bluuebunny/crossref_metadata_2025 huggingface dataset:
Operational Street Pollution Model (OSPM) - a review of performed application and validation studies, and future prospects
Authors: Kakosimos Konstantinos E. , Hertel Ole , Ketzel Matthias , Berkowicz Ruwim
Published: December 2010

Environmental context Trafficked streets are air pollution hot spots where people experience high exposure to hazardous pollutants. Although monitoring networks provide crucial information about measured pollutant levels, the measurements are resource demanding and thus can be performed at only few selected sites. Fast and easily applied street pollution models are therefore necessary tools to provide information about the loadings in streets without measurement activities. We evaluate the Operational Street Pollution Model, one of the most commonly applied models in air pollution management and research worldwide. Abstract Traffic emissions constitute a major source of health hazardous air pollution in urban areas. Models describing pollutant levels in urban streets are thus important tools in air pollution management as a supplement to measurements in routine monitoring programmes. A widely used model in this context is the fast and easy to apply Operational Street Pollution Model (OSPM). For almost 20 years, OSPM has been routinely used in many countries for studying traffic pollution, performing analyses of field campaign measurements, studying efficiency of pollution abatement strategies, carrying out exposure assessments and as reference in comparisons to other models. OSPM is generally considered as state-of-the-art in applied street pollution modelling. This paper outlines the most important findings in OSPM validation and application studies in literature. At the end of the paper, future research needs are outlined for traffic air pollution modelling in general but with outset in the research performed with OSPM.
Nickel sulfide formation at low temperature: initial precipitates, solubility and transformation products
Authors: Wilkin Richard T. , Rogers David A.
Published: December 2010

Environmental context Remediation technologies often rely on manipulation of redox conditions or natural redox processes to favour microbial sulfate-reduction and mineral sulfide formation for treatment of inorganic contaminants in groundwater, including nickel. However, few data are available on the structural properties, solubility and mineral transformation processes involving nickel sulfides. These data are needed in order to constrain the long term performance of groundwater remediation efforts. Abstract The formation of nickel sulfides has been examined experimentally over the temperature range from 25 to 60°C. At all conditions studied, hexagonal (α-NiS) was the initial precipitate from solution containing Ni2+ and dissolved sulfide. Freshly precipitated nickel sulfide possesses significant residual Ni–O coordination as revealed by X-ray absorption spectroscopy. With progressive aging, residual Ni–O coordination is replaced by Ni–S coordination. The formation of millerite (β-NiS, rhombohedral) was not detected in any of the synthesis experiments. In the presence of elemental sulfur, hexagonal NiS converted to polydymite (Ni3S4) and vaesite (NiS2). Thus, conversion of nickel monosulfide to thiospinel and disulfide structures appears to be redox dependent, analogous to aging and transformation processes of iron sulfides. In the absence of elemental sulfur or with only hydrogen sulfide or bisulfide present, transformation of hexagonal NiS was not observed after 1680 h at 60°C. Low-pH solubility experiments yielded a solubility product for hexagonal NiS of log Ks0 = –2.69 ± 0.26. Solubility data at pH > 3 suggest that Ni–bisulfide complexation is important in controlling the solubility of Ni in sulfidic solutions.
Comparison of 1-D and 2-D NMR techniques for screening earthworm responses to sub-lethal endosulfan exposure
Authors: Yuk Jimmy , McKelvie Jennifer R. , Simpson Myrna J. , Spraul Manfred , Simpson André J.
Published: December 2010

Environmental context The application of metabolomics from an environmental perspective depends on the analytical ability to discriminate minute changes in the organism resulting from exposure. In this study, 1-D and 2-D Nuclear Magnetic Resonance (NMR) experiments were examined to characterise the earthworm’s metabolic response to an organochlorine pesticide. 2-D NMR showed considerable improvement in discriminating exposed worms from controls and in identifying the metabolites responsible. This study demonstrates the potential of 2-D NMR in understanding subtle biochemical responses resulting from environmental exposure. Abstract Nuclear Magnetic Resonance (NMR) based metabolomics is a powerful approach to monitoring an organism’s metabolic response to environmental exposure. However, the discrimination between exposed and control groups, depends largely on the NMR technique chosen. Here, three 1-D NMR and three 2-D NMR techniques were investigated for their ability to discriminate between control earthworms (Eisenia fetida) and those exposed to a sub-lethal concentration of a commonly occurring organochlorine pesticide, endosulfan. Partial least-squares discriminant analysis found 1H–13C Heteronuclear Single Quantum Coherence (HSQC) spectroscopy to have the highest discrimination with a MANOVA value (degree of separation) three orders lower than any of the 1-D and 2-D NMR techniques. HSQC spectroscopy identified alanine, leucine, lysine, glutamate, glucose and maltose as the major metabolites of exposure to endosulfan, more than all the other techniques combined. HSQC spectroscopy in combination with a shorter 1-D experiment may prove to be an effective tool for the discrimination and identification of significant metabolites in organisms under environmental stress.
Ex-post compensation payments for wolf predation on livestock in Italy: a tool for conservation?
Authors: Boitani Luigi , Ciucci Paolo , Raganella-Pelliccioni Elisabetta
Published: December 2010

Context. Compensation programs have become a common tool to mitigate conflicts between farmers and large predators; however, their effectiveness is based on a series of assumptions that should be carefully and continuously assessed within an adaptive management framework. Ex-post compensation programs were adopted in Italy as a financial incentive to aid wolf conservation since the 1970s; however, their implementation has never been monitored nor actively managed in the past 35 years, during which time a remarkable recovery of wolf population and range expansion into more human-dominated landscapes has taken place.
Aims. We hereby report on wolf-damage compensation programs in Italy and discuss their conservation value.
Methods. We used data on wolf-damage compensation that we compiled at the national scale for the period 1991–95. Although not recent, these were unfortunately the only available data at the national scale, and were instrumental in supporting our discussion on compensation programs, as these are increasingly becoming a politically and economically sensitive issue.
Key results. From 1991 to 1995, annual compensation costs represented on average 86% of the alleged losses to farmers, and averaged €1 825  440 (±169 760 s.d.), or about €5150 (±750) per wolf per year. Compensation costs varied markedly from region to region, although local differences were hardly explainable in terms of wolf densities and their trends at the regional scale. On the contrary, they appeared largely affected by inconsistencies in rules and procedures of regional compensation schemes.
Conclusions. In the light of persistently high occurrence of wolf–livestock conflict, and widespread illegal killing of wolves, we argue that compensation programs in Italy currently provide no evidence of being a functional and cost-effective conservation tool. However, lack of monitoring of compensation costs in Italy at all institutional levels, including non-government organisations (NGOs), reveals that compensation policies are not being evaluated, nor is their effectiveness being assessed.
Implications. We contend this is an unwise and unsustainable strategy to reduce the conflict, especially in the light of the recent increase in wolf numbers and, most importantly, a marked change in livestock husbandry practices. By emphasising the need for a thorough revision of the compensation schemes adopted for wolf conservation in Italy, we advocate new and theoretically sound solutions to current compensation policies.
Therapeutically targeting cyclin D1 in primary tumors arising from loss of
Ini1
Authors: Smith Melissa E. , Cimica Velasco , Chinni Srinivasa , Jana Suman , Koba Wade , Yang Zhixia , Fine Eugene , Zagzag David , Montagna Cristina , Kalpana Ganjam V.
Published: December 2010

Rhabdoid tumors (RTs) are rare, highly aggressive pediatric malignancies with poor prognosis and with no standard or effective treatment strategies. RTs are characterized by biallelic inactivation of the
INI1
tumor suppressor gene. INI1 directly represses
CCND1
and activates cyclin-dependent kinase (cdk) inhibitors p16
Ink4a
and p21
CIP
. RTs are exquisitely dependent on cyclin D1 for genesis and survival. To facilitate translation of unique therapeutic strategies, we have used genetically engineered,

Ini1
+/−

mice for therapeutic testing. We found that PET can be used to noninvasively and accurately detect primary tumors in

Ini1
+/−

mice. In a PET-guided longitudinal study, we found that treating

Ini1
+/−

mice bearing primary tumors with the pan-cdk inhibitor flavopiridol resulted in complete and stable regression of some tumors. Other tumors showed resistance to flavopiridol, and one of the resistant tumors overexpressed cyclin D1, more than flavopiridol-sensitive cells. The concentration of flavopiridol used was not sufficient to down-modulate the high level of cyclin D1 and failed to induce cell death in the resistant cells. Furthermore, FISH and PCR analyses indicated that there is aneuploidy and increased
CCND1
copy number in resistant cells. These studies indicate that resistance to flavopiridol may be correlated to elevated cyclin D1 levels. Our studies also indicate that

Ini1
+/−

mice are valuable tools for testing unique therapeutic strategies and for understanding mechanisms of drug resistance in tumors that arise owing to loss of
Ini1
, which is essential for developing effective treatment strategies against these aggressive tumors.
Parathyroid hormone/parathyroid hormone-related protein receptor signaling is required for maintenance of the growth plate in postnatal life
Authors: Hirai Takao , Chagin Andrei S. , Kobayashi Tatsuya , Mackem Susan , Kronenberg Henry M.
Published: December 2010

Parathyroid hormone (PTH)-related protein (PTHrP), regulated by Indian hedgehog and acting through the PTH/PTHrP receptor (PPR), is crucial for normal cartilage development. These observations suggest a possible role of PPR signaling in the postnatal growth plate; however, the role of PPR signaling in postnatal chondrocytes is unknown. In this study, we have generated tamoxifen-inducible and cartilage-specific PPR KO mice to evaluate the physiological role of PPR signaling in postnatal chondrocytes. We found that inactivation of the PPR in chondrocytes postnatally leads to accelerated differentiation of chondrocytes, followed by disappearance of the growth plate. We also observed an increase of TUNEL-positive cells and activities of caspase-3 and caspase-9 in the growth plate, along with a decrease in phosphorylation of Bad at Ser155 in postnatal PPR KO mice. Administration of a low-phosphate diet, which prevents apoptosis of chondrocytes, prevented the disappearance of the growth plate. Taken together, these observations suggest that the major consequences of PPR activation are similar in both the fetal and postnatal growth plates. Moreover, chondrocyte apoptosis through the activation of a mitochondrial pathway may be involved in the process of premature disappearance of the growth plate by postnatal inactivation of the PPR in chondrocytes.
Essential role for mast cell tryptase in acute experimental colitis
Authors: Hamilton Matthew J. , Sinnamon Mark J. , Lyng Gregory D. , Glickman Jonathan N. , Wang Xueli , Xing Wei , Krilis Steven A. , Blumberg Richard S. , Adachi Roberto , Lee David M. , Stevens Richard L.
Published: December 2010

Patients with inflammatory bowel disease (IBD) have increased numbers of human tryptase-β (hTryptase-β)-positive mast cells (MCs) in the gastrointestinal tract. The amino acid sequence of mouse mast cell protease (mMCP)-6 is most similar to that of hTryptase-β. We therefore hypothesized that this mMCP, or the related tryptase mMCP-7, might have a prominent proinflammatory role in experimental colitis. The dextran sodium sulfate (DSS) and trinitrobenzene sulfonic acid (TNBS) colitis models were used to evaluate the differences between C57BL/6 (B6) mouse lines that differ in their expression of mMCP-6 and mMCP-7 with regard to weight loss, colon histopathology, and endoscopy scores. Microarray analyses were performed, and confirmatory real-time PCR, ELISA, and/or immunohistochemical analyses were carried out on a number of differentially expressed cytokines, chemokines, and matrix metalloproteinases (MMPs). The mMCP-6–null mice that had been exposed to DSS had significantly less weight loss as well as significantly lower pathology and endoscopy scores than similarly treated mMCP-6–expressing mice. This difference in colitis severity was confirmed endoscopically in the TNBS-treated mice. Evaluation of the distal colon segments revealed that numerous proinflammatory cytokines, chemokines that preferentially attract neutrophils, and MMPs that participate in the remodeling of the ECM were all markedly increased in the colons of DSS-treated WT mice relative to untreated WT mice and DSS-treated mMCP-6–null mice. Collectively, our data show that mMCP-6 (but not mMCP-7) is an essential MC-restricted mediator in chemically induced colitis and that this tryptase acts upstream of many of the factors implicated in IBD.
Intrahost modeling of artemisinin resistance in
Plasmodium falciparum
Authors: Saralamba Sompob , Pan-Ngum Wirichada , Maude Richard J. , Lee Sue J. , Tarning Joel , Lindegårdh Niklas , Chotivanich Kesinee , Nosten François , Day Nicholas P. J. , Socheat Duong , White Nicholas J. , Dondorp Arjen M. , White Lisa J.
Published: December 2010

Artemisinin-resistant
Plasmodium falciparum
malaria has emerged in western Cambodia. Resistance is characterized by prolonged in vivo parasite clearance times (PCTs) following artesunate treatment. The biological basis is unclear. The hypothesis that delayed parasite clearance results from a stage-specific reduction in artemisinin sensitivity of the circulating young asexual parasite ring stages was examined. A mathematical model was developed, describing the intrahost parasite stage-specific pharmacokinetic–pharmacodynamic relationships. Model parameters were estimated using detailed pharmacokinetic and parasite clearance data from 39 patients with uncomplicated falciparum malaria treated with artesunate from Pailin (western Cambodia) where artemisinin resistance was evident and 40 patients from Wang Pha (northwestern Thailand) where efficacy was preserved. The mathematical model reproduced the observed parasite clearance for each patient with an accurate goodness of fit (rmsd: 0.03–0.67 in log
10
scale). The parameter sets that provided the best fits with the observed in vivo data consist of a highly conserved concentration–effect relationship for the trophozoite and schizont parasite stages, but a variable relationship for the ring stages. The model-derived assessment suggests that the efficacy of artesunate on ring stage parasites is reduced significantly in Pailin. This result supports the hypothesis that artemisinin resistance mainly reflects reduced ring-stage susceptibility and predicts that doubling the frequency of dosing will accelerate clearance of artemisinin-resistant parasites.
Nanodiamonds do not provide unique evidence for a Younger Dryas impact
Authors: Tian H. , Schryvers D. , Claeys Ph.
Published: December 2010

Microstructural,
δ
13
C isotope and C/N ratio investigations were conducted on excavated material from the black Younger Dryas boundary in Lommel, Belgium, aiming for a characterisation of the carbon content and structures. Cubic diamond nanoparticles are found in large numbers. The larger ones with diameters around or above 10 nm often exhibit single or multiple twins. The smaller ones around 5 nm in diameter are mostly defect-free. Also larger flake-like particles, around 100 nm in lateral dimension, with a cubic diamond structure are observed as well as large carbon onion structures. The combination of these characteristics does not yield unique evidence for an exogenic impact related to the investigated layer.
Z-DNA-forming silencer in the first exon regulates human ADAM-12 gene expression
Authors: Ray Bimal K. , Dhar Srijita , Shakya Arvind , Ray Alpana
Published: December 2010

Upregulation of ADAM-12, a novel member of the multifunctional ADAM family of proteins is linked to cancer, arthritis and cardiac hypertrophy. Basal expression of ADAM-12 is very low in adult tissues but rises markedly in response to certain physiological cues, such as during pregnancy in the placenta, during development in neonatal skeletal muscle and bone and in regenerating muscle. Studies on ADAM-12 regulation have identified a highly conserved negative regulatory element (NRE) at the 5′-UTR of human ADAM-12 gene, which acts as a transcriptional repressor. The NRE contains a stretch of dinucleotide-repeat sequence that is able to adopt a Z-DNA conformation both in vitro and in vivo and interacts with hZαADAR1, a bona fide Z-DNA-binding protein. Substitution of the dinucleotide-repeat-element with a non-Z-DNA-forming sequence inhibited NRE function. We have detected a NRE DNA-binding protein activity in several tissues where ADAM-12 expression is low while no such activity was seen in the placenta where ADAM-12 expression is high. These observations suggest that interaction of these proteins with ADAM-12 NRE is critical for transcriptional repression of ADAM-12. We also show that the Z-DNA forming transcriptional repressor element, by interacting with these putative Z-DNA-binding proteins, is involved in the maintenance of constitutive low-level expression of human ADAM-12. Together these results provide a foundation for therapeutic down-regulation of ADAM-12 in cancer, arthritis and cardiac hypertrophy.
Neural systems predicting long-term outcome in dyslexia
Authors: Hoeft Fumiko , McCandliss Bruce D. , Black Jessica M. , Gantman Alexander , Zakerani Nahal , Hulme Charles , Lyytinen Heikki , Whitfield-Gabrieli Susan , Glover Gary H. , Reiss Allan L. , Gabrieli John D. E.
Published: December 2010

Individuals with developmental dyslexia vary in their ability to improve reading skills, but the brain basis for improvement remains largely unknown. We performed a prospective, longitudinal study over 2.5 y in children with dyslexia (
n
= 25) or without dyslexia (
n
= 20) to discover whether initial behavioral or brain measures, including functional MRI (fMRI) and diffusion tensor imaging (DTI), can predict future long-term reading gains in dyslexia. No behavioral measure, including widely used and standardized reading and language tests, reliably predicted future reading gains in dyslexia. Greater right prefrontal activation during a reading task that demanded phonological awareness and right superior longitudinal fasciculus (including arcuate fasciculus) white-matter organization significantly predicted future reading gains in dyslexia. Multivariate pattern analysis (MVPA) of these two brain measures, using linear support vector machine (SVM) and cross-validation, predicted significantly above chance (72% accuracy) which particular child would or would not improve reading skills (behavioral measures were at chance). MVPA of whole-brain activation pattern during phonological processing predicted which children with dyslexia would improve reading skills 2.5 y later with >90% accuracy. These findings identify right prefrontal brain mechanisms that may be critical for reading improvement in dyslexia and that may differ from typical reading development. Brain measures that predict future behavioral outcomes (neuroprognosis) may be more accurate, in some cases, than available behavioral measures.
Critical role of PI3K signaling for NF-κB–dependent survival in a subset of activated B-cell–like diffuse large B-cell lymphoma cells
Authors: Kloo Bernhard , Nagel Daniel , Pfeifer Matthias , Grau Michael , Düwel Michael , Vincendeau Michelle , Dörken Bernd , Lenz Peter , Lenz Georg , Krappmann Daniel
Published: December 2010

The activated B-cell–like (ABC) subtype of diffuse large B-cell lymphoma (DLBCL) represents a very aggressive human lymphoma entity. Constitutive NF-κB activation caused by chronic active B-cell receptor (BCR) signaling is common feature of many ABC DLBCL cells; however, the pathways linking BCR signaling to the NF-κB prosurvival network are largely unknown. Here we report that constitutive activity of PI3K and the downstream kinase PDK1 are essential for the viability of two ABC DLBCL cell lines that carry mutations in the BCR proximal signaling adaptor CD79B. In these cells, PI3K inhibition reduces NF-κB activity and decreases the expression of NF-κB target genes. Furthermore, PI3K and PDK1 are required for maintaining MALT1 protease activity, which promotes survival of the affected ABC DLBCL cells. These results demonstrate a critical function of PI3K-PDK1 signaling upstream of MALT1 protease and NF-κB in distinct ABC DLBCL cells and provide a rationale for the pharmacologic use of PI3K inhibitors in DLBCL therapy.
Defects in succinate dehydrogenase in gastrointestinal stromal tumors lacking
KIT
and
PDGFRA
mutations
Authors: Janeway Katherine A. , Kim Su Young , Lodish Maya , Nosé Vânia , Rustin Pierre , Gaal José , Dahia Patricia L. M. , Liegl Bernadette , Ball Evan R. , Raygada Margarita , Lai Angela H. , Kelly Lorna , Hornick Jason L. ,   NIH Pediatric and Wild-Type GIST Clinic, O'Sullivan Maureen , de Krijger Ronald R. , Dinjens Winand N. M. , Demetri George D. , Antonescu Cristina R. , Fletcher Jonathan A. , Helman Lee , Stratakis Constantine A.
Published: December 2010

Carney-Stratakis syndrome, an inherited condition predisposing affected individuals to gastrointestinal stromal tumor (GIST) and paraganglioma, is caused by germline mutations in succinate dehydrogenase (SDH) subunits B, C, or D, leading to dysfunction of complex II of the electron transport chain. We evaluated the role of defective cellular respiration in sporadic GIST lacking mutations in
KIT
or
PDGFRA
(WT). Thirty-four patients with WT GIST without a personal or family history of paraganglioma were tested for
SDH
germline mutations. WT GISTs lacking demonstrable
SDH
genetic inactivation were evaluated for SDHB expression by immunohistochemistry and Western blotting and for complex II activity. For comparison, SDHB expression was also determined in
KIT
mutant and neurofibromatosis-1–associated GIST, and complex II activity was also measured in
SDH
-deficient paraganglioma and
KIT
mutant GIST; 4 of 34 patients (12%) with WT GIST without a personal or family history of paraganglioma had germline mutations in
SDHB
or
SDHC
. WT GISTs lacking somatic mutations or deletions in
SDH
subunits had either complete loss of or substantial reduction in SDHB protein expression, whereas most
KIT
mutant GISTs had strong SDHB expression. Complex II activity was substantially decreased in WT GISTs. WT GISTs, particularly those in younger patients, have defects in SDH mitochondrial complex II, and in a subset of these patients, GIST seems to arise from germline-inactivating
SDH
mutations. Testing for germline mutations in
SDH
is recommended in patients with WT GIST. These findings highlight a potential central role of SDH dysregulation in WT GIST oncogenesis.
Myogenic transcriptional activation of
MyoD
mediated by replication-independent histone deposition
Authors: Yang Jae-Hyun , Song Yunkyoung , Seol Ja-Hwan , Park Jin Young , Yang Yong-Jin , Han Jeung-Whan , Youn Hong-Duk , Cho Eun-Jung
Published: December 2010

In mammals, the canonical histone H3 and the variant H3.3 are assembled into chromatin through replication-coupled and replication-independent (RI) histone deposition pathways, respectively, to play distinct roles in chromatin function. H3.3 is largely associated with transcriptionally active regions via the activity of RI histone chaperone, HIRA. However, the precise role of the RI pathway and HIRA in active transcription and the mechanisms by which H3.3 affects gene activity are not known. In this study, we show that HIRA is an essential factor for muscle development by establishing
MyoD
activation in myotubes. HIRA and Asf1a, but not CHD1 or Asf1b, mediate H3.3 incorporation in the promoter and the critical upstream regulatory regions of the
MyoD
gene. HIRA and H3.3 are required for epigenetic transition into the more permissive chromatin structure for polymerase II recruitment to the promoter, regardless of transcription-associated covalent modification of histones. Our results suggest distinct epigenetic management of the master regulator with RI pathway components for cellular differentiation.
Vascular-mesenchymal cross-talk through Vegf and Pdgf drives organ patterning
Authors: Cool Jonah , DeFalco Tony J. , Capel Blanche
Published: December 2010

The initiation of de novo testis cord organization in the fetal gonad is poorly understood. Endothelial cell migration into XY gonads initiates testis morphogenesis. However, neither the signals that regulate vascularization of the gonad nor the mechanisms through which vessels affect tissue morphogenesis are known. Here, we show that Vegf signaling is required for gonad vascularization and cord morphogenesis. We establish that interstitial cells express
Vegfa
and respond, by proliferation, to endothelial migration. In the absence of vasculature, four-dimensional imaging of whole organs revealed that interstitial proliferation is reduced and prevents formation of wedge-like structures that partition the gonad into cord-forming domains. Antagonizing vessel maturation also reduced proliferation. However, proliferation of mesenchymal cells was rescued by the addition of PDGF-BB. These results suggest a pathway that integrates initiation of vascular development and testis cord morphogenesis, and lead to a model in which undifferentiated mesenchyme recruits blood vessels, proliferates in response, and performs a primary function in the morphogenesis and patterning of the developing organ.
Nitrous oxide emission from denitrification in stream and river networks
Authors: Beaulieu Jake J. , Tank Jennifer L. , Hamilton Stephen K. , Wollheim Wilfred M. , Hall Robert O. , Mulholland Patrick J. , Peterson Bruce J. , Ashkenas Linda R. , Cooper Lee W. , Dahm Clifford N. , Dodds Walter K. , Grimm Nancy B. , Johnson Sherri L. , McDowell William H. , Poole Geoffrey C. , Valett H. Maurice , Arango Clay P. , Bernot Melody J. , Burgin Amy J. , Crenshaw Chelsea L. , Helton Ashley M. , Johnson Laura T. , O'Brien Jonathan M. , Potter Jody D. , Sheibley Richard W. , Sobota Daniel J. , Thomas Suzanne M.
Published: December 2010

Nitrous oxide (N
2
O) is a potent greenhouse gas that contributes to climate change and stratospheric ozone destruction. Anthropogenic nitrogen (N) loading to river networks is a potentially important source of N
2
O via microbial denitrification that converts N to N
2
O and dinitrogen (N
2
). The fraction of denitrified N that escapes as N
2
O rather than N
2
(i.e., the N
2
O yield) is an important determinant of how much N
2
O is produced by river networks, but little is known about the N
2
O yield in flowing waters. Here, we present the results of whole-stream
15
N-tracer additions conducted in 72 headwater streams draining multiple land-use types across the United States. We found that stream denitrification produces N
2
O at rates that increase with stream water nitrate (NO
3
−
) concentrations, but that <1% of denitrified N is converted to N
2
O. Unlike some previous studies, we found no relationship between the N
2
O yield and stream water NO
3
−
. We suggest that increased stream NO
3
−
loading stimulates denitrification and concomitant N
2
O production, but does not increase the N
2
O yield. In our study, most streams were sources of N
2
O to the atmosphere and the highest emission rates were observed in streams draining urban basins. Using a global river network model, we estimate that microbial N transformations (e.g., denitrification and nitrification) convert at least 0.68 Tg·y
−1
of anthropogenic N inputs to N
2
O in river networks, equivalent to 10% of the global anthropogenic N
2
O emission rate. This estimate of stream and river N
2
O emissions is three times greater than estimated by the Intergovernmental Panel on Climate Change.
Genetic evidence for patrilocal mating behavior among Neandertal groups
Authors: Lalueza-Fox Carles , Rosas Antonio , Estalrrich Almudena , Gigli Elena , Campos Paula F. , García-Tabernero Antonio , García-Vargas Samuel , Sánchez-Quinto Federico , Ramírez Oscar , Civit Sergi , Bastir Markus , Huguet Rosa , Santamaría David , Gilbert M. Thomas P. , Willerslev Eske , de la Rasilla Marco
Published: December 2010

The remains of 12 Neandertal individuals have been found at the El Sidrón site (Asturias, Spain), consisting of six adults, three adolescents, two juveniles, and one infant. Archaeological, paleontological, and geological evidence indicates that these individuals represent all or part of a contemporaneous social group of Neandertals, who died at around the same time and later were buried together as a result of a collapse of an underground karst. We sequenced phylogenetically informative positions of mtDNA hypervariable regions 1 and 2 from each of the remains. Our results show that the 12 individuals stem from three different maternal lineages, accounting for seven, four, and one individual(s), respectively. Using a Y-chromosome assay to confirm the morphological determination of sex for each individual, we found that, although the three adult males carried the same mtDNA lineage, each of the three adult females carried different mtDNA lineages. These findings provide evidence to indicate that Neandertal groups not only were small and characterized by low genetic diversity but also were likely to have practiced patrilocal mating behavior.
Relative roles of climatic suitability and anthropogenic influence in determining the pattern of spread in a global invader
Authors: Roura-Pascual Núria , Hui Cang , Ikeda Takayoshi , Leday Gwénaël , Richardson David M. , Carpintero Soledad , Espadaler Xavier , Gómez Crisanto , Guénard Benoit , Hartley Stephen , Krushelnycky Paul , Lester Philip J. , McGeoch Melodie A. , Menke Sean B. , Pedersen Jes S. , Pitt Joel P. W. , Reyes Joaquin , Sanders Nathan J. , Suarez Andrew V. , Touyama Yoshifumi , Ward Darren , Ward Philip S. , Worner Sue P.
Published: December 2010

Because invasive species threaten the integrity of natural ecosystems, a major goal in ecology is to develop predictive models to determine which species may become widespread and where they may invade. Indeed, considerable progress has been made in understanding the factors that influence the local pattern of spread for specific invaders and the factors that are correlated with the number of introduced species that have become established in a given region. However, few studies have examined the relative importance of multiple drivers of invasion success for widespread species at global scales. Here, we use a dataset of >5,000 presence/absence records to examine the interplay between climatic suitability, biotic resistance by native taxa, human-aided dispersal, and human modification of habitats, in shaping the distribution of one of the world's most notorious invasive species, the Argentine ant (
Linepithema humile
). Climatic suitability and the extent of human modification of habitats are primarily responsible for the distribution of this global invader. However, we also found some evidence for biotic resistance by native communities. Somewhat surprisingly, and despite the often cited importance of propagule pressure as a crucial driver of invasions, metrics of the magnitude of international traded commodities among countries were not related to global distribution patterns. Together, our analyses on the global-scale distribution of this invasive species provide strong evidence for the interplay of biotic and abiotic determinants of spread and also highlight the challenges of limiting the spread and subsequent impact of highly invasive species.
Socioeconomic legacy yields an invasion debt
Authors: Essl Franz , Dullinger Stefan , Rabitsch Wolfgang , Hulme Philip E. , Hülber Karl , Jarošík Vojtěch , Kleinbauer Ingrid , Krausmann Fridolin , Kühn Ingolf , Nentwig Wolfgang , Vilà Montserrat , Genovesi Piero , Gherardi Francesca , Desprez-Loustau Marie-Laure , Roques Alain , Pyšek Petr
Published: December 2010

Globalization and economic growth are widely recognized as important drivers of biological invasions. Consequently, there is an increasing need for governments to address the role of international trade in their strategies to prevent species introductions. However, many of the most problematic alien species are not recent arrivals but were introduced several decades ago. Hence, current patterns of alien-species richness may better reflect historical rather than contemporary human activities, a phenomenon which might be called “invasion debt.” Here, we show that across 10 taxonomic groups (vascular plants, bryophytes, fungi, birds, mammals, reptiles, amphibians, fish, terrestrial insects, and aquatic invertebrates) in 28 European countries, current numbers of alien species established in the wild are indeed more closely related to indicators of socioeconomic activity from the year 1900 than to those from 2000, although the majority of species introductions occurred during the second half of the 20th century. The strength of the historical signal varies among taxonomic groups, with those possessing good capabilities for dispersal (birds, insects) more strongly associated with recent socioeconomic drivers. Nevertheless, our results suggest a considerable historical legacy for the majority of the taxa analyzed. The consequences of the current high levels of socioeconomic activity on the extent of biological invasions will thus probably not be completely realized until several decades into the future.
Regulation of GABAergic synapse formation and plasticity by GSK3β-dependent phosphorylation of gephyrin
Authors: Tyagarajan Shiva K. , Ghosh Himanish , Yévenes Gonzalo E. , Nikonenko Irina , Ebeling Claire , Schwerdel Cornelia , Sidler Corinne , Zeilhofer Hanns Ulrich , Gerrits Bertran , Muller Dominique , Fritschy Jean-Marc
Published: December 2010

Postsynaptic scaffolding proteins ensure efficient neurotransmission by anchoring receptors and signaling molecules in synapse-specific subcellular domains. In turn, posttranslational modifications of scaffolding proteins contribute to synaptic plasticity by remodeling the postsynaptic apparatus. Though these mechanisms are operant in glutamatergic synapses, little is known about regulation of GABAergic synapses, which mediate inhibitory transmission in the CNS. Here, we focused on gephyrin, the main scaffolding protein of GABAergic synapses. We identify a unique phosphorylation site in gephyrin, Ser270, targeted by glycogen synthase kinase 3β (GSK3β) to modulate GABAergic transmission. Abolishing Ser270 phosphorylation increased the density of gephyrin clusters and the frequency of miniature GABAergic postsynaptic currents in cultured hippocampal neurons. Enhanced, phosphorylation-dependent gephyrin clustering was also induced in vitro and in vivo with lithium chloride. Lithium is a GSK3β inhibitor used therapeutically as mood-stabilizing drug, which underscores the relevance of this posttranslational modification for synaptic plasticity. Conversely, we show that gephyrin availability for postsynaptic clustering is limited by Ca
2+
-dependent gephyrin cleavage by the cysteine protease calpain-1. Together, these findings identify gephyrin as synaptogenic molecule regulating GABAergic synaptic plasticity, likely contributing to the therapeutic action of lithium.
Evolving concepts of specificity in immune reactions
Authors: Eisen Herman N. , Chakraborty Arup K.
Published: December 2010

Our goal is to provide a perspective on current understanding of the origins of specificity in immune reactions, a topic that has intrigued scientists for over a century. A fundamental property of adaptive immune responses is the ability to discriminate among an immense variety of substances by means of antibodies (Abs) and Ab-like receptors on T lymphocytes [T-cell receptors (TCRs)], each able to bind a particular chemical structure [the antigen (Ag)] and not, or only weakly, similar alternatives. Evidence has long existed, however, and has grown, especially recently, that while exhibiting remarkable specificity, many individual Abs and TCRs can also bind a variety of very different ligands. How can Ag recognition by these receptors exercise the great specificity for which they are renowned and yet react with a variety of different ligands (degeneracy)? We critically consider the mechanistic bases for this specificity/degeneracy enigma and also compare and contrast Ag recognition by Abs and TCRs.
Mechanism of RNA stabilization and translational activation by a pentatricopeptide repeat protein
Authors: Prikryl Jana , Rojas Margarita , Schuster Gadi , Barkan Alice
Published: December 2010

Pentatricopeptide repeat (PPR) proteins comprise a large family of helical repeat proteins that bind RNA and modulate organellar RNA metabolism. The mechanisms underlying the functions attributed to PPR proteins are unknown. We describe in vitro studies of the maize protein PPR10 that clarify how PPR10 modulates the stability and translation of specific chloroplast mRNAs. We show that recombinant PPR10 bound to its native binding site in the chloroplast
atpI–atpH
intergenic region (
i
) blocks both 5′→3′ and 3′→ 5 exoribonucleases in vitro; (
ii
) is sufficient to define the native processed
atpH
mRNA 5′-terminus in conjunction with a generic 5′→3′ exoribonuclease; and (
iii
) remodels the structure of the
atpH
ribosome-binding site in a manner that can account for PPR10’s ability to enhance
atpH
translation. In addition, we show that the minimal PPR10-binding site spans 17 nt. We propose that the site-specific barrier and RNA remodeling activities of PPR10 are a consequence of its unusually long, high-affinity interface with single-stranded RNA, that this interface provides a functional mimic to bacterial small RNAs, and that analogous activities underlie many of the biological functions that have been attributed to PPR proteins.
Artificial gene amplification reveals an abundance of promiscuous resistance determinants in
Escherichia coli
Authors: Soo Valerie W. C. , Hanson-Manful Paulina , Patrick Wayne M.
Published: December 2010

Duplicated genes provide an important raw material for adaptive evolution. However, the relationship between gene duplication and the emergence of new biochemical functions is complicated, and it has been difficult to quantify the likelihood of evolving novelty in any systematic manner. Here, we describe a comprehensive search for artificially amplified genes that are able to impart new phenotypes on
Escherichia coli
, provided their expression is up-regulated. We used a high-throughput, library-on-library strategy to screen for resistance to antibiotics and toxins. Cells containing a complete
E. coli
ORF library were exposed to 237 toxin-containing environments. From 86 of these environments, we identified a total of 115 cases where overexpressed ORFs imparted improved growth. Of the overexpressed ORFs that we tested, most conferred small but reproducible increases in minimum inhibitory concentration (≤16-fold) for their corresponding antibiotics. In many cases, proteins were acting promiscuously to impart resistance. In the absence of toxins, most strains bore no fitness cost associated with ORF overexpression. Our results show that even the genome of a nonpathogenic bacterium harbors a substantial reservoir of resistance genes, which can be readily accessed through overexpression mutations. During the growth of a population under selection, these mutations are most likely to be gene amplifications. Therefore, our work provides validation and biochemical insight into the innovation, amplification, and divergence model of gene evolution under continuous selection [Bergthorsson U, Andersson DI, Roth JR (2007)
Proc Natl Acad Sci USA
104:17004–17009], and also illustrates the high frequency at which novel traits can evolve in bacterial populations.
Calcium-dependent activator protein for secretion 2 (CAPS2) promotes BDNF secretion and is critical for the development of GABAergic interneuron network
Authors: Shinoda Yo , Sadakata Tetsushi , Nakao Kazuhito , Katoh-Semba Ritsuko , Kinameri Emi , Furuya Asako , Yanagawa Yuchio , Hirase Hajime , Furuichi Teiichi
Published: December 2010

Calcium-dependent activator protein for secretion 2 (CAPS2) is a dense-core vesicle-associated protein that is involved in the secretion of BDNF. BDNF has a pivotal role in neuronal survival and development, including the development of inhibitory neurons and their circuits. However, how CAPS2 affects BDNF secretion and its biological significance in inhibitory neurons are largely unknown. Here we reveal the role of CAPS2 in the regulated secretion of BDNF and show the effect of CAPS2 on the development of hippocampal GABAergic systems. We show that CAPS2 is colocalized with BDNF, both synaptically and extrasynaptically in axons of hippocampal neurons. Overexpression of exogenous CAPS2 in hippocampal neurons of CAPS2-KO mice enhanced depolarization-induced BDNF exocytosis events in terms of kinetics, frequency, and amplitude. We also show that in the CAPS2-KO hippocampus, BDNF secretion is reduced, and GABAergic systems are impaired, including a decreased number of GABAergic neurons and their synapses, a decreased number of synaptic vesicles in inhibitory synapses, and a reduced frequency and amplitude of miniature inhibitory postsynaptic currents. Conversely, excitatory neurons in the CAPS2-KO hippocampus were largely unaffected with respect to field excitatory postsynaptic potentials, miniature excitatory postsynaptic currents, and synapse number and morphology. Moreover, CAPS2-KO mice exhibited several GABA system-associated deficits, including reduced late-phase long-term potentiation at CA3–CA1 synapses, decreased hippocampal theta oscillation frequency, and increased anxiety-like behavior. Collectively, these results suggest that CAPS2 promotes activity-dependent BDNF secretion during the postnatal period that is critical for the development of hippocampal GABAergic networks.
Mouse telomerase reverse transcriptase (mTert) expression marks slowly cycling intestinal stem cells
Authors: Montgomery Robert K. , Carlone Diana L. , Richmond Camilla A. , Farilla Loredana , Kranendonk Mariette E. G. , Henderson Daniel E. , Baffour-Awuah Nana Yaa , Ambruzs Dana M. , Fogli Laura K. , Algra Selma , Breault David T.
Published: December 2010

The intestinal epithelium is maintained by a population of rapidly cycling (
Lgr5
+
) intestinal stem cells (ISCs). It has been postulated, however, that slowly cycling ISCs must also be present in the intestine to protect the genome from accumulating deleterious mutations and to allow for a response to tissue injury. Here, we identify a subpopulation of slowly cycling ISCs marked by mouse telomerase reverse transcriptase (
mTert
) expression that can give rise to

Lgr5
+

cells.
mTert
-expressing cells distribute in a pattern along the crypt–villus axis similar to long-term label-retaining cells (LRCs) and are resistant to tissue injury. Lineage-tracing studies demonstrate that

mTert
+

cells give rise to all differentiated intestinal cell types, persist long term, and contribute to the regenerative response following injury. Consistent with other highly regenerative tissues, our results demonstrate that a slowly cycling stem cell population exists within the intestine.
Non-ATG–initiated translation directed by microsatellite expansions
Authors: Zu Tao , Gibbens Brian , Doty Noelle S. , Gomes-Pereira Mário , Huguet Aline , Stone Matthew D. , Margolis Jamie , Peterson Mark , Markowski Todd W. , Ingram Melissa A. C. , Nan Zhenhong , Forster Colleen , Low Walter C. , Schoser Benedikt , Somia Nikunj V. , Clark H. Brent , Schmechel Stephen , Bitterman Peter B. , Gourdon Geneviève , Swanson Maurice S. , Moseley Melinda , Ranum Laura P. W.
Published: December 2010

Trinucleotide expansions cause disease by both protein- and RNA-mediated mechanisms. Unexpectedly, we discovered that CAG expansion constructs express homopolymeric polyglutamine, polyalanine, and polyserine proteins in the absence of an ATG start codon. This repeat-associated non-ATG translation (RAN translation) occurs across long, hairpin-forming repeats in transfected cells or when expansion constructs are integrated into the genome in lentiviral-transduced cells and brains. Additionally, we show that RAN translation across human spinocerebellar ataxia type 8 (SCA8) and myotonic dystrophy type 1 (DM1) CAG expansion transcripts results in the accumulation of SCA8 polyalanine and DM1 polyglutamine expansion proteins in previously established SCA8 and DM1 mouse models and human tissue. These results have implications for understanding fundamental mechanisms of gene expression. Moreover, these toxic, unexpected, homopolymeric proteins now should be considered in pathogenic models of microsatellite disorders.
Adaptive divergence between incipient species of
Anopheles gambiae
increases resistance to
Plasmodium
Authors: White Bradley J. , Lawniczak Mara K. N. , Cheng Changde , Coulibaly Mamadou B. , Wilson Michael D. , Sagnon N'Fale , Costantini Carlo , Simard Frederic , Christophides George K. , Besansky Nora J.
Published: December 2010

The African malaria mosquito
Anopheles gambiae
is diversifying into ecotypes known as M and S forms. This process is thought to be promoted by adaptation to different larval habitats, but its genetic underpinnings remain elusive. To identify candidate targets of divergent natural selection in M and S, we performed genomewide scanning in paired population samples from Mali, followed by resequencing and genotyping from five locations in West, Central, and East Africa. Genome scans revealed a significant peak of M-S divergence on chromosome 3L, overlapping five known or suspected immune response genes. Resequencing implicated a selective target at or near the
TEP1
gene, whose complement C3-like product has antiparasitic and antibacterial activity. Sequencing and allele-specific genotyping showed that an allelic variant of
TEP1
has been swept to fixation in M samples from Mali and Burkina Faso and is spreading into neighboring Ghana, but is absent from M sampled in Cameroon, and from all sampled S populations. Sequence comparison demonstrates that this allele is related to, but distinct from,
TEP1
alleles of known resistance phenotype. Experimental parasite infections of advanced mosquito intercrosses demonstrated a strong association between this
TEP1
variant and resistance to both rodent malaria and the native human malaria parasite
Plasmodium falciparum
. Although malaria parasites may not be direct agents of pathogen-mediated selection at
TEP1
in nature—where larvae may be the more vulnerable life stage—the process of adaptive divergence between M and S has potential consequences for malaria transmission.