bluuebunny/crossref_metadata_2025 huggingface dataset:
Cross modulation of whistler mode and HF waves above the HAARP ionospheric heater
Authors: Golkowski M. , Inan U. S. , Cohen M. B.
Published: August 2009

The HF facility of the High Frequency Active Auroral Research Program (HAARP) is employed to generate ELF/VLF radiation by modulation of overhead auroral electrojet currents for magnetospheric wave injection and propagation in the Earth‐ionosphere waveguide. HAARP induced ducted magnetospherically amplified whistler mode signals are observed to return to the vicinity of the HF facility and experience cross modulation with simultaneous HF transmissions. The cross modulation effect results from modification of the attenuation properties of the ionospheric medium by HAARP HF waves in the daytime ionosphere. The cross modulation concept is subsequently investigated as a new method for ELF/VLF wave generation with the HAARP heating facility using two co‐located HF beams. The new generation method is observed to generate radiation from 630 Hz–37 kHz. Observed amplitudes are an order of magnitude lower than fundamental frequencies generated using conventional AM, but of the same order as AM second harmonics.
Letting the Cat Out of the Bag: *OBO and the Semantic Web
Authors: Rose John
Published: August 2009

The tools developed to work with an expanding number of biomedical ontologies are all directed “inward,” back toward the scientists. The Semantic Web is an effort to assign meaning to data available on the internet resulting in a universal platform of knowledge exchange. For the Open Biomedical Ontologies to become a part of the Semantic Web, a more “outward-looking” tool is required. A prototype, AmiGA, based on 21 ontologies with over 600,000 terms,has been constructed.
A framework for quantifying water extraction and water stress responses of perennial lucerne
Authors: Brown Hamish E. , Moot Derrick J. , Fletcher Andrew L. , Jamieson Peter D.
Published: August 2009

A generic framework was developed and validated for predicting the water extraction and water stress responses of perennial lucerne (Medicago sativa) to improve existing crop models. Perennial forages have roots established throughout a soil profile so require a different approach to quantify water extraction patterns than annual crops. Two years of experimental data from two fields in New Zealand, each containing dryland and irrigated lucerne crops, were analysed to develop the theory of the water extraction framework. This showed that the temporal pattern of water extraction was consistent and each year commenced in the shallowest layer and progressed downward. Water extraction from each soil layer was quantified as the minimum of soil water supply and crop demand for that layer. For each soil layer, water demand was represented by transpiration demand (the product of potential evapotranspiration and crop cover) minus the sum of water extraction in overlying layers. This approach gave accurate descriptions of water extraction patterns over a range of rainfall and irrigation situations. Water supply from each soil layer (l) was quantified as the product of plant-available water and an extraction rate constant (kll). The kll of lucerne could not be calculated using the traditional curve-fitting procedure so kll was calculated by integrating the water extraction framework described above with a soil water balance and fitting kll to minimise residuals for water extraction predictions in each soil layer. This gave kll values that decreased from 0.035/day in the 0–0.2 m layer of soil to 0.01/day in the deepest layer measured (1.8–2.3 m). The water extraction framework was validated against another 3 years of dryland and irrigated lucerne data and gave accurate predictions of water extraction patterns throughout the soil profile. Water stress was quantified from actual transpiration relative to transpiration demand (T/TD). The most sensitive variable was leaf area expansion, which decreased from an optimum at T/TD = 1 to zero at T/TD = 0.2, followed by radiation-use efficiency, which decreased from an optimum at T/TD = 1 to zero at a T/TD of zero. The framework for quantifying water extraction and the techniques determined for identifying appropriate parameters to measure and characterise the framework are expected to be generally applicable to perennial forages in a wide range of environments.
Opposite roles of metastasin (S100A4) in two potentially tumoricidal mechanisms involving human lymphocyte protein Tag7 and Hsp70
Authors: Dukhanina Elena A. , Kabanova Olga D. , Lukyanova Tamara I. , Shatalov Yury V. , Yashin Denis V. , Romanova Elena A. , Gnuchev Nikolai V. , Galkin Alexander V. , Georgiev Georgii P. , Sashchenko Lidia P.
Published: August 2009

We compare the physical and functional interactions between three widespread multifunctional proteins [metastasin (Mts1/S100A4), innate immunity-related Tag7/PGRP-S, and Hsp70] in two experimental models relevant to host–tumor relationships on humoral and cellular levels. (
i
) Tag7 and Hsp70 in solution or in a lymphocyte make a stable binary complex that is highly cytotoxic for some tumor cells. Here, we show that Mts1 prevents Tag7·Hsp70 assembly in solution, and an excess of Mts1 disrupts the existing Tag7·Hsp70 complex; accordingly, Tag7·Hsp70 cytotoxicity (exemplified with L929 cells) is diminished in the presence of excess Mts1. (
ii
) Tag7 exposed on a specialized subset of lymphokine-activated killer cells makes specific contact with Hsp70 exposed on some HLA-negative tumor cells, thus enabling FasL/Fas-mediated induction of apoptosis. Here, we show that some CD4
+
CD25
+
cells coexpose Mts1 with Tag7 and FasL, that Mts1 and Tag7 closely contact the same Hsp70 molecule on the target K562 cell (as evidenced by cross-linking), and that killing of such targets is abolished by Mts1-specific antibodies (or selective removal of Mts1-exposing lymphocytes). Thus, this phenotype active against immunoevasive cancerous cells is defined as CD4
+
CD25
+
, FasL
+
, Tag7
+
Mts1
+
(≈0.5% of total lymphocytes in culture). Remarkably, similar effectors with at least the same activity are often found in fresh donor blood samples (≈10
4
effectors/mL). Thus, our models suggest that interactions between the three proteins in different situations may have opposite functional outcomes as regards antitumor defense, immune escape, and metastasis.
Epidemiological benefits of more-effective tuberculosis vaccines, drugs, and diagnostics
Authors: Abu-Raddad Laith J. , Sabatelli Lorenzo , Achterberg Jerusha T. , Sugimoto Jonathan D. , Longini Ira M. , Dye Christopher , Halloran M. Elizabeth
Published: August 2009

The Bill and Melinda Gates Foundation supports an ambitious portfolio of novel vaccines, drug regimens, and diagnostic tools for tuberculosis (TB). We elicited the expected efficacies and improvements of the novel interventions in discussions with the foundations managing their development. Using an age-structured mathematical model of TB, we explored the potential benefits of novel interventions under development and those not yet in the portfolio, focusing on the WHO Southeast Asia region. Neonatal vaccination with the portfolio vaccine decreases TB incidence by 39% to 52% by 2050. Drug regimens that shorten treatment duration and are efficacious against drug-resistant strains reduce incidence by 10–27%. New diagnostics reduce incidence by 13–42%. A triple combination of a portfolio vaccine, drug regimen, and diagnostics reduces incidence by 71%. A short mass vaccination catch-up campaign, not yet in the portfolio, to augment the triple combination, accelerates the decrease, preventing >30% more cases by 2050 than just the triple combination. New vaccines and drug regimens targeted at the vast reservoir of latently infected people, not in the portfolio, would reduce incidence by 37% and 82%, respectively. The combination of preventive latent therapy and a 2-month drug treatment regimen reduces incidence by 94%. Novel technologies in the pipeline would achieve substantial reductions in TB incidence, but not the Stop TB Partnership target for elimination. Elimination will require new delivery strategies, such as mass vaccination campaigns, and new products targeted at latently infected people.
Complex population structure in African village dogs and its implications for inferring dog domestication history
Authors: Boyko Adam R. , Boyko Ryan H. , Boyko Corin M. , Parker Heidi G. , Castelhano Marta , Corey Liz , Degenhardt Jeremiah D. , Auton Adam , Hedimbi Marius , Kityo Robert , Ostrander Elaine A. , Schoenebeck Jeffrey , Todhunter Rory J. , Jones Paul , Bustamante Carlos D.
Published: August 2009

High genetic diversity of East Asian village dogs has recently been used to argue for an East Asian origin of the domestic dog. However, global village dog genetic diversity and the extent to which semiferal village dogs represent distinct, indigenous populations instead of admixtures of various dog breeds has not been quantified. Understanding these issues is critical to properly reconstructing the timing, number, and locations of dog domestication. To address these questions, we sampled 318 village dogs from 7 regions in Egypt, Uganda, and Namibia, measuring genetic diversity >680 bp of the mitochondrial D-loop, 300 SNPs, and 89 microsatellite markers. We also analyzed breed dogs, including putatively African breeds (Afghan hounds, Basenjis, Pharaoh hounds, Rhodesian ridgebacks, and Salukis), Puerto Rican street dogs, and mixed breed dogs from the United States. Village dogs from most African regions appear genetically distinct from non-native breed and mixed-breed dogs, although some individuals cluster genetically with Puerto Rican dogs or United States breed mixes instead of with neighboring village dogs. Thus, African village dogs are a mosaic of indigenous dogs descended from early migrants to Africa, and non-native, breed-admixed individuals. Among putatively African breeds, Pharaoh hounds, and Rhodesian ridgebacks clustered with non-native rather than indigenous African dogs, suggesting they have predominantly non-African origins. Surprisingly, we find similar mtDNA haplotype diversity in African and East Asian village dogs, potentially calling into question the hypothesis of an East Asian origin for dog domestication.
Perturbations to trophic interactions and the stability of complex food webs
Authors: O'Gorman Eoin J. , Emmerson Mark C.
Published: August 2009

The pattern of predator–prey interactions is thought to be a key determinant of ecosystem processes and stability. Complex ecological networks are characterized by distributions of interaction strengths that are highly skewed, with many weak and few strong interactors present. Theory suggests that this pattern promotes stability as weak interactors dampen the destabilizing potential of strong interactors. Here, we present an experimental test of this hypothesis and provide empirical evidence that the loss of weak interactors can destabilize communities in nature. We ranked 10 marine consumer species by the strength of their trophic interactions. We removed the strongest and weakest of these interactors from experimental food webs containing >100 species. Extinction of strong interactors produced a dramatic trophic cascade and reduced the temporal stability of key ecosystem process rates, community diversity and resistance to changes in community composition. Loss of weak interactors also proved damaging for our experimental ecosystems, leading to reductions in the temporal and spatial stability of ecosystem process rates, community diversity, and resistance. These results highlight the importance of conserving species to maintain the stabilizing pattern of trophic interactions in nature, even if they are perceived to have weak effects in the system.
Formidability and the logic of human anger
Authors: Sell Aaron , Tooby John , Cosmides Leda
Published: August 2009

Eleven predictions derived from the recalibrational theory of anger were tested. This theory proposes that anger is produced by a neurocognitive program engineered by natural selection to use bargaining tactics to resolve conflicts of interest in favor of the angry individual. The program is designed to orchestrate two interpersonal negotiating tactics (conditionally inflicting costs or conditionally withholding benefits) to incentivize the target of the anger to place greater weight on the welfare of the angry individual. Individuals with enhanced abilities to inflict costs (e.g., stronger individuals) or to confer benefits (e.g., attractive individuals) have a better bargaining position in conflicts; hence, it was predicted that such individuals will be more prone to anger, prevail more in conflicts of interest, and consider themselves entitled to better treatment. These predictions were confirmed. Consistent with an evolutionary analysis, the effect of strength on anger was greater for men and the effect of attractiveness on anger was greater for women. Also as predicted, stronger men had a greater history of fighting than weaker men, and more strongly endorsed the efficacy of force to resolve conflicts—both in interpersonal and international conflicts. The fact that stronger men favored greater use of military force in international conflicts provides evidence that the internal logic of the anger program reflects the ancestral payoffs characteristic of a small-scale social world rather than rational assessments of modern payoffs in large populations.
A crystal structure of a dimer of the antibiotic ramoplanin illustrates membrane positioning and a potential Lipid II docking interface
Authors: Hamburger James B. , Hoertz Amanda J. , Lee Amy , Senturia Rachel J. , McCafferty Dewey G. , Loll Patrick J.
Published: August 2009

The glycodepsipeptide antibiotic ramoplanin A2 is in late stage clinical development for the treatment of infections from Gram-positive pathogens, especially those that are resistant to first line antibiotics such as vancomycin. Ramoplanin A2 achieves its antibacterial effects by interfering with production of the bacterial cell wall; it indirectly inhibits the transglycosylases responsible for peptidoglycan biosynthesis by sequestering their Lipid II substrate. Lipid II recognition and sequestration occur at the interface between the extracellular environment and the bacterial membrane. Therefore, we determined the structure of ramoplanin A2 in an amphipathic environment, using detergents as membrane mimetics, to provide the most physiologically relevant structural context for mechanistic and pharmacological studies. We report here the X-ray crystal structure of ramoplanin A2 at a resolution of 1.4 Å. This structure reveals that ramoplanin A2 forms an intimate and highly amphipathic dimer and illustrates the potential means by which it interacts with bacterial target membranes. The structure also suggests a mechanism by which ramoplanin A2 recognizes its Lipid II ligand.
Mutation I810N in the α3 isoform of Na
+
,K
+
-ATPase causes impairments in the sodium pump and hyperexcitability in the CNS
Authors: Clapcote Steven J. , Duffy Steven , Xie Gang , Kirshenbaum Greer , Bechard Allison R. , Rodacker Schack Vivien , Petersen Janne , Sinai Laleh , Saab Bechara J. , Lerch Jason P. , Minassian Berge A. , Ackerley Cameron A. , Sled John G. , Cortez Miguel A. , Henderson Jeffrey T. , Vilsen Bente , Roder John C.
Published: August 2009

In a mouse mutagenesis screen, we isolated a mutant,
Myshkin
(
Myk
), with autosomal dominant complex partial and secondarily generalized seizures, a greatly reduced threshold for hippocampal seizures in vitro, posttetanic hyperexcitability of the CA3-CA1 hippocampal pathway, and neuronal degeneration in the hippocampus. Positional cloning and functional analysis revealed that
Myk
/+ mice carry a mutation (I810N) which renders the normally expressed Na
+
,K
+
-ATPase α3 isoform inactive. Total Na
+
,K
+
-ATPase activity was reduced by 42% in
Myk
/+ brain. The epilepsy in
Myk
/+ mice and in vitro hyperexcitability could be prevented by delivery of additional copies of wild-type Na
+
,K
+
-ATPase α3 by transgenesis, which also rescued Na
+
,K
+
-ATPase activity. Our findings reveal the functional significance of the Na
+
,K
+
-ATPase α3 isoform in the control of epileptiform activity and seizure behavior.
The malarial parasite
Plasmodium falciparum
imports the human protein peroxiredoxin 2 for peroxide detoxification
Authors: Koncarevic Sasa , Rohrbach Petra , Deponte Marcel , Krohne Georg , Prieto Judith Helena , Yates John , Rahlfs Stefan , Becker Katja
Published: August 2009

Coevolution of the malarial parasite and its human host has resulted in a complex network of interactions contributing to the homeodynamics of the host-parasite unit. As a rapidly growing and multiplying organism,
Plasmodium falciparum
depends on an adequate antioxidant defense system that is efficient despite the absence of genuine catalase and glutathione peroxidase. Using different experimental approaches, we demonstrate that
P. falciparum
imports the human redox-active protein peroxiredoxin 2 (hPrx-2, hTPx1) into its cytosol. As shown by confocal microscopy and immunogold electron microscopy, hPrx-2 is also present in the Maurer's clefts, organelles that are described as being involved in parasite protein export. Enzyme kinetic analyses prove that hPrx-2 accepts
Plasmodium
cytosolic thioredoxin 1 as a reducing substrate. hPrx-2 accounts for roughly 50% of thioredoxin peroxidase activity in parasite extracts, thus indicating a functional role of hPrx-2 as an enzymatic scavenger of peroxides in the parasite. Under chloroquine treatment, a drug promoting oxidative stress, the abundance of hPrx-2 in the parasite increases significantly.
P. falciparum
has adapted to adopt the hPrx-2, thereby using the host protein for its own purposes.
Conservation of enhancer location in divergent insects
Authors: Cande Jessica , Goltsev Yury , Levine Michael S.
Published: August 2009

Dorsoventral (DV) patterning of the
Drosophila
embryo is controlled by a concentration gradient of Dorsal, a sequence-specific transcription factor related to mammalian NF-κB. The Dorsal gradient generates at least 3 distinct thresholds of gene activity and tissue specification by the differential regulation of target enhancers containing distinctive combinations of binding sites for Dorsal, Twist, Snail, and other DV determinants. To understand the evolution of DV patterning mechanisms, we identified and characterized Dorsal target enhancers from the mosquito
Anopheles gambiae
and the flour beetle
Tribolium castaneum
. Putative orthologous enhancers are located in similar positions relative to the target genes they control, even though they lack sequence conservation and sometimes produce divergent patterns of gene expression. The most dramatic example of this conservation is seen for the “shadow” enhancer regulating
brinker
: It is conserved within the intron of the neighboring
Atg5
locus of both flies and mosquitoes. These results suggest that, like exons, an enhancer position might be subject to constraint. Thus, novel patterns of gene expression might arise from the modification of conserved enhancers rather than the invention of new ones. We propose that this enhancer constancy might be a general property of regulatory evolution, and should facilitate enhancer discovery in nonmodel organisms.
Restoring a maize root signal that attracts insect-killing nematodes to control a major pest
Authors: Degenhardt Jörg , Hiltpold Ivan , Köllner Tobias G. , Frey Monika , Gierl Alfons , Gershenzon Jonathan , Hibbard Bruce E. , Ellersieck Mark R. , Turlings Ted C. J.
Published: August 2009

When attacked by herbivorous insects, plants emit volatile compounds that attract natural enemies of the insects. It has been proposed that these volatile signals can be manipulated to improve crop protection. Here, we demonstrate the full potential of this strategy by restoring the emission of a specific belowground signal emitted by insect-damaged maize roots. The western corn rootworm induces the roots of many maize varieties to emit (
E
)-β-caryophyllene, which attracts entomopathogenic nematodes that infect and kill the voracious root pest. However, most North American maize varieties have lost the ability to emit (
E
)-β-caryophyllene and may therefore receive little protection from the nematodes. To restore the signal, a nonemitting maize line was transformed with a (
E
)-β-caryophyllene synthase gene from oregano, resulting in constitutive emissions of this sesquiterpene. In rootworm-infested field plots in which nematodes were released, the (
E
)-β-caryophyllene-emitting plants suffered significantly less root damage and had 60% fewer adult beetles emerge than untransformed, nonemitting lines. This demonstration that plant volatile emissions can be manipulated to enhance the effectiveness of biological control agents opens the way for novel and ecologically sound strategies to fight a variety of insect pests.
CK2 negatively regulates Gαssignaling
Authors: Rebholz Heike , Nishi Akinori , Liebscher Sabine , Nairn Angus C. , Flajolet Marc , Greengard Paul
Published: August 2009

We present evidence, using biochemical and cellular approaches, that the kinase, CK2, negatively controls signaling via Gαs(or Gαolf) coupled to dopamine D1 and adenosine A2A receptors. Pharmacological inhibition of CK2 or CK2 knockdown by RNAi lead to elevated cAMP levels in dopamine D1 receptor-activated neuroblastoma cells. Phosphorylation levels of protein kinase A substrates were increased in the presence of CK2 inhibitors in mouse striatal slices. The effect of D1 receptor and A2A receptor agonists on the phosphorylation of protein kinase A sites was potentiated upon CK2 inhibition. Furthermore, in cell lines, we observed that reduction in CK2 activity, pharmacologically or genetically, reduced the amount of D1 receptor that was internalized in response to dopamine. Finally, the β subunit of CK2 was found to interact specifically with the Gαssubunit through protein interaction analyses. Thus CK2 can inhibit G protein-coupled receptor action by enabling faster receptor internalization, possibly through a direct association with Gαs.
A possible effector role for the pleckstrin homology (PH) domain of dynamin
Authors: Bethoney Kelley A. , King Megan C. , Hinshaw Jenny E. , Ostap E. Michael , Lemmon Mark A.
Published: August 2009

The large GTPase dynamin plays a key role in clathrin-mediated endocytosis in animal cells, although its mechanism of action remains unclear. Dynamins 1, 2, and 3 contain a pleckstrin homology (PH) domain that binds phosphoinositides with a very low affinity (K
D
> 1 mM), and this interaction appears to be crucial for function. These observations prompted the suggestion that an array of PH domains drives multivalent binding of dynamin oligomers to phosphoinositide-containing membranes. Although in vitro experiments reported here are consistent with this hypothesis, we find that PH domain mutations that abolish dynamin function do not alter localization of the protein in transfected cells, indicating that the PH domain does not play a simple targeting role. An alternative possibility is suggested by the geometry of dynamin helices resolved by electron microscopy. Even with one phosphatidylinositol-4,5-bisphosphate [PtdIns(
4
,
5
)
P
2
] molecule bound per PH domain, these dynamin assemblies will elevate the concentration of PtdIns(
4
,
5
)
P
2
at coated pit necks, and effectively cluster (or sequester) this phosphoinositide. In vitro fluorescence quenching studies using labeled phosphoinositides are consistent with dynamin-induced PtdIns(
4
,
5
)
P
2
clustering. We therefore propose that the ability of dynamin to alter the local distribution of PtdIns(
4
,
5
)
P
2
could be crucial for the role of this GTPase in promoting membrane scission during clathrin-mediated endocytosis. PtdIns(
4
,
5
)
P
2
clustering could promote vesicle scission through direct effects on membrane properties, or might play a role in dynamin's ability to regulate actin polymerization.
Pivotal role of dihydrofolate reductase knockdown in the anticancer activity of 2-hydroxyoleic acid
Authors: Lladó Victoria , Terés Silvia , Higuera Mónica , Álvarez Rafael , Noguera-Salva Maria Antònia , Halver John E. , Escribá Pablo V. , Busquets Xavier
Published: August 2009

α-Hydroxy-9-
cis
-octadecenoic acid, a synthetic fatty acid that modifies the composition and structure of lipid membranes. 2-Hydroxyoleic acid (HOA) generated interest due to its potent, yet nontoxic, anticancer activity. It induces cell cycle arrest in human lung cancer (A549) cells and apoptosis in human leukemia (Jurkat) cells. These two pathways may explain how HOA induces regression of a variety of cancers. We showed that HOA repressed the expression of dihydrofolate reductase (DHFR), the enzyme responsible for tetrahydrofolate (THF) synthesis. Folinic acid, which readily produces THF without the participation of DHFR, reverses the antitumor effects of HOA in A549 and Jurkat cells, as well as the inhibitory influence on cyclin D and cdk2 in A549 cells, and on DNA and PARP degradation in Jurkat cells. This effect was very specific, because either elaidic acid (an analog of HOA) or other lipids, failed to alter A549 or Jurkat cell growth. THF is a cofactor necessary for DNA synthesis. Thus, impairment of DNA synthesis appears to be a common mechanism involved in the different responses elicited by cancer cells following treatment with HOA, namely cell cycle arrest or apoptosis. Compared with other antifolates, such as methotrexate, HOA did not directly inhibit DHFR but rather, it repressed its expression, a mode of action that offers certain therapeutic advantages. These results not only demonstrate the effect of a fatty acid on the expression of DHFR, but also emphasize the potential of HOA to be used as a wide-spectrum drug against cancer.
The autophagy machinery is required to initiate hepatitis C virus replication
Authors: Dreux Marlène , Gastaminza Pablo , Wieland Stefan F. , Chisari Francis V.
Published: August 2009

In addition to its cellular homeostasis function, autophagy is emerging as a central component of antimicrobial host defense against diverse infections. To counteract this mechanism, many pathogens have evolved to evade, subvert, or exploit autophagy. Here, we report that autophagy proteins (i.e., Beclin-1, Atg4B, Atg5, and Atg12) are proviral factors required for translation of incoming hepatitis C virus (HCV) RNA and, thereby, for initiation of HCV replication, but they are not required once infection is established. These results illustrate a previously unappreciated role for autophagy in the establishment of a viral infection and they suggest that different host factors regulate the translation of incoming viral genome and translation of progeny HCV RNA once replication is established.
The origin of malignant malaria
Authors: Rich Stephen M. , Leendertz Fabian H. , Xu Guang , LeBreton Matthew , Djoko Cyrille F. , Aminake Makoah N. , Takang Eric E. , Diffo Joseph L. D. , Pike Brian L. , Rosenthal Benjamin M. , Formenty Pierre , Boesch Christophe , Ayala Francisco J. , Wolfe Nathan D.
Published: August 2009

Plasmodium falciparum
, the causative agent of malignant malaria, is among the most severe human infectious diseases. The closest known relative of
P. falciparum
is a chimpanzee parasite,
Plasmodium reichenowi
, of which one single isolate was previously known. The co-speciation hypothesis suggests that both parasites evolved separately from a common ancestor over the last 5–7 million years, in parallel with the divergence of their hosts, the hominin and chimpanzee lineages. Genetic analysis of eight new isolates of
P. reichenowi
, from wild and wild-born captive chimpanzees in Cameroon and Côte d'Ivoire, shows that
P. reichenowi
is a geographically widespread and genetically diverse chimpanzee parasite. The genetic lineage comprising the totality of global
P. falciparum
is fully included within the much broader genetic diversity of
P. reichenowi
. This finding is inconsistent with the co-speciation hypothesis. Phylogenetic analysis indicates that all extant
P. falciparum
populations originated from
P. reichenowi
, likely by a single host transfer, which may have occurred as early as 2–3 million years ago, or as recently as 10,000 years ago. The evolutionary history of this relationship may be explained by two critical genetic mutations. First, inactivation of the
CMAH
gene in the human lineage rendered human ancestors unable to generate the sialic acid Neu5Gc from its precursor Neu5Ac, and likely made humans resistant to
P. reichenowi
. More recently, mutations in the dominant invasion receptor EBA 175 in the
P. falciparum
lineage provided the parasite with preference for the overabundant Neu5Ac precursor, accounting for its extreme human pathogenicity.
Self-organization of keratin intermediate filaments into cross-linked networks
Authors: Lee Chang-Hun , Coulombe Pierre A.
Published: August 2009

Keratins, the largest subgroup of intermediate filament (IF) proteins, form a network of 10-nm filaments built from type I/II heterodimers in epithelial cells. A major function of keratin IFs is to protect epithelial cells from mechanical stress. Like filamentous actin, keratin IFs must be cross-linked in vitro to achieve the high level of mechanical resilience characteristic of live cells. Keratins 5 and 14 (K5 and K14), the main pairing occurring in the basal progenitor layer of epidermis and related epithelia, can readily self-organize into large filament bundles in vitro and in vivo. Here, we show that filament self-organization is mediated by multivalent interactions involving distinct regions in K5 and K14 proteins. Self-organization is determined independently of polymerization into 10-nm filaments, but involves specific type I–type II keratin complementarity. We propose that self-organization is a key determinant of the structural support function of keratin IFs in vivo.
piRNAs mediate posttranscriptional retroelement silencing and localization to pi-bodies in the Drosophila germline
Authors: Lim Ai Khim , Tao Liheng , Kai Toshie
Published: August 2009

Nuage, a well-conserved perinuclear organelle found in germline cells, is thought to mediate retroelement repression in Drosophila melanogaster by regulating the production of Piwi-interacting RNAs (piRNAs). In this study, we present evidence that the nuage–piRNA pathway components can be found in cytoplasmic foci that also contain retroelement transcripts, antisense piRNAs, and proteins involved in messenger RNA (mRNA) degradation. These mRNA degradation proteins, decapping protein 1/2 (DCP1/2), Me31B (maternal expression at 31B), and pacman (PCM), are normally thought of as components of processing bodies. In spindle-E (spn-E) and aubergine (aub) mutants that lack piRNA production, piRNA pathway proteins no longer overlap the mRNA degradation proteins. Concomitantly, spn-E and aub mutant ovaries show an accumulation of full-length retroelement transcripts and prolonged stabilization of HeT-A mRNA, supporting the role of piRNAs in mediating posttranscriptional retroelement silencing. HeT-A mRNA is derepressed in mRNA degradation mutants twin, dcp1, and ski3, indicating that these enzymes also aid in removing full-length transcripts and/or decay intermediates.
Dystrophin is a microtubule-associated protein
Authors: Prins Kurt W. , Humston Jill L. , Mehta Amisha , Tate Victoria , Ralston Evelyn , Ervasti James M.
Published: August 2009

Cytolinkers are giant proteins that can stabilize cells by linking actin filaments, intermediate filaments, and microtubules (MTs) to transmembrane complexes. Dystrophin is functionally similar to cytolinkers, as it links the multiple components of the cellular cytoskeleton to the transmembrane dystroglycan complex. Although no direct link between dystrophin and MTs has been documented, costamere-associated MTs are disrupted when dystrophin is absent. Using tissue-based cosedimentation assays on mice expressing endogenous dystrophin or truncated transgene products, we find that constructs harboring spectrinlike repeat 24 through the first third of the WW domain cosediment with MTs. Purified Dp260, a truncated isoform of dystrophin, bound MTs with a Kd of 0.66 µM, a stoichiometry of 1 Dp260/1.4 tubulin heterodimer at saturation, and stabilizes MTs from cold-induced depolymerization. Finally, α- and β-tubulin expression is increased ∼2.5-fold in mdx skeletal muscle without altering the tubulin–MT equilibrium. Collectively, these data suggest dystrophin directly organizes and/or stabilizes costameric MTs and classifies dystrophin as a cytolinker in skeletal muscle.
Pseudo-Outbreak of “Mycobacterium paraffinicum” Infection and/or Colonization in a Tertiary Care Medical Center
Authors: Wang Shu-Hua , Pancholi Preeti , Stevenson Kurt , Yakrus Mitchell A. , Butler W. Ray , Schlesinger Larry S. , Mangino Julie E.
Published: August 2009

Objective.

To investigate a pseudo-outbreak of “Mycobacterium paraffinicum” (unofficial taxon) infection and/or colonization, using isolates recovered from clinical and environmental specimens.

Design.

Outbreak investigation.

Setting.

University-affiliated, tertiary-care hospital.

Methods.

M. paraffinicum, a slow-growing, nontuberculous species of mycobacteria, was recovered from 21 patients and an ice machine on a single patient care unit over a 2.5-year period. The clinical, epidemiological, and environmental investigation of this pseudo-outbreak is described.

Results.

Twenty-one patients with pulmonary symptoms and possible risk factors for tuberculosis were admitted to inpatient rooms that provided airborne isolation conditions in 2 adjacent hospital buildings. In addition, 1 outpatient had induced sputum cultured for mycobacteria in the pulmonary function laboratory. Of the samples obtained from these 21 patients, 26 isolates from respiratory samples and 1 isolate from a stool sample were identified asM. paraffinicum. Environmental isolates obtained from an ice machine in the patient care unit where the majority of the patients were admitted were also identified asM. paraffinicum.

Conclusions.

An epidemiological investigation that used molecular tools confirmed the suspicion of a pseudo-outbreak ofM. paraffinicuminfection and/or colonization. The hospital water system was identified as the source of contamination.
Comparative cladistics
Authors: Sereno Paul C.
Published: August 2009

Current strategies to compare or synthesize morphology‐based cladistic hypotheses do not empower individual cladists to (i) understand the origin, authorship, or structure of character data, (ii) efficiently locate and collate previously published character data, or (iii) effectively compare character data from competing cladistic hypotheses. This paper outlines the requisite terminology, methods and indices to effectively compile and compare morphological character data between competing cladistic hypotheses and to isolate and measure the most important factors behind differing cladistic results—character selection and character‐state scoring. When the procedures outlined here are facilitated by appropriate software, morphology‐based cladistics may overcome long‐recognized limitations in data comparison and synthesis.
Alcohol and Russian mortality: a continuing crisis
Authors: Leon David A. , Shkolnikov Vladimir M. , McKee Martin
Published: August 2009

Background  Russia remains in the grip of a mortality crisis in which alcohol plays a central role. In 2007, male life expectancy at birth was 61 years, while for females it was 74 years. Alcohol is implicated particularly in deaths among working‐age men.

Aims  To review the current state of knowledge about the contribution of alcohol to the continuing very high mortality seen among Russian adults

Results  Conservative estimates attribute 31–43% of deaths among working‐age men to alcohol. This latter estimate would imply a minimum of 170 000 excess deaths due to hazardous alcohol consumption in Russia per year. Men drink appreciably more than women in Russia. Hazardous drinking is most prevalent among people with low levels of education and those who are economically disadvantaged, partly because some of the available sources of ethanol are very cheap and easy to obtain. The best estimates available suggest that per capita consumption among adults is 15–18 litres of pure ethanol per year. However, reliable estimation of the total volume of alcohol consumed per capita in Russia is very difficult because of the diversity of sources of ethanol that are available, for many of which data do not exist. These include both illegal spirits, as well as legal non‐beverage alcohols (such as medicinal tinctures). In 2006 regulations were introduced aimed at reducing the production and sale of non‐beverage alcohols that are commonly drunk. These appear to have been only partially successful.

Conclusion  There is convincing evidence that alcohol plays an important role in explaining high mortality in Russia, in particular among working age men. However, there remain important uncertainties about the precise scale of the problem and about the health effects of the distinctive pattern of alcohol consumption that is prevalent in Russia today. While there is a need for further research, enough is known to justify the development of a comprehensive inter‐sectoral alcohol control strategy. The recent fall in life expectancy in Russia should give a renewed urgency to attempts to move the policy agenda forward.
Preventing growth in amphetamine use: long‐term effects of the Midwestern Prevention Project (MPP) from early adolescence to early adulthood
Authors: Riggs Nathaniel R. , Chou Chih‐Ping , Pentz Mary Ann
Published: August 2009

Aim  The aim of the current study was to examine the long‐term effect of an early adolescent substance abuse prevention program on trajectories and initiation of amphetamine use into early adulthood.

Design  Eight middle schools were assigned randomly to a program or control condition. The randomized controlled trial followed participants through 15 waves of data, from ages 11–28 years. This longitudinal study design includes four separate periods of development from early adolescence to early adulthood.

Setting  The intervention took place in middle schools.

Participants  A total of 1002 adolescents from one large mid‐western US city were the participants in the study.

Intervention  The intervention was a multi‐component community‐based program delivered in early adolescence with a primary emphasis on tobacco, alcohol and marijuana use.

Measures  At each wave of data collection participants completed a self‐report survey that included questions about life‐time amphetamine use.

Findings  Compared to a control group, participants in the Midwestern Prevention Project (MPP) intervention condition had reduced growth (slope) in amphetamine use in emerging adulthood, a lower amphetamine use intercept at the commencement of the early adulthood and delayed amphetamine use initiation.

Conclusions  The pattern of results suggests that the program worked first to prevent amphetamine use, and then to maintain the preventive effect into adulthood. Study findings suggest that early adolescent substance use prevention programs that focus initially on the ‘gateway’ drugs have utility for long‐term prevention of amphetamine use.
Cigarettes and social differentiation in France: is tobacco use increasingly concentrated among the poor?
Authors: Peretti‐Watel Patrick , Constance Jean , Seror Valérie , Beck François
Published: August 2009

Aims  This paper aimed to assess whether the increase of social differentiation of smoking is observed in France.

Design and setting  Five cross‐sectional telephone surveys conducted in France between 2000 and 2007.

Participants  The surveys were conducted among national representative samples of French subjects aged 18–75 years (n = 12 256, n = 2906, n = 27 499, n = 2887, n = 6007 in 2000, 2003, 2005, 2006 and 2007, respectively). We focused on three groups: executives, manual workers and the unemployed.

Measurements  Time trends of smoking prevalence were assessed, and socio‐economic factors (especially occupation and job status) associated with smoking were identified and compared in 2000 and 2005. We also computed respondents' equivalized household consumption (EHI) and their cigarette budget to assess the financial burden of smoking.

Findings  Between 2000 and 2007, smoking prevalence decreased by 22% among executive managers and professionals and by 11% among manual workers, and did not decrease among the unemployed. Indicators of an underprivileged social situation were associated more markedly with smoking in 2005 than in 2000. In addition, the falling‐off of smoking initiation occurred later and was less marked among manual workers than it was among executive managers and professionals. Finally, in 2005 15% of French smokers devoted at least 20% of their EHI to the purchase of cigarettes, versus only 5% in 2000, and smoking weighted increasingly heavily on the poorest smokers' budgets.

Conclusions  While these results point out an increased social differentiation in tobacco use, they underline the need to design and implement other forms of action to encourage people to quit, in particular targeting individuals belonging to underprivileged groups.
Hypothalamic–pituitary–adrenal axis and smoking and drinking onset among adolescents: the longitudinal cohort TRacking Adolescents' Individual Lives Survey (TRAILS)
Authors: Huizink Anja C. , Greaves‐Lord Kirstin , Oldehinkel Albertine J. , Ormel Johan , Verhulst Frank C.
Published: August 2009

Aims  We examined within a prospective longitudinal study whether cortisol levels were associated with smoking or drinking behaviours, taking parental substance use into account.

Design  The influence of parental substance use on cortisol levels of their adolescent offspring at age 10–12 years was examined. Next, cortisol levels of adolescents who initiated smoking or drinking at the first data collection (age 10–12) were compared to non‐users. Finally, we examined whether cortisol levels could predict new onset and frequency of smoking and drinking 2 years later.

Setting and participants  First and second assessment data of the TRacking Adolescents' Individual Lives Survey (TRAILS) were used, including 1768 Dutch adolescents aged 10–12 years, who were followed‐up across a period of 2 years.

Measurements  Cortisol was measured in saliva samples at awakening, 30 minutes later, and at 8 p.m. at age 10–12. Self‐reported substance use at age 10–12 and 13–14, and parental self‐reported substance use were used.

Findings  Only maternal substance use was related to slightly lower adolescent cortisol levels at 8 p.m. Both maternal and paternal substance use were associated with adolescent smoking and drinking at age 13–14, although fathers' use only predicted the amount used and not the chance of ever use. Finally, higher cortisol levels were related moderately to current smoking and future frequency of smoking, but not to alcohol use.

Conclusions  In a general population, parental heavy substance use does not seem to affect cortisol levels consistently in their offspring. We found some evidence for higher, instead of lower, hypothalamic–pituitary–adrenal axis activity as a predictor of smoking in early adolescence.
The common exon 3 polymorphism of the growth hormone receptor gene and the effect of growth hormone therapy on growth in Korean patients with Turner syndrome
Authors: Ko Jung Min , Kim Jae‐Min , Cheon Chong‐Kun , Kim Duk‐Hee , Lee Dae‐Yeol , Cheong Woo Yeong , Kim Eun Young , Park Mi Jung , Yoo Han‐Wook
Published: August 2009

Objective  Recombinant human growth hormone (GH) can achieve final adult height gain in girls with Turner syndrome (TS), but its efficacy varies widely across individuals. The exon 3‐deleted polymorphism of growth hormone receptor (d3‐GHR) has been reported to be associated with responsiveness to GH therapy. The short‐term growth response of Turner patients to GH therapy was analysed according to their GHR‐exon 3 polymorphism genotype.

Design and patients  This was a retrospective study of 175 TS patients. Auxological and endocrine parameters were measured, and the GHR‐exon 3 genotype was analysed. Allelic frequencies of GHR‐exon 3 genotype were compared between patients with TS and control individuals. GH had been administered to 147 patients, 115 of which remained pre‐pubertal after the first follow‐up year. Changes in height standard deviation score (SDS), height velocity (HV), body mass index (BMI), IGF‐1 and IGF binding protein‐3 (IGFBP‐3) concentrations were compared between these patients, grouped according to genotype, after the first follow‐up year.

Results  There was no difference in GHR‐exon 3 genotype frequency between the TS and control groups of Koreans. According to the GHR‐exon 3 genotype (fl/fl group vs. d3/fl and d3/d3 group), HV gain and height SDS gain did not differ significantly at the first year of GH therapy. Moreover, changes in IGF‐1, IGFBP‐3 concentration and BMI showed no significant difference between the groups with and without d3‐GHR after 1 year of GH therapy.

Conclusion  The distribution of the GHR‐exon 3 genotype was similar in the TS and control groups in a Korean population. The growth promotion efficacy of GH therapy did not differ significantly between TS patients with and without the d3‐GHR allele. These findings indicate that the GHR‐exon 3 genotype may not be a major factor to affect the GH response in Korean Turner patients.
Influence of simulated climate change and eutrophication on three‐spined stickleback populations: a large scale mesocosm experiment
Authors: MORAN REBECCA , HARVEY IAN , MOSS BRIAN , FEUCHTMAYR HEIDRUN , HATTON KEITH , HEYES TOM , ATKINSON DAVID
Published: August 2009

1. Shallow lakes and their ectothermic inhabitants are particularly vulnerable to the effects of climatic warming. These impacts are likely to depend on nutrient loading, especially if the combination of warming and eutrophication leads to severe hypoxia.

2. To investigate effects of realistic warming and nutrient loading on a fish species with high tolerance of warming and hypoxia, we observed population changes and timing of reproduction of three‐spined sticklebacks in 24 outdoor shallow freshwater ecosystems with combinations of temperature (ambient and ambient +4 °C) and three nutrient treatments over 16 months.

3. Warming reduced stickleback population biomass by 60% (population size by 76%) and nutrient‐addition reduced biomass by about 80% (population size 95%). Nutrients and warming together resulted in extinction of the stickleback populations. These losses were mainly attributed to the increased likelihood of severe hypoxia in heated and nutrient‐addition mesocosms.

4. Warming of nutrient‐rich waters can thus have dire consequences for freshwater ectotherm populations. The loss even of a hardy fish suggests a precarious future for many less tolerant species in such eutrophic systems under current climate change predictions.