.5 operating systems. Java VM version 1.6.0 later is required.

Contact:  ots@uma.es or vickymr@uma.es

Supplementary information:  Supplementary data are available at Bioinformatics online.
Recognition memory and the hippocampus: A test of the hippocampal contribution to recollection and familiarity
Authors: Jeneson Annette , Kirwan C. Brock , Hopkins Ramona O. , Wixted John T. , Squire Larry R.
Published: January 2010

It has been suggested that the hippocampus selectively supports recollection and that adjacent cortex in the medial temporal lobe can support familiarity. Alternatively, it has been suggested that the hippocampus supports both recollection and familiarity. We tested these suggestions by assessing the performance of patients with hippocampal lesions on recognition memory tests that differ in the extent to which recollection and familiarity contribute to the recognition decision. When targets and foils are highly similar, prior evidence suggests that, on a forced-choice test in which targets are presented together with highly similar, corresponding foils (the FC-C format), performance is supported primarily by familiarity. By contrast, when targets are presented together with foils that are similar to other targets (the FC-NC format) or when memory is tested in a yes/no (Y/N) format, performance is based much more strongly on recollection. Accordingly, a finding that hippocampal damage impaired both Y/N recognition and FC-NC recognition but spared FC-C recognition would suggest that the hippocampus selectively supports recollection. We administered Y/N, FC-C, and FC-NC tests to five memory-impaired patients with circumscribed hippocampal lesions and 14 controls. The patients were impaired on all three types of recognition test, and there was no indication that the patients were disproportionately benefited or disproportionately impaired on any test. This pattern of performance suggests that the hippocampus supports both recollection and familiarity.
Ab initiostructure solution by iterative phase-retrieval methods: performance tests on charge flipping and low-density elimination
Authors: Fleischer Frank , Weber Thomas , Deloudi Sofia , Palatinus Lukáš , Steurer Walter
Published: January 2010

Comprehensive tests on the density-modification methods charge flipping [Oszlányi & Sütő (2004).Acta Cryst.A60, 134–141] and low-density elimination [Shiono & Woolfson (1992).Acta Cryst.A48, 451–456] for solving crystal structures are performed on simulated diffraction data of periodic structures and quasicrystals. A novel model-independent figure of merit, which characterizes the reliability of the retrieved phase of each reflection, is introduced and tested. The results of the performance tests show that the quality of the phase retrieval highly depends on the presence or absence of an inversion center and on the algorithm used for solving the structure. Charge flipping has a higher success rate for solving structures, while low-density elimination leads to a higher accuracy in phase retrieval. The best results can be obtained by combining the two methods,i.e.by solving a structure with charge flipping followed by a few cycles of low-density elimination. It is shown that these additional cycles dramatically improve the phases not only of the weak reflections but also of the strong ones. The results can be improved further by averaging the results of several runs and by applying a correction term that compensates for a reduction of the structure-factor amplitudes by averaging of inconsistently observed reflections. It is further shown that in most cases the retrieved phases converge to the best solution obtainable with a given method.
Enhancement of SHG efficiency by urea doping in ZTS single crystals and its correlation with crystalline perfection as revealed by Kurtz powder and high-resolution X-ray diffraction methods
Authors: Bhagavannarayana G. , Kushwaha S. K.
Published: January 2010

The enhancement of second-harmonic generation (SHG) efficiency by urea doping in tristhioureazinc(II) sulfate (ZTS) single crystals and its correlation with crystalline perfection have been investigated. ZTS is a potential semiorganic nonlinear optical material. Pure and urea-doped single crystals of ZTS have been successfully grown by the slow evaporation solution technique. The presence of dopant has been confirmed and analysed by Fourier transform infrared spectrometry. The influence of urea doping at different concentrations on crystalline perfection has been thoroughly assessed by high-resolution X-ray diffractometry (HRXRD). HRXRD studies revealed that the ZTS crystals could accommodate urea up to a critical concentration without any deterioration in crystalline perfection. Above this concentration, very low angle structural grain boundaries developed and it seems the excess urea above the critical concentration was segregated along the grain boundaries. At very high doping concentrations, the crystals were found to contain mosaic blocks. The SHG efficiency has been studied using the Kurtz powder technique. The relative SHG efficiency of the crystals was found to increase substantially with the increase in urea concentration. The correlation found between crystalline perfection and SHG efficiency is discussed.
Revised phase diagram for the Nd–Pt system from 35 to 85 at% platinum
Authors: Xu Ch. F. , Gu Z. F. , Cheng G. , Zhou H. Y. , Wang Z. M. , Liu X. M. , Han Q. Y. , Jiang M. H.
Published: January 2010

The phase diagram of the Nd–Pt system from 35 to 85 at%Pt has been revised using X-ray diffraction and differential thermal analysis. It is found that the Nd3Pt4phase with the rhombohedral Pd4Pu3structure type is unstable and decomposes into the two neighboring phases NdPt and NdPt2at temperatures ranging approximately from 583 to 1123 K. It is confirmed that the homogeneity range for the Laves phase NdPt2extends from about 68.5 to 75.3 at%Pt in the Nd–Pt binary system. The polymorphic transformation temperature of α-NdPt ⇌ β-NdPt is about 623 K, where the α-NdPt phase with BFe type is stable at low temperatures and the β-NdPt phase with BCr type at high temperatures.
Refinement of the λ/2 contribution to CCD detector data
Authors: Dudka Alexander
Published: January 2010

A new method is proposed to improve structure modeling by taking into account the half-wavelength contribution (λ/2) to X-ray data measured on CCD and image-plate diffractometers. Such an effect arises because the reflection intensities contain contributions associated with both the λ and the λ/2 wavelengths. The ratiowof these two contributions is a new parameter refined using the full-matrix least-squares techniques. The new method does not require any additional measurement or information. According to the tests performed, proper account of the λ/2 contribution lowers thewR2(|F|2) factors by a relative percent difference of 4–14% and the atomic displacement parameters by ∼1–4 s.u. Other effects are analyzed that might correlate with the λ/2 contribution, such as absorption, charge-density redistribution, thermal diffuse scattering and extinction. Strong correlation was found betweenwand the other parameters, but a fixed λ/2 correction reduces this difficulty. The value ofwis found to be both characteristic of the diffractometer and a general indicator of the refinement quality (similar toRfactors).
The use of novel organic gels and hydrogels in protein crystallization
Authors: Pietras Zbigniew , Lin Hong-Ting , Surade Sachin , Luisi Ben , Slattery Orla , Pos Klaas M. , Moreno Abel
Published: January 2010

The use of an organic solvent-based gel prepared from polyethylene oxide and a polyvinyl alcohol hydrogel for protein crystallization was investigated. The preparation, properties and application of the gels for protein crystallization are described, and the advantages and limitations of the approach are discussed. The gels are compared with agar, which is a popular aqueous gel used for protein crystallization. The growth behaviour and diffraction quality of crystals prepared in these gel media were evaluated for two model soluble proteins, thaumatin and lysozyme, and for two bacterial membrane proteins, TolC and AcrB.
Sequential expression of macrophage anti-microbial/inflammatory and wound healing markers following innate, alternative and classical activation
Authors: Menzies F M , Henriquez F L , Alexander J , Roberts C W
Published: January 2010

The present study examines the temporal dynamics of macrophage activation marker expression in response to variations in stimulation. We demonstrate that markers can be categorized as ‘early’ (expressed most abundantly at 6 h post-stimulation) or ‘late’ (expressed at 24 h post-stimulation). Thus nos2 and p40 (IL-12/IL-23) are early markers of innate and classical activation, while dectin-1 and mrc-1 are early markers and fizz1 (found in inflammatory zone-1) and ym1 are late markers of alternative activation. Furthermore, argI is a late marker of both innate and alternative activation. The ability of interferon (IFN)-γ to alter these activation markers was studied at both the protein level and gene level. As reported previously, IFN-γ was able to drive macrophages towards the classical phenotype by enhancing nos2 gene expression and enzyme activity and p40 (IL-12/IL-23) gene expression in lipopolysaccharide (LPS)-stimulated macrophages. IFN-γ antagonized alternative macrophage activation, as evident by reduced expression of dectin-1, mrc-1, fizz1 and ym1 mRNA transcripts. In addition, IFN-γ antagonized arginase activity irrespective of whether macrophages were activated innately or alternatively. Our data explain some apparent contradictions in the literature, demonstrate temporal plasticity in macrophage activation states and define for the first time ‘early’ and ‘late’ markers associated with anti-microbial/inflammatory and wound healing responses, respectively.
El Niño Southern Oscillation and climate trends impact reservoir water quality
Authors: MARCÉ RAFAEL , RODRÍGUEZ‐ARIAS MIQUEL ÀNGEL , GARCÍA JUAN CARLOS , ARMENGOL JOAN
Published: January 2010

Low dissolved oxygen concentration in bottom layers of lakes and reservoirs usually indicates low water quality. In lakes, empirical models predicting anoxia are almost entirely based on the decay of plankton biomass, while in reservoirs recent findings suggest a prominent role of streamflow and load of organic carbon. This suggests a potential link between water quality in reservoirs and climate processes affecting streamflow. Here we support this hypothesis presenting evidence that both interannual climate variability and recent climate change, mainly consisting in a significant increase in potential evapotranspiration in the upstream basin, affected the oxygen content in a Mediterranean reservoir (Sau Reservoir, Spain). Using a 44‐year monthly record, we found strong and consistent signatures of El Niño Southern Oscillation in the inflow and reservoir oxygen content. Spectral and wavelet techniques showed that the El Niño, streamflow, and reservoir oxygen content series oscillated in common periods, which coincided with the main El Niño variability modes. An empirical model explaining the annual oxygen content in the reservoir suggested that a decreasing streamflow trend reduced the oxygen content of the reservoir by about 20%, counteracting remediation measures implemented at the basin upstream the reservoir. Our results provide the first quantitative evidence of climate change effects on reservoir water quality using long‐term instrumental data, and indicate that streamflow should be considered as a key variable in assessing climate change impact on reservoir water quality. These results are especially relevant in regions of the world where reservoirs are abundant and most climate models predict a decrease in runoff during the next decades. Both the expected trends and the sensitivity of reservoir water quality to global interannual climate variability should be considered for a correct management of water resources in the present and to design adaptation policies in the future.
Reproductive competition favours solitary living while ecological constraints impose group‐living in African striped mice
Authors: Schradin Carsten , König Barbara , Pillay Neville
Published: January 2010

1.Social groups typically form due to delayed dispersal of adult offspring when no opportunities for independent breeding exist, or the costs of dispersal are higher than the costs of remaining philopatric. Ecological constraints are thought to be a main reason for group‐living in animals.

2.Reproductive competition within groups can induce high costs of philopatry, and is thought to be a main reason for solitary living.

3.Experimental manipulation of reproductive competition is difficult. One solution is to compare sociality between periods with and without reproductive competition.

4.Here, we show empirically in a 8‐year field study that striped mice (Rhabdomys pumilio) of both sexes were group‐living during the breeding season when population density (PD) was high but solitary living when PD was low, supporting the ecological constraints model.

5.After the breeding season, in the absence of reproductive competition, the positive correlation between PD and percentage of group‐living striped mice was absent. Almost all striped mice were group‐living even under very low population densities. This supports the reproductive competition model.

6.Ambient temperature, food availability and predation pressure, did not influence sociality.

7.In captivity, the costs of reproductive competition in communal groups include female infanticide and aggression between females.

8.We conclude that group‐living is favoured by constraints imposed through habitat saturation and by its benefits (improved thermoregulation by huddling, group‐territoriality and predator avoidance), and that reproductive competition is a major force favouring solitary living in striped mice.
Adenovirus‐Mediated Leptin Expression Normalises Hypertension Associated with Diet‐Induced Obesity
Authors: Zhang W. , Telemaque S. , Augustyniak R. A. , Anderson P. , Thomas G. D. , An J. , Wang Z. , Newgard C. B. , Victor R. G.
Published: January 2010

In our previous study, moderate increases in plasma leptin levels achieved via administration of recombinant adenovirus containing the rat leptin cDNA were shown to correct the abnormal metabolic profile in rats with diet‐induced obesity, suggesting that these animals had developed resistance to the metabolic effects of leptin, which could be reversed by leptin gene over‐expression. However, the effect of this therapeutic strategy on blood pressure was not investigated. The present study aimed to determine whether a moderate increase of endogenous plasma leptin levels affected arterial blood pressure in rats with diet‐induced obesity and hypertension. The major finding from the present study was that the natural rise in plasma leptin with weight‐gain is insufficient to counterbalance high blood pressure associated with obesity, additional increases of circulating leptin levels with adenoviral leptin gene therapy led to normalisation of blood pressure in high‐fat diet‐induced obese and hypertensive rats. Mechanistically, the reduction of blood pressure by leptin in obese rats was likely independent of α‐adrenergic and acetylcholinergic receptor mediation. This is the first study to demonstrate that further increases in circulating leptin levels by leptin gene transfer during obesity could reduce blood pressure.
De novo duplication of MECP2 in a girl with mental retardation and no obvious dysmorphic features
Authors: Makrythanasis P , Moix I , Gimelli S , Fluss J , Aliferis K , Antonarakis SE , Morris MA , Béna F , Bottani A
Published: January 2010

Makrythanasis P, Moix I, Gimelli S, Fluss J, Aliferis K, Antonarakis SE, Morris MA, Béna F, Bottani A. De novo duplication of MECP2 in a girl with mental retardation and no obvious dysmorphic features.

Loss‐of‐function mutations of MECP2 are responsible for Rett syndrome (RTT), an X‐linked neurodevelopmental disorder affecting mainly girls. The availability of MECP2 testing has led to the identification of such mutations in girls with atypical RTT features and the recognition of milder forms. Furthermore, duplication of the entire gene has recently been described in boys with mental retardation and recurrent infections. We describe a girl with a heterozygous de novo MECP2 duplication. The patient, at the age of 19, has mental retardation with no autistic features. She is friendly but gets frequently anxious. She has neither dysmorphic features nor malformations. Her motor development was delayed with walking at 20 months. Speech is fluid with good pronunciation but is simple and repetitive. Diagnosis was made after single‐strand conformation analysis (SSCA) and multiplex ligation‐dependent probe amplification (MLPA) analysis of MECP2. Array comparative genomic hybridization (aCGH) analysis showed a duplication of 29 kb including MECP2 and part of IRAK1. Fluorescent in situ hybridization (FISH) has revealed that the duplicated region is inserted near the telomere of the short arm of chromosome 10. X‐chromosome inactivation in leukocyte DNA was not skewed. We conclude that it is likely that this MECP2 duplication is responsible for the mental retardation in this patient. This case broadens the phenotypic spectrum of MECP2 abnormalities with consequent implication in diagnosis and genetic counselling of girls with non‐syndromic mental retardation.
The management of splenic artery aneurysm in patients awaiting liver transplantation
Authors: Asthana S. , Toso C. , McCarthy M. , Shapiro A.M.J.
Published: January 2010

Asthana S, Toso C, McCarthy M, Shapiro AMJ. The management of splenic artery aneurysm in patients awaiting liver transplantation. Clin Transplant 2010 DOI: 10.1111/j.1399‐0012.2009.01192.x © 2010 John Wiley & Sons A/S.

Abstract:  Splenic artery aneurysms (SAAs) are the third most common forms of intra‐abdominal aneurysm, and the most commonly encountered visceral aneurysms in the general population. SAAs occur more commonly in patients with portal hypertension and liver failure and, as such, are often encountered in patients undergoing high‐resolution abdominal imaging as part of a work‐up for liver transplantation. While rupture rates of between 2% and 10% have been reported in the literature, little is known about the natural history and behavior of these lesions in patients with liver disease. Interventional management options pose a challenge given the high anesthetic and surgical risk of such patients. This study was conducted to study the management of all SAAs diagnosed among patients presenting for a liver transplant assessment at a single center over a three‐yr period. We discuss the presentation and management options, with elective and emergent presentation of SAA in patients with end‐stage liver disease.
Diversity in Mycotoxins and Fungal Species Infecting Wheat in Nakuru District, Kenya
Authors: Wagacha John Maina , Steiner Ulrike , Dehne Heinz‐Wilhelm , Zuehlke Sebastian , Spiteller Michael , Muthomi James , Oerke Erich‐Christian
Published: January 2010

Mycotoxin contamination of wheat kernels and diversity of fungal pathogens were monitored in a survey of 26 fields in Nakuru district, Kenya, in 2006. Sampling was performed twice; at mid‐anthesis in July for leaves, stems and spikelets and at harvest in September for spikelets and kernels. Kernels were analysed for the occurrence of 32 mycotoxins using a high performance liquid chromatography – electrospray tandem mass spectrometry (LC‐ESI‐MS/MS) method. Fungi were isolated from surface‐sterilized tissues and differentiated morphologically to the genus level. Fusarium isolates were identified based on the sequence of translation elongation factor 1‐alpha gene. Eleven Fusarium‐related mycotoxins were quantified with deoxynivalenol being detected at highest frequency (69%) and highest concentrations. Occurrence of enniatins in wheat (50%) is reported for the first time in Kenya. Non‐Fusarium mycotoxins detected included aflatoxin G2, ochratoxin A, alternariol and alternariol monomethyl ether. Prevalence of Fusarium species on different wheat parts was 100% at both growth stages. Nineteen Fusarium species were identified with seven species –Fusarium chlamydosporum, Fusarium boothi, Fusarium poae, Fusarium scirpi, Fusarium arthrosporioides, Fusarium oxysporum and Fusarium graminearum– accounting for 80% of infections. At anthesis, spikelets and leaves were the most and least susceptible tissue, respectively. At harvest, infection of spikelets was 59% higher than that of kernels.