bluuebunny/crossref_metadata_2025 huggingface dataset:
tRNA-derived microRNA modulates proliferation and the DNA damage response and is down-regulated in B cell lymphoma
Authors: Maute Roy L. , Schneider Christof , Sumazin Pavel , Holmes Antony , Califano Andrea , Basso Katia , Dalla-Favera Riccardo
Published: January 2013

Sequencing studies from several model systems have suggested that diverse and abundant small RNAs may be derived from tRNA, but the function of these molecules remains undefined. Here, we demonstrate that one such tRNA-derived fragment, cloned from human mature B cells and designated CU1276, in fact possesses the functional characteristics of a microRNA, including a
DICER1
-dependent biogenesis, physical association with Argonaute proteins, and the ability to repress mRNA transcripts in a sequence-specific manner. Expression of CU1276 is abundant in normal germinal center B cells but absent in germinal center-derived lymphomas, suggesting a role in the pathogenesis of this disease. Furthermore, CU1276 represses endogenous
RPA1
, an essential gene involved in many aspects of DNA dynamics, and consequently, expression of this tRNA-derived microRNA in a lymphoma cell line suppresses proliferation and modulates the molecular response to DNA damage. These results establish that functionally active microRNAs can be derived from tRNA, thus defining a class of genetic entities with potentially important biological roles.
Structure of the Sgt2/Get5 complex provides insights into GET-mediated targeting of tail-anchored membrane proteins
Authors: Simon Aline C. , Simpson Peter J. , Goldstone Rachael M. , Krysztofinska Ewelina M. , Murray James W. , High Stephen , Isaacson Rivka L.
Published: January 2013

Small, glutamine-rich, tetratricopeptide repeat protein 2 (Sgt2) is the first known port of call for many newly synthesized tail-anchored (TA) proteins released from the ribosome and destined for the GET (Guided Entry of TA proteins) pathway. This leads them to the residential membrane of the endoplasmic reticulum via an alternative to the cotranslational, signal recognition particle-dependent mechanism that their topology denies them. In yeast, the first stage of the GET pathway involves Sgt2 passing TA proteins on to the Get4/Get5 complex through a direct interaction between the N-terminal (NT) domain of Sgt2 and the ubiquitin-like (UBL) domain of Get5. Here we characterize this interaction at a molecular level by solving both a solution structure of Sgt2_NT, which adopts a unique helical fold, and a crystal structure of the Get5_UBL. Furthermore, using reciprocal chemical shift perturbation data and experimental restraints, we solve a structure of the Sgt2_NT/Get5_UBL complex, validate it via site-directed mutagenesis, and empirically determine its stoichiometry using relaxation experiments and isothermal titration calorimetry. Taken together, these data provide detailed structural information about the interaction between two key players in the coordinated delivery of TA protein substrates into the GET pathway.
Bayesian computation via empirical likelihood
Authors: Mengersen Kerrie L. , Pudlo Pierre , Robert Christian P.
Published: January 2013

Approximate Bayesian computation has become an essential tool for the analysis of complex stochastic models when the likelihood function is numerically unavailable. However, the well-established statistical method of empirical likelihood provides another route to such settings that bypasses simulations from the model and the choices of the approximate Bayesian computation parameters (summary statistics, distance, tolerance), while being convergent in the number of observations. Furthermore, bypassing model simulations may lead to significant time savings in complex models, for instance those found in population genetics. The Bayesian computation with empirical likelihood algorithm we develop in this paper also provides an evaluation of its own performance through an associated effective sample size. The method is illustrated using several examples, including estimation of standard distributions, time series, and population genetics models.
Genomic basis for coral resilience to climate change
Authors: Barshis Daniel J. , Ladner Jason T. , Oliver Thomas A. , Seneca François O. , Traylor-Knowles Nikki , Palumbi Stephen R.
Published: January 2013

Recent advances in DNA-sequencing technologies now allow for in-depth characterization of the genomic stress responses of many organisms beyond model taxa. They are especially appropriate for organisms such as reef-building corals, for which dramatic declines in abundance are expected to worsen as anthropogenic climate change intensifies. Different corals differ substantially in physiological resilience to environmental stress, but the molecular mechanisms behind enhanced coral resilience remain unclear. Here, we compare transcriptome-wide gene expression (via RNA-Seq using Illumina sequencing) among conspecific thermally sensitive and thermally resilient corals to identify the molecular pathways contributing to coral resilience. Under simulated bleaching stress, sensitive and resilient corals change expression of hundreds of genes, but the resilient corals had higher expression under control conditions across 60 of these genes. These “frontloaded” transcripts were less up-regulated in resilient corals during heat stress and included thermal tolerance genes such as heat shock proteins and antioxidant enzymes, as well as a broad array of genes involved in apoptosis regulation, tumor suppression, innate immune response, and cell adhesion. We propose that constitutive frontloading enables an individual to maintain physiological resilience during frequently encountered environmental stress, an idea that has strong parallels in model systems such as yeast. Our study provides broad insight into the fundamental cellular processes responsible for enhanced stress tolerances that may enable some organisms to better persist into the future in an era of global climate change.
Plant invasions and extinction debts
Authors: Gilbert Benjamin , Levine Jonathan M.
Published: January 2013

Whether introduced species invasions pose a major threat to biodiversity is hotly debated. Much of this debate is fueled by recent findings that competition from introduced organisms has driven remarkably few plant species to extinction. Instead, native plant species in invaded ecosystems are often found in refugia: patchy, marginal habitats unsuitable to their nonnative competitors. However, whether the colonization and extinction dynamics of these refugia allow long-term native persistence is uncertain. Of particular concern is the possibility that invasive plants may induce an extinction debt in the native flora, where persistence over the short term masks deterministic extinction trajectories. We examined how invader impacts on landscape structure influence native plant persistence by combining recently developed quantitative techniques for evaluating metapopulation persistence with field measurements of an invaded plant community. We found that European grass invasion of an edaphically heterogeneous California landscape has greatly decreased the likelihood of the persistence of native metapopulations. It does so via two main pathways: (
i
) decreasing the size of native refugia, which reduces seed production and increases local extinction, and (
ii
) eroding the dispersal permeability of the matrix between refugia, which reduces their connectivity. Even when native plant extinction is the deterministic outcome of invasion, the time to extinction can be on the order of hundreds of years. We conclude that the relatively short time since invasion in many parts of the world is insufficient to observe the full impact of plant invasions on native biodiversity.
Voltage regulates adrenergic receptor function
Authors: Rinne Andreas , Birk Alexandra , Bünemann Moritz
Published: January 2013

The present study demonstrates that agonist-mediated activation of α2A adrenergic receptors (α
2A
AR) is voltage-dependent. By resolving the kinetics of conformational changes of α
2A
AR at defined membrane potentials, we show that negative membrane potentials in the physiological range promote agonist-mediated activation of α
2A
AR. We discovered that the conformational change of α
2A
AR by voltage is independent from receptor-G protein docking and regulates receptor signaling, including β-arrestin binding, activation of G proteins, and G protein-activated inwardly rectifying K
+
currents. Comparison of the dynamics of voltage-dependence of clonidine- vs. norepinephrine-activated receptors uncovers interesting mechanistic insights. For norepinephrine, the time course of voltage-dependent deactivation reflected the deactivation kinetics of the receptor after agonist withdrawal and was strongly attenuated at saturating concentrations. In contrast, clonidine-activated α
2A
AR were switched by voltage even under fully saturating concentrations, and the kinetics of this switch was notably faster than dissociation of clonidine from α
2A
AR, indicating voltage-dependent regulation of the efficacy. We conclude that adrenergic receptors exhibit a unique, agonist-dependent mechanism of voltage-sensitivity that modulates downstream receptor signaling.
Cyanobacterial conversion of carbon dioxide to 2,3-butanediol
Authors: Oliver John W. K. , Machado Iara M. P. , Yoneda Hisanari , Atsumi Shota
Published: January 2013

Conversion of CO
2
for the synthesis of chemicals by photosynthetic organisms is an attractive target for establishing independence from fossil reserves. However, synthetic pathway construction in cyanobacteria is still in its infancy compared with model fermentative organisms. Here we systematically developed the 2,3-butanediol (23BD) biosynthetic pathway in
Synechococcus elongatus
PCC7942 as a model system to establish design methods for efficient exogenous chemical production in cyanobacteria. We identified 23BD as a target chemical with low host toxicity, and designed an oxygen-insensitive, cofactor-matched biosynthetic pathway coupled with irreversible enzymatic steps to create a driving force toward the target. Production of 23BD from CO
2
reached 2.38 g/L, which is a significant increase for chemical production from exogenous pathways in cyanobacteria. This work demonstrates that developing strong design methods can continue to increase chemical production in cyanobacteria.
Function of Piwi, a nuclear Piwi/Argonaute protein, is independent of its slicer activity
Authors: Darricarrère Nicole , Liu Na , Watanabe Toshiaki , Lin Haifan
Published: January 2013

The Piwi protein subfamily is essential for Piwi-interacting RNA (piRNA) biogenesis, transposon silencing, and germ-line development, all of which have been proposed to require Piwi endonuclease activity, as validated for two cytoplasmic Piwi proteins in mice. However, recent evidence has led to questioning of the generality of this mechanism for the Piwi members that reside in the nucleus.
Drosophila
offers a distinct opportunity to study the function of nuclear Piwi proteins because, among three
Drosophila
Piwi proteins—called Piwi, Aubergine, and Argonaute 3—Piwi is the only member of this subfamily that is localized in the nucleus and expressed in both germ-line and somatic cells in the gonad, where it is responsible for piRNA biogenesis and regulatory functions essential for fertility. In this study, we demonstrate beyond doubt that the slicer activity of Piwi is not required for any known functions in vivo. We show that, in transgenic flies with the DDX catalytic triad of PIWI mutated, neither primary nor secondary piRNA biogenesis is detectably affected, transposons remain repressed, and fertility is normal. Our observations demonstrate that the mechanism of Piwi is independent of its in vitro endonuclease activity. Instead, it is consistent with the alternative mode of Piwi function as a molecule involved in the piRNA-directed guidance of epigenetic factors to chromatin.
HDAC3-selective inhibitor enhances extinction of cocaine-seeking behavior in a persistent manner
Authors: Malvaez Melissa , McQuown Susan C. , Rogge George A. , Astarabadi Mariam , Jacques Vincent , Carreiro Samantha , Rusche James R. , Wood Marcelo A.
Published: January 2013

Nonspecific histone deacetylase (HDAC) inhibition has been shown to facilitate the extinction of drug-seeking behavior in a manner resistant to reinstatement. A key open question is which specific HDAC is involved in the extinction of drug-seeking behavior. Using the selective HDAC3 inhibitor RGFP966, we investigated the role of HDAC3 in extinction and found that systemic treatment with RGFP966 facilitates extinction in mice in a manner resistant to reinstatement. We also investigated whether the facilitated extinction is related to the enhancement of extinction consolidation during extinction learning or to negative effects on performance or reconsolidation. These are key distinctions with regard to any compound being used to modulate extinction, because a more rapid decrease in a defined behavior is interpreted as facilitated extinction. Using an innovative combination of behavioral paradigms, we found that a single treatment of RGFP966 enhances extinction of a previously established cocaine-conditioned place preference, while simultaneously enhancing long-term object-location memory within subjects. During extinction consolidation, HDAC3 inhibition promotes a distinct pattern of histone acetylation linked to gene expression within the infralimbic cortex, hippocampus, and nucleus accumbens. Thus, the facilitated extinction of drug-seeking cannot be explained by adverse effects on performance. These results demonstrate that HDAC3 inhibition enhances the memory processes involved in extinction of drug-seeking behavior.
Spatial regulation of UBXD8 and p97/VCP controls ATGL-mediated lipid droplet turnover
Authors: Olzmann James A. , Richter Caleb M. , Kopito Ron R.
Published: January 2013

UBXD8 is a membrane-embedded recruitment factor for the p97/VCP segregase that has been previously linked to endoplasmic reticulum (ER)-associated degradation and to the control of triacylglycerol synthesis in the ER. UBXD8 also has been identified as a component of cytoplasmic lipid droplets (LDs), but neither the mechanisms that control its trafficking between the ER and LDs nor its functions in the latter organelle have been investigated previously. Here we report that association of UBXD8 with the ER-resident rhomboid pseudoprotease UBAC2 specifically restricts trafficking of UBXD8 to LDs, and that the steady-state partitioning of UBXD8 between the ER and LDs can be experimentally manipulated by controlling the relative expression of these two proteins. We exploit this interaction to show that UBXD8-mediated recruitment of p97/VCP to LDs increases LD size by inhibiting the activity of adipose triglyceride lipase (ATGL), the rate-limiting enzyme in triacylglycerol hydrolysis. Our findings show that UBXD8 binds directly to ATGL and promotes dissociation of its endogenous coactivator, CGI-58. These data indicate that UBXD8 and p97/VCP play central integrative roles in cellular energy homeostasis.
Macropredatory ichthyosaur from the Middle Triassic and the origin of modern trophic networks
Authors: Fröbisch Nadia B. , Fröbisch Jörg , Sander P. Martin , Schmitz Lars , Rieppel Olivier
Published: January 2013

The biotic recovery from Earth’s most severe extinction event at the Permian-Triassic boundary largely reestablished the preextinction structure of marine trophic networks, with marine reptiles assuming the predator roles. However, the highest trophic level of today's marine ecosystems, i.e., macropredatory tetrapods that forage on prey of similar size to their own, was thus far lacking in the Paleozoic and early Mesozoic. Here we report a top-tier tetrapod predator, a very large (>8.6 m) ichthyosaur from the early Middle Triassic (244 Ma), of Nevada. This ichthyosaur had a massive skull and large labiolingually flattened teeth with two cutting edges indicative of a macropredatory feeding style. Its presence documents the rapid evolution of modern marine ecosystems in the Triassic where the same level of complexity as observed in today’s marine ecosystems is reached within 8 My after the Permian-Triassic mass extinction and within 4 My of the time reptiles first invaded the sea. This find also indicates that the biotic recovery in the marine realm may have occurred faster compared with terrestrial ecosystems, where the first apex predators may not have evolved before the Carnian.
Legacy of a half century of Athabasca oil sands development recorded by lake ecosystems
Authors: Kurek Joshua , Kirk Jane L. , Muir Derek C. G. , Wang Xiaowa , Evans Marlene S. , Smol John P.
Published: January 2013

The absence of well-executed environmental monitoring in the Athabasca oil sands (Alberta, Canada) has necessitated the use of indirect approaches to determine background conditions of freshwater ecosystems before development of one of the Earth’s largest energy deposits. Here, we use highly resolved lake sediment records to provide ecological context to ∼50 y of oil sands development and other environmental changes affecting lake ecosystems in the region. We show that polycyclic aromatic hydrocarbons (PAHs) within lake sediments, particularly C1-C4–alkylated PAHs, increased significantly after development of the bitumen resource began, followed by significant increases in dibenzothiophenes. Total PAH fluxes in the modern sediments of our six study lakes, including one site ∼90 km northwest of the major development area, are now ∼2.5–23 times greater than ∼1960 levels. PAH ratios indicate temporal shifts from primarily wood combustion to petrogenic sources that coincide with greater oil sands development. Canadian interim sediment quality guidelines for PAHs have been exceeded since the mid-1980s at the most impacted site. A paleoecological assessment of
Daphnia
shows that this sentinel zooplankter has not yet been negatively impacted by decades of high atmospheric PAH deposition. Rather, coincident with increases in PAHs, climate-induced shifts in aquatic primary production related to warmer and drier conditions are the primary environmental drivers producing marked daphniid shifts after ∼1960 to 1970. Because of the striking increase in PAHs, elevated primary production, and zooplankton changes, these oil sands lake ecosystems have entered new ecological states completely distinct from those of previous centuries.
Membrane-integral pyrophosphatase subfamily capable of translocating both Na
+
and H
+
Authors: Luoto Heidi H. , Baykov Alexander A. , Lahti Reijo , Malinen Anssi M.
Published: January 2013

One of the strategies used by organisms to adapt to life under conditions of short energy supply is to use the by-product pyrophosphate to support cation gradients in membranes. Transport reactions are catalyzed by membrane-integral pyrophosphatases (PPases), which are classified into two homologous subfamilies: H
+
-transporting (found in prokaryotes, protists, and plants) and Na
+
-transporting (found in prokaryotes). Transport activities have been believed to require specific machinery for each ion, in accordance with the prevailing paradigm in membrane transport. However, experiments using a fluorescent pH probe and
22
Na
+
measurements in the current study revealed that five bacterial PPases expressed in
Escherichia coli
have the ability to simultaneously translocate H
+
and Na
+
into inverted membrane vesicles under physiological conditions. Consistent with data from phylogenetic analyses, our results support the existence of a third, dual-specificity bacterial Na
+
,H
+
-PPase subfamily, which apparently evolved from Na
+
-PPases. Interestingly, genes for Na
+
,H
+
-PPase have been found in the major microbes colonizing the human gastrointestinal tract. The Na
+
,H
+
-PPases require Na
+
for hydrolytic and transport activities and are further activated by K
+
. Based on ionophore effects, we conclude that the Na
+
and H
+
transport reactions are electrogenic and do not result from secondary antiport effects. Sequence comparisons further disclosed four Na
+
,H
+
-PPase signature residues located outside the ion conductance channel identified earlier in PPases using X-ray crystallography. Our results collectively support the emerging paradigm that both Na
+
and H
+
can be transported via the same mechanism, with switching between Na
+
and H
+
specificities requiring only subtle changes in the transporter structure.
Modulating the innate immune response by combinatorial engineering of endotoxin
Authors: Needham Brittany D. , Carroll Sean M. , Giles David K. , Georgiou George , Whiteley Marvin , Trent M. Stephen
Published: January 2013

Despite its highly inflammatory nature, LPS is a molecule with remarkable therapeutic potential. Lipid A is a glycolipid that serves as the hydrophobic anchor of LPS and constitutes a potent ligand of the Toll-like receptor (TLR)4/myeloid differentiation factor 2 receptor of the innate immune system. A less toxic mixture of monophosphorylated lipid A species (MPL) recently became the first new Food and Drug Administration-approved adjuvant in over 70 y. Whereas wild-type
Escherichia coli
LPS provokes strong inflammatory MyD88 (myeloid differentiation primary response gene 88)-mediated TLR4 signaling, MPL preferentially induces less inflammatory TRIF (TIR-domain–containing adaptor-inducing IFN-β)-mediated responses. Here, we developed a system for combinatorial structural diversification of
E. coli
lipid A, yielding a spectrum of bioactive variants that display distinct TLR4 agonist activities and cytokine induction. Mice immunized with engineered lipid A/antigen emulsions exhibited robust IgG titers, indicating the efficacy of these molecules as adjuvants. This approach demonstrates how combinatorial engineering of lipid A can be exploited to generate a spectrum of immunostimulatory molecules for vaccine and therapeutics development.
Hemagglutinin homologue from H17N10 bat influenza virus exhibits divergent receptor-binding and pH-dependent fusion activities
Authors: Zhu Xueyong , Yu Wenli , McBride Ryan , Li Yan , Chen Li-Mei , Donis Ruben O. , Tong Suxiang , Paulson James C. , Wilson Ian A.
Published: January 2013

Bat influenza virus H17N10 represents a distinct lineage of influenza A viruses with gene segments coding for proteins that are homologs of the surface antigens, hemagglutinin (HA) and neuraminidase (NA). Our recent study of the N10 NA homolog revealed an NA-like structure, but with a highly divergent putative active site exhibiting little or no NA activity, and provided strong motivation for performing equivalent structural and functional analyses of the H17 HA protein. The overall structure of the H17 HA homolog from A/little yellow-shouldered bat/Guatemala/060/2010 at 3.18 Å resolution is very similar to other influenza HAs, with a putative receptor-binding site containing some conserved aromatic residues that form the base of the sialic acid binding site. However, the rest of the H17 receptor-binding site differs substantially from the other HA subtypes, including substitution of other conserved residues associated with receptor binding. Significantly, electrostatic potential analyses reveal that this putative receptor-binding site is highly acidic, making it unfavorable to bind any negatively charged sialylated receptors, consistent with the recombinant H17 protein exhibiting no detectable binding to sialylated glycans. Furthermore, the fusion mechanism is also distinct; trypsin digestion with recombinant H17 protein, when exposed to pH 4.0, did not degrade the HA1 and HA2, in contrast to other HAs. These distinct structural features and functional differences suggest that the H17 HA behaves very differently compared with other influenza HAs.
Augmenting CNS glucocerebrosidase activity as a therapeutic strategy for parkinsonism and other Gaucher-related synucleinopathies
Authors: Sardi S. Pablo , Clarke Jennifer , Viel Catherine , Chan Monyrath , Tamsett Thomas J. , Treleaven Christopher M. , Bu Jie , Sweet Lindsay , Passini Marco A. , Dodge James C. , Yu W. Haung , Sidman Richard L. , Cheng Seng H. , Shihabuddin Lamya S.
Published: January 2013

Mutations of
GBA1
, the gene encoding glucocerebrosidase, represent a common genetic risk factor for developing the synucleinopathies Parkinson disease (PD) and dementia with Lewy bodies. PD patients with or without
GBA1
mutations also exhibit lower enzymatic levels of glucocerebrosidase in the central nervous system (CNS), suggesting a possible link between the enzyme and the development of the disease. Previously, we have shown that early treatment with glucocerebrosidase can modulate α-synuclein aggregation in a presymptomatic mouse model of Gaucher-related synucleinopathy (
Gba1

D409V/D409V

) and ameliorate the associated cognitive deficit. To probe this link further, we have now evaluated the efficacy of augmenting glucocerebrosidase activity in the CNS of symptomatic
Gba1

D409V/D409V

mice and in a transgenic mouse model overexpressing A53T α-synuclein. Adeno-associated virus-mediated expression of glucocerebrosidase in the CNS of symptomatic
Gba1

D409V/D409V

mice completely corrected the aberrant accumulation of the toxic lipid glucosylsphingosine and reduced the levels of ubiquitin, tau, and proteinase K-resistant α-synuclein aggregates. Importantly, hippocampal expression of glucocerebrosidase in
Gba1

D409V/D409V

mice (starting at 4 or 12 mo of age) also reversed their cognitive impairment when examined using a novel object recognition test. Correspondingly, overexpression of glucocerebrosidase in the CNS of A53T α-synuclein mice reduced the levels of soluble α-synuclein, suggesting that increasing the glycosidase activity can modulate α-synuclein processing and may modulate the progression of α-synucleinopathies. Hence, increasing glucocerebrosidase activity in the CNS represents a potential therapeutic strategy for
GBA1
-related and non-
GBA1
–associated synucleinopathies, including PD.
Role of the inflammasome in defense against venoms
Authors: Palm Noah W. , Medzhitov Ruslan
Published: January 2013

Venoms consist of a complex mixture of toxic components that are used by a variety of animal species for defense and predation. Envenomation of mammalian species leads to an acute inflammatory response and can lead to the development of IgE-dependent venom allergy. However, the mechanisms by which the innate immune system detects envenomation and initiates inflammatory and allergic responses to venoms remain largely unknown. Here we show that bee venom is detected by the NOD-like receptor family, pyrin domain-containing 3 inflammasome and can trigger activation of caspase-1 and the subsequent processing and unconventional secretion of the leaderless proinflammatory cytokine IL-1β in macrophages. Whereas activation of the inflammasome by bee venom induces a caspase-1–dependent inflammatory response, characterized by recruitment of neutrophils to the site or envenomation, the inflammasome is dispensable for the allergic response to bee venom. Finally, we find that caspase-1–deficient mice are more susceptible to the noxious effects of bee and snake venoms, suggesting that a caspase-1–dependent immune response can protect against the damaging effects of envenomation.
Calcium oscillations-coupled conversion of actin travelling waves to standing oscillations
Authors: Wu Min , Wu Xudong , De Camilli Pietro
Published: January 2013

Dynamic spatial patterns of signaling factors or macromolecular assemblies in the form of oscillations or traveling waves have emerged as important themes in cell physiology. Feedback mechanisms underlying these processes and their modulation by signaling events and reciprocal cross-talks remain poorly understood. Here we show that antigen stimulation of mast cells triggers cyclic changes in the concentration of actin regulatory proteins and actin in the cell cortex that can be manifested in either spatial pattern. Recruitment of FBP17 and active Cdc42 at the plasma membrane, leading to actin polymerization, are involved in both events, whereas calcium oscillations, which correlate with global fluctuations of plasma membrane PI(4,5)P
2
, are tightly linked to standing oscillations and counteract wave propagation. These findings demonstrate the occurrence of a calcium-independent oscillator that controls the collective dynamics of factors linking the actin cytoskeleton to the plasma membrane. Coupling between this oscillator and the one underlying global plasma membrane PI(4,5)P2 and calcium oscillations spatially regulates actin dynamics, revealing an unexpected pattern-rendering mechanism underlying plastic changes occurring in the cortical region of the cell.
The significance of ethnicity in the Estonian return migration policy of the early 1920s
Authors: Rohtmets Helen
Published: January 2013

In this article the Estonian return migration policy is analyzed from the perspective of the return migrants’ ethnicity. The time period of this study covers the most intensive phase of the state-organized return of emigrants to the newly established Republic of Estonia. The survey of attitudes of the Estonian authorities towards the return of emigrants with different ethnic backgrounds leads to the conclusions that the return of ethnic Estonians was preferred to the return of non-Estonians during the first years of Estonia's independence on both economic and political grounds. The political loyalty of non-Estonians was doubted in the administrative circles of Estonia which was especially the case with regard to the emigrants that had formerly belonged to the ruling power elites. The negative attitudes towards the return of non-Estonians were further aggravated by the crisis the Estonian economy was facing at that time. As a result, a parallel with the return migration policies of other new nation-states that emerged from the ruins of the Russian empire can be drawn.
State, identity, and the politics of music: Eurovision and nation-building in Azerbaijan
Authors: Ismayilov Murad
Published: January 2013

Albeit often — and fairly — degraded in the world of high culture as a populist and politicized representation of music, the Eurovision Song Contest (ESC) — by sheer virtue of the populist and politicized nature of its essence — stands among the most consequential cultural encounters to which post-independence Azerbaijan has been exposed, in that the extent to which Baku's victory in the ESC-2011 — and the further developments this victory has generated — can potentially impact on, and contribute to, the very process of nation-building and national identity formation, with which this post-Soviet Muslim-majority country is currently struggling, is unparalleled by any of the state's earlier encounters of the kind. This paper focuses on, and examines, four intimately related ways in which the ESC and Azerbaijan's successful involvement with the latter worked to interfere with the country's nation-building: as a dubious factor in the evolution of the Western sense of self among Azerbaijanis; as a unifying force within the structure of the country's rapidly maturing civil society; as a medium working to open up a channel through which Western popular cultural elements could interfere with the evolving dynamics of, and work to globalize, indeed de-endogenize, indigenous Azerbaijani culture, on one hand, and unify the discursive realm within which the country's cultural domain is to further evolve, on the other; and, finally, as an important element serving to decouple the evolving processes within the country's cultural domain from the unfolding dynamics of conflict settlement and hence conducive to the diversification of public discourse in Azerbaijan.
Economic Values and Regional Economic Impacts of Recreational Fisheries in Mississippi Reservoirs
Authors: Hutt Clifford P. , Hunt Kevin M. , Steffen Susan F. , Grado Stephen C. , Miranda L. E.
Published: January 2013

This study estimated the economic benefit of recreational fisheries on two trophy crappie Pomoxis spp. fisheries in Mississippi. We accomplished this by estimating economic impacts of angler expenditures and angler willingness-to-pay for fishing trips above current expenditures. Anglers spent 91,811 activity days on Sardis Reservoir in 2006 and 46,036 on Grenada Reservoir in 2007. The total economic impacts to the state were estimated at US$5.83 million on Sardis Reservoir and $2.15 million on Grenada Reservoir, supporting 75 and 51 full- and part-time jobs, respectively. Total consumer surplus was $5.57 million and $4.46 million on Sardis and Grenada reservoirs, respectively. Last, we used a model that predicted the effect of average spring water levels on total angling effort to estimate resulting changes in economic benefits. Spring angling effort and associated economic benefits peaked at intermediate water levels and declined at both low and high water levels. Future changes in precipitation patterns in the southeastern United States may require altering reservoir guide curves to maximize economic benefits associated with reservoir fisheries.

Received June 25, 2012; accepted October 3, 2012
Influences of Artificial Reefs on Juvenile Red Snapper along the Mississippi Gulf Coast
Authors: Brandt Jason R. , Jackson Donald C.
Published: January 2013

Red Snapper Lutjanus campechanus represent one of the more economically important fisheries in the northern Gulf of Mexico; as such, Red Snapper abundance has decreased dramatically in the past two decades. The use of artificial reefs could aid in the rehabilitation of Red Snapper stocks by providing refuge for juveniles and a place of foraging and recruitment. A study was initiated to determine the effectiveness of different artificial reef distribution patterns in attracting and sustaining juvenile Red Snapper in the northern Gulf of Mexico. Fish traps (0.97 m long; 0.64 m high; funnel mouth size = 175×115 mm) were used to collect Red Snapper (<406 mm TL) that were associated with pyramid-shaped artificial reef structures (3.7-m triangular base; 2.4-m height; 3.2 metric tons) to evaluate two reef distribution designs: (1) five closely spaced pyramid units (“clumped” pattern) and (2) five closely spaced pyramids plus two sets of two pyramids at 30.5, 61.0, or 91.5 m from the five pyramids (“outlier” pattern). In 26 sampling trips, 927 Red Snapper were captured. Catch per unit effort (number of fish/trap soak-hour) did not differ significantly among artificial reef patterns (P = 0.396). Red Snapper TLs differed significantly among patterns (P = 0.005), with the largest mean TL (235 mm; SE = 5.14) occurring at the outlier pattern with 61.0-m spacing. Results from this study indicate that reef spacing and horizontal extension are important factors to consider when designing an artificial reef program, especially those that target juvenile Red Snapper.

Received February 2, 2012; accepted September 26, 2012
Full and convex linear subcategories are incompressible
Authors: Cibils Claude , Redondo Maria Julia , Solotar Andrea
Published: January 2013

Consider the intrinsic fundamental groupà laGrothendieck of a linear category, introduced in our earlier papers using connected gradings. In this article we prove that any full convex subcategory is incompressible, in the sense that the group map between the corresponding fundamental groups is injective. We start by proving the functoriality of the intrinsic fundamental group with respect to full subcategories, based on the study of the restriction of connected gradings.
Small Farmers, NGOs, and a Walmart World: Welfare Effects of Supermarkets Operating in Nicaragua
Authors: Michelson Hope C.
Published: January 2013

Despite more than a decade of NGO and government activities promoting developing world farmer participation in high‐value agricultural markets, evidence regarding the household welfare effects of such initiatives is limited. This article analyzes the geographic placement of supermarket supply chains in Nicaragua between 2000 and 2008 and uses a difference‐in‐differences specification on measures of supplier and nonsupplier assets to estimate the welfare effects of small farmer participation. Though results indicate that selling to supermarkets increases household productive asset holdings, they also suggest that only farmers with advantageous endowments of geography and water are likely to participate.
Managing US Defense Acquisition
Authors: Alic John A.
Published: January 2013

Management in government differs fundamentally from private sector management, the more so in defense, which differs from other US government missions in that very large sums are spent on high-technology systems and equipment to meet the unknowable contingencies of an uncertain future. Because of technological complexity, the difficulties of program selection, contracting, and oversight exceed those in other parts of government. An underappreciated set of problems aggravates these difficulties, notably a lack of metrics for assessing the performance of military systems. In the absence of such metrics, and given the elastic meanings attached to national security, civilian officials have been unable to exercise effective oversight of defense acquisition, leaving discretionary choices by military leaders largely unchecked. For such reasons, common prescriptions for acquisition reform, such as adoption of “proven business practices,” are unrealistic. Meaningful reform would begin by increasing the influence of civilian officials over acquisition decisions and reducing that of the armed forces.
Plant P450s as versatile drivers for evolution of species-specific chemical diversity
Authors: Hamberger Björn , Bak Søren
Published: January 2013

The irreversible nature of reactions catalysed by P450s makes these enzymes landmarks in the evolution of plant metabolic pathways. Founding members of P450 families are often associated with general (i.e. primary) metabolic pathways, restricted to single copy or very few representatives, indicative of purifying selection. Recruitment of those and subsequent blooms into multi-member gene families generates genetic raw material for functional diversification, which is an inherent characteristic of specialized (i.e. secondary) metabolism. However, a growing number of highly specialized P450s from not only the CYP71 clan indicate substantial contribution of convergent and divergent evolution to the observed general and specialized metabolite diversity. We will discuss examples of how the genetic and functional diversification of plant P450s drives chemical diversity in light of plant evolution. Even though it is difficult to predict the function or substrate of a P450 based on sequence similarity, grouping with a family or subfamily in phylogenetic trees can indicate association with metabolism of particular classes of compounds. Examples will be given that focus on multi-member gene families of P450s involved in the metabolic routes of four classes of specialized metabolites: cyanogenic glucosides, glucosinolates, mono- to triterpenoids and phenylpropanoids.
Origins of P450 diversity
Authors: Sezutsu Hideki , Le Goff Gaëlle , Feyereisen René
Published: January 2013

The P450 enzymes maintain a conserved P450 fold despite a considerable variation in sequence. The P450 family even includes proteins that lack the single conserved cysteine and are therefore no longer haem-thiolate proteins. The mechanisms of successive gene duplications leading to large families in plants and animals are well established. Comparisons of P450CYPgene clusters in related species illustrate the rapid changes in CYPome sizes. Examples ofCYPcopy number variation with effects on fitness are emerging, and these provide an opportunity to study the proximal causes of duplication or pseudogenization. Birth and death models can explain the proliferation ofCYPgenes that is amply illustrated by the sequence of every new genome. Thus, the distribution of P450 diversity within the CYPome of plants and animals, a few families with many genes (P450 blooms) and many families with few genes, follows similar power laws in both groups. A closer look at some families with few genes shows that these, often single member families, are not stable during evolution. The enzymatic prowess of P450 may predispose them to switch back and forth between metabolism of critical structural or signal molecules and metabolism dedicated to environmental response.
Role of cytochrome P450s in insecticide resistance: impact on the control of mosquito-borne diseases and use of insecticides on Earth
Authors: David Jean-Philippe , Ismail Hanafy Mahmoud , Chandor-Proust Alexia , Paine Mark John Ingraham
Published: January 2013

The fight against diseases spread by mosquitoes and other insects has enormous environmental, economic and social consequences. Chemical insecticides remain the first line of defence but the control of diseases, especially malaria and dengue fever, is being increasingly undermined by insecticide resistance. Mosquitoes have a large repertoire of P450s (over 100 genes). By pinpointing the key enzymes associated with insecticide resistance we can begin to develop new tools to aid the implementation of control interventions and reduce their environmental impact on Earth. Recent technological advances are helping us to build a functional profile of the P450 determinants of insecticide metabolic resistance in mosquitoes. Alongside, the cross-responses of mosquito P450s to insecticides and pollutants are also being investigated. Such research will provide the means to produce diagnostic tools for early detection of P450s linked to resistance. It will also enable the design of new insecticides with optimized efficacy in different environments.
A world of cytochrome P450s
Authors: Nelson David R.
Published: January 2013

The world we live in is a biosphere influenced by all organisms who inhabit it. It is also an ecology of genes, with some having rather startling effects. The premise put forth in this issue is cytochrome P450 is a significant player in the world around us. Life and the Earth itself would be visibly different and diminished without cytochrome P450s. The contributions to this issue range from evolution on the billion year scale to the colour of roses, from Darwin to Rachel Carson; all as seen through the lens of cytochrome P450.
Microbial cytochromes P450: biodiversity and biotechnology. Where do cytochromes P450 come from, what do they do and what can they do for us?
Authors: Kelly Steven L. , Kelly Diane E.
Published: January 2013

The first eukaryote genome revealed three yeast cytochromes P450 (CYPs), hence the subsequent realization that some microbial fungal genomes encode these proteins in 1 per cent or more of all genes (greater than 100) has been surprising. They are unique biocatalysts undertaking a wide array of stereo- and regio-specific reactions and so hold promise in many applications. Based on ancestral activities that included 14α-demethylation during sterol biosynthesis, it is now seen that CYPs are part of the genes and metabolism of most eukaryotes. In contrast, Archaea and Eubacteria often do not contain CYPs, while those that do are frequently interesting as producers of natural products undertaking their oxidative tailoring. Apart from roles in primary and secondary metabolism, microbial CYPs are actual/potential targets of drugs/agrochemicals and CYP51 in sterol biosynthesis is exhibiting evolution to resistance in the clinic and the field. Other CYP applications include the first industrial biotransformation for corticosteroid production in the 1950s, the diversion into penicillin synthesis in early mutations in fungal strain improvement and bioremediation using bacteria and fungi. The vast untapped resource of orphan CYPs in numerous genomes is being probed and new methods for discovering function and for discovering desired activities are being investigated.
An integrative variant analysis pipeline for accurate genotype/haplotype inference in population NGS data
Authors: Wang Yi , Lu James , Yu Jin , Gibbs Richard A. , Yu Fuli
Published: January 2013

Next-generation sequencing is a powerful approach for discovering genetic variation. Sensitive variant calling and haplotype inference from population sequencing data remain challenging. We describe methods for high-quality discovery, genotyping, and phasing of SNPs for low-coverage (approximately 5×) sequencing of populations, implemented in a pipeline called SNPTools. Our pipeline contains several innovations that specifically address challenges caused by low-coverage population sequencing: (1) effective base depth (EBD), a nonparametric statistic that enables more accurate statistical modeling of sequencing data; (2) variance ratio scoring, a variance-based statistic that discovers polymorphic loci with high sensitivity and specificity; and (3) BAM-specific binomial mixture modeling (BBMM), a clustering algorithm that generates robust genotype likelihoods from heterogeneous sequencing data. Last, we develop an imputation engine that refines raw genotype likelihoods to produce high-quality phased genotypes/haplotypes. Designed for large population studies, SNPTools' input/output (I/O) and storage aware design leads to improved computing performance on large sequencing data sets. We apply SNPTools to the International 1000 Genomes Project (1000G) Phase 1 low-coverage data set and obtain genotyping accuracy comparable to that of SNP microarray.
OsTZF1, a CCCH-Tandem Zinc Finger Protein, Confers Delayed Senescence and Stress Tolerance in Rice by Regulating Stress-Related Genes
Authors: Jan Asad , Maruyama Kyonoshin , Todaka Daisuke , Kidokoro Satoshi , Abo Mitsuru , Yoshimura Etsuro , Shinozaki Kazuo , Nakashima Kazuo , Yamaguchi-Shinozaki Kazuko
Published: January 2013

OsTZF1 is a member of the CCCH-type zinc finger gene family in rice (Oryza sativa). Expression of OsTZF1 was induced by drought, high-salt stress, and hydrogen peroxide. OsTZF1 gene expression was also induced by abscisic acid, methyl jasmonate, and salicylic acid. Histochemical activity of β-glucuronidase in transgenic rice plants containing the promoter of OsTZF1 fused with β-glucuronidase was observed in callus, coleoptile, young leaf, and panicle tissues. Upon stress, OsTZF1-green fluorescent protein localization was observed in the cytoplasm and cytoplasmic foci. Transgenic rice plants overexpressing OsTZF1 driven by a maize (Zea mays) ubiquitin promoter (Ubi:OsTZF1-  OX [for overexpression]) exhibited delayed seed germination, growth retardation at the seedling stage, and delayed leaf senescence. RNA interference (RNAi) knocked-down plants (OsTZF1-RNAi) showed early seed germination, enhanced seedling growth, and early leaf senescence compared with controls. Ubi:OsTZF1-  OX plants showed improved tolerance to high-salt and drought stresses and vice versa for OsTZF1-  RNAi plants. Microarray analysis revealed that genes related to stress, reactive oxygen species homeostasis, and metal homeostasis were regulated in the Ubi:OsTZF1-  OX plants. RNA-binding assays indicated that OsTZF1 binds to U-rich regions in the 3′ untranslated region of messenger RNAs, suggesting that OsTZF1 might be associated with RNA metabolism of stress-responsive genes. OsTZF1 may serve as a useful biotechnological tool for the improvement of stress tolerance in various plants through the control of RNA metabolism of stress-responsive genes.