bluuebunny/crossref_metadata_2025_split huggingface dataset:
Estimating population structure from AFLP amplification intensity
Authors: FOLL MATTHIEU , FISCHER MARTIN C. , HECKEL GERALD , EXCOFFIER LAURENT 
Published: September 2010

AbstractIn the last decade, amplified fragment length polymorphisms (AFLPs) have become one of the most widely used molecular markers to study the genetic structure of natural populations. Most of the statistical methods available to study the genetic structure of populations using AFLPs consider these markers as dominant and are thus unable to distinguish between individuals being heterozygous or homozygous for the dominant allele. Some attempts have been made to treat AFLPs as codominant markers by using AFLP band intensities to infer the most likely genotype of each individual. These two approaches have some drawbacks, the former discarding potentially valuable information and the latter being sometimes unable to correctly assign genotypes to individuals. In this study, we propose an alternative likelihood‐based approach, which does not attempt at inferring the genotype of each individual, but rather incorporate the uncertainty about genotypes into a Bayesian framework leading to the estimation of population‐specificFISandFSTcoefficients. We show with simulations that the accuracy of our method is much higher than one using AFLP as dominant markers and is generally close to what would be obtained by using the same number of Single‐Nucleotide Polymorphism (SNP) markers. The method is applied to a data set of four populations of the common vole (Microtus arvalis) from Grisons in Switzerland, for which we obtained 562 polymorphic AFLP markers. Our approach is very general and has the potential to make AFLP markers as useful as SNP data for nonmodel species.
Ancient DNA sequences point to a large loss of mitochondrial genetic diversity in the saiga antelope (Saiga tatarica) since the Pleistocene
Authors: CAMPOS PAULA F. , KRISTENSEN TOMMY , ORLANDO LUDOVIC , SHER ANDREI , KHOLODOVA MARINA V. , GÖTHERSTRÖM ANDERS , HOFREITER MICHAEL , DRUCKER DOROTHÉE G. , KOSINTSEV PAVEL , TIKHONOV ALEXEI , BARYSHNIKOV GENNADY. F. , WILLERSLEV ESKE , GILBERT M. THOMAS P. 
Published: September 2010

AbstractPrior to the Holocene, the range of the saiga antelope (Saiga tatarica) spanned from France to the Northwest Territories of Canada. Although its distribution subsequently contracted to the steppes of Central Asia, historical records indicate that it remained extremely abundant until the end of the Soviet Union, after which its populations were reduced by over 95%. We have analysed the mitochondrial control region sequence variation of 27 ancient and 38 modern specimens, to assay how the species’ genetic diversity has changed since the Pleistocene. Phylogenetic analyses reveal the existence of two well‐supported, and clearly distinct, clades of saiga. The first, spanning a time range from >49 500 14C ybp to the present, comprises all the modern specimens and ancient samples from the Northern Urals, Middle Urals and Northeast Yakutia. The second clade is exclusive to the Northern Urals and includes samples dating from between 40 400 to 10 250 14C ybp. Current genetic diversity is much lower than that present during the Pleistocene, an observation that data modelling using serial coalescent indicates cannot be explained by genetic drift in a population of constant size. Approximate Bayesian Computation analyses show the observed data is more compatible with a drastic population size reduction (c. 66–77%) following either a demographic bottleneck in the course of the Holocene or late Pleistocene, or a geographic fragmentation (followed by local extinction of one subpopulation) at the Holocene/Pleistocene transition.
Comparative transcriptomics implicates mechanisms of evolved pollution tolerance in a killifish population
Authors: WHITEHEAD A. , TRIANT D. A. , CHAMPLIN D. , NACCI D. 
Published: September 2010

AbstractWild populations of the killifishFundulus heteroclitusresident in heavily contaminated North American Atlantic coast estuaries have recently and independently evolved dramatic, heritable, and adaptive pollution tolerance. We compared physiological and transcriptome responses to embryonic polychlorinated biphenyl (PCB) exposures between one tolerant population and a nearby sensitive population to gain insight into genomic, physiological and biochemical mechanisms of evolved tolerance in killifish, which are currently unknown. The PCB exposure concentrations at which developmental toxicity emerged, the range of developmental abnormalities exhibited, and global as well as specific gene expression patterns were profoundly different between populations. In the sensitive population, PCB exposures produced dramatic, dose‐dependent toxic effects, concurrent with the alterations in the expression of many genes. For example, PCB‐mediated cardiovascular system failure was associated with the altered expression of cardiomyocyte genes, consistent with sarcomere mis‐assembly. In contrast, genome‐wide expression was comparatively refractory to PCB induction in the tolerant population. Tolerance was associated with the global blockade of the aryl hydrocarbon receptor (AHR) signalling pathway, the key mediator of PCB toxicity, in contrast to the strong dose‐dependent up‐regulation of AHR pathway elements observed in the sensitive population. Altered regulation of signalling pathways that cross‐talk with AHR was implicated as one candidate mechanism for the adaptive AHR signalling repression and the pollution tolerance that it affords. In addition to revealing mechanisms of PCB toxicity and tolerance, this study demonstrates the value of comparative transcriptomics to explore molecular mechanisms of stress response and evolved adaptive differences among wild populations.
Ancient lakes revisited: from the ecology to the genetics of speciation
Authors: CRISTESCU MELANIA E. , ADAMOWICZ SARAH J. , VAILLANT JAMES J. , HAFFNER DOUGLAS G. 
Published: September 2010

AbstractExplosive speciation in ancient lakes has fascinated biologists for centuries and has inspired classical work on the tempo and modes of speciation. Considerable attention has been directed towards the extrinsic forces of speciation—the geological, geographical and ecological peculiarities of ancient lakes. Recently, there has been a resurgence of interest in the intrinsic nature of these radiations, the biological characteristics conducive to speciation. While new species are thought to arise mainly by the gradual enhancement of reproductive isolation among geographically isolated populations, ancient lakes provide little evidence for a predominant role of geography in speciation. Recent phylogenetic work provides strong evidence that multiple colonization waves were followed by parallel intralacustrine radiations that proceeded at relatively rapid rates despite long‐term gene flow through hybridization and introgression. Several studies suggest that hybridization itself might act as a key evolutionary mechanism by triggering major genomic reorganization/revolution and enabling the colonization of new ecological niches in ancient lakes. These studies propose that hybridization is not only of little impediment to diversification but could act as an important force in facilitating habitat transitions, promoting postcolonization adaptations and accelerating diversification. Emerging ecological genomic approaches are beginning to shed light on the long‐standing evolutionary dilemma of speciation in the face of gene flow. We propose an integrative programme for future studies on speciation in ancient lakes.
Next‐generation sequencing as a tool to study microbial evolution
Authors: BROCKHURST MICHAEL A. , COLEGRAVE NICK , ROZEN DANIEL E. 
Published: September 2010

AbstractThanks to their short generation times and large population sizes, microbes evolve rapidly. Evolutionary biologists have exploited this to observe evolution in real time. The falling costs of whole‐genome sequencing using next‐generation technologies now mean that it is realistic to use this as a tool to study this rapid microbial evolution both in the laboratory and in the wild. Such experiments are being used to accurately estimate the rates of mutation, reveal the genetic targets and dynamics of natural selection, uncover the correlation (or lack thereof) between genetic and phenotypic change, and provide data to test long‐standing evolutionary hypotheses. These advances have important implications for our understanding of the within‐ and between‐host evolution of microbial pathogens.
DNA topology of highly transcribed operons in Salmonella enterica serovar Typhimurium
Authors: Booker Betty M. , Deng Shuang , Higgins N. Patrick 
Published: September 2010

SummaryBacteria differ from eukaryotes by having the enzyme DNA gyrase, which catalyses the ATP‐dependent negative supercoiling of DNA. Negative supercoils are essential for condensing chromosomes into an interwound (plectonemic) and branched structure known as the nucleoid. Topo‐1 removes excess supercoiling in an ATP‐independent reaction and works with gyrase to establish a topological equilibrium where supercoils move within 10 kb domains bounded by stochastic barriers along the sequence. However, transcription changes the stochastic pattern by generating supercoil diffusion barriers near the sites of gene expression. Using supercoil‐dependent Tn3 and γδ resolution assays, we studied DNA topology upstream, downstream and across highly transcribed operons. Whenever two Res sites flanked efficiently transcribed genes, resolution was inhibited and the loss in recombination efficiency was proportional to transcription level. Ribosomal RNA operons have the highest transcription rates, and resolution assays at the rrnG and rrnH operons showed inhibitory levels 40–100 times those measured in low‐transcription zones. Yet, immediately upstream and downstream of RNA polymerase (RNAP) initiation and termination sites, supercoiling characteristics were similar to poorly transcribed zones. We present a model that explains why RNAP blocks plectonemic supercoil movement in the transcribed track and suggests how gyrase and TopA control upstream and downstream transcription‐driven supercoiling.
Non‐stop mRNA decay initiates at the ribosome
Authors: Ge Zhiyun , Mehta Preeti , Richards Jamie , Karzai A. Wali 
Published: September 2010

SummaryThe translation machinery deciphers genetic information encoded within mRNAs to synthesize proteins needed for various cellular functions. Defective mRNAs that lack in‐frame stop codons trigger non‐productive stalling of ribosomes. We investigated how cells deal with such defective mRNAs, and present evidence to demonstrate that RNase R, a processive 3′‐to‐5′ exoribonuclease, is recruited to stalled ribosomes for the specific task of degrading defective mRNAs. The recruitment process is selective for non‐stop mRNAs and is dependent on the activities of SmpB protein and tmRNA. Most intriguingly, our analysis reveals that a unique structural feature of RNase R, the C‐terminal lysine‐rich (K‐rich) domain, is required both for productive ribosome engagement and targeted non‐stop mRNA decay activities of the enzyme. These findings provide new insights into how a general RNase is recruited to the translation machinery and highlight a novel role for the ribosome as a platform for initiating non‐stop mRNA decay.
Partitioning of P1 plasmids by gradual distribution of the ATPase ParA
Authors: Hatano Toshiyuki , Niki Hironori 
Published: September 2010

SummaryRecently, it has been reported that prokaryotes also have a mitotic‐like apparatus in which polymerized fibres govern the bipolar movement of chromosomes and plasmids. Here, we show evidence that a non‐mitotic‐like apparatus that does not form polymerized filaments carries out plasmid partitioning. P1 ParA, which is a DNA‐binding ATPase protein, was found to be distributed through the whole nucleoid and formed a dense spot at the centre of the nucleoid. The fluorescent intensity of the ParA spot blinked, and then the spot gradually migrated from the midcell to a cell quarter position. Such distribution was not observed in anucleate cells, suggesting that the nucleoid could be a matrix for gradual distribution of ParA. Plasmid DNA constantly colocalized at the spot of ParA and migrated according to spot migration and separation. Thus, the gradient distribution of ParA determines the destination of partitioning plasmids and may direct plasmids to the cell quarters.
Enteropathogenic E. coli non‐LEE encoded effectors NleH1 and NleH2 attenuate NF‐κB activation
Authors: Royan Sandhya V. , Jones Rheinallt M. , Koutsouris Athanasia , Roxas Jennifer L. , Falzari Kanakeshwari , Weflen Andrew W. , Kim Amy , Bellmeyer Amy , Turner Jerrold R. , Neish Andrew S. , Rhee Ki‐Jong , Viswanathan V. K. , Hecht Gail A. 
Published: September 2010

SummaryEnteric bacterial pathogens have evolved sophisticated strategies to evade host immune defences. Some pathogens deliver anti‐inflammatory effector molecules into the host cell cytoplasm via a type III secretion system (T3SS). Enteropathogenic Escherichia coli (EPEC) inhibits inflammation by an undefined, T3SS‐dependent mechanism. Two proteins encoded outside of the EPEC locus of enterocyte effacement (LEE) pathogenicity island, non‐LEE‐encoded effector H1 (NleH1) and H2 (NleH2), display sequence similarity to Shigella flexneri OspG, which inhibits activation of the pro‐inflammatory transcription factor NF‐κB. We hypothesized that the anti‐inflammatory effects of EPEC were mediated by NleH1 and NleH2. In this study, we examined the effect of NleH1/H2 on the NF‐κB pathway. We show that NleH1/H2 are secreted via the T3SS and that transfection of cells with plasmids harbouring nleH1 or nleH2 decreased IKK‐β‐induced NF‐κB activity and attenuated TNF‐α‐induced degradation of phospho‐IκBα by preventing ubiquitination. Serum KC levels were higher in mice infected with ΔnleH1H2 than those infected with WT EPEC, indicating that NleH1/H2 dampen pro‐inflammatory cytokine expression. ΔnleH1H2 was cleared more rapidly than WT EPEC while complementation of ΔnleH1H2 with either NleH1 or NleH2 prolonged colonization. Together, these data show that NleH1 and NleH2 function to dampen host inflammation and facilitate EPEC colonization during pathogenesis.
Distinct functional roles of homologous Cu+ efflux ATPases in Pseudomonas aeruginosa
Authors: González‐Guerrero Manuel , Raimunda Daniel , Cheng Xin , Argüello José M. 
Published: September 2010

SummaryIn bacteria, most Cu+‐ATPases confer tolerance to Cu by driving cytoplasmic metal efflux. However, many bacterial genomes contain several genes coding for these enzymes suggesting alternative roles. Pseudomonas aeruginosa has two structurally similar Cu+‐ATPases, CopA1 and CopA2. Both proteins are essential for virulence. Expressed in response to high Cu, CopA1 maintains the cellular Cu quota and provides tolerance to this metal. CopA2 belongs to a subgroup of ATPases that are expressed in association with cytochrome oxidase subunits. Mutation of copA2 has no effect on Cu toxicity nor intracellular Cu levels; but it leads to higher H2O2 sensitivity and reduced cytochrome oxidase activity. Mutation of both genes does not exacerbate the phenotypes produced by single‐gene mutations. CopA1 does not complement the copA2 mutant strain and vice versa, even when promoter regions are exchanged. CopA1 but not CopA2 complements an Escherichia coli strain lacking the endogenous CopA. Nevertheless, transport assays show that both enzymes catalyse cytoplasmic Cu+ efflux into the periplasm, albeit CopA2 at a significantly lower rate. We hypothesize that their distinct cellular functions could be based on the intrinsic differences in transport kinetic or the likely requirement of periplasmic partner Cu‐chaperone proteins specific for each Cu+‐ATPase.
Double‐blind randomized trial of risperidone versus divalproex in pediatric bipolar disorder
Authors: Pavuluri Mani N , Henry David B , Findling Robert L , Parnes Stephanie , Carbray Julie A , Mohammed Tahseen , Janicak Philip G , Sweeney John A 
Published: September 2010

Pavuluri MN, Henry DB, Findling RL, Parnes S, Carbray JA, Mohammed T, Janicak PG, Sweeney JA. Double‐blind randomized trial of risperidone versus divalproex in pediatric bipolar disorder. Bipolar Disord 2010: 12: 593–605. © 2010 The Authors. Journal compilation © 2010 John Wiley & Sons A/S.Objective:  To determine the relative effects of risperidone and divalproex in pediatric mania.Methods:  This is a double‐blind, randomized, outpatient clinical trial with 66 children and adolescents (mean age = 10.9 ± 3.3 years; age range = 8–18 years) with mania who were randomly assigned to either risperidone (0.5–2 mg/day, n = 33) or divalproex (60–120 μg/mL, n = 33) for a six‐week period. Measures included the Young Mania Rating Scale (YMRS) and Child Depression Rating Scale‐Revised (CDRS‐R).Results:  Mixed‐effects regression models, with interaction between time and the active drug as predictors, found that the risperidone group had more rapid improvement than the divalproex group (p < 0.05), although final scores did not differ significantly between groups. Mixed models using only those subjects who completed the six‐week study found similar results. The response rate on YMRS was 78.1% for risperidone and 45.5% for divalproex (p < 0.01). The remission rate for risperidone was 62.5%, compared with 33.3% for divalproex (p < 0.05). Improvement on the CDRS‐R was significantly higher for the risperidone group relative to the divalproex group (p < 0.05). There were no significant differences between groups in safety, but subject retention was significantly higher at study endpoint in the risperidone group (p < 0.01). Dropout rate was 24% in the risperidone group and 48% in the divalproex group, with increased irritability being the most common reason for dropout in the latter. There was no significant weight gain in either group.Conclusion:  Results suggest that risperidone was associated with more rapid improvement and greater reduction in manic symptoms compared to divalproex. Although the results suggest that both drugs are safe, risperidone’s lower attrition rate and lower rate of adverse events may suggest better toleration. Clinical trials with larger samples are required to confirm these preliminary findings.
Family‐focused treatment for caregivers of patients with bipolar disorder
Authors: Perlick Deborah A , Miklowitz David J , Lopez Norma , Chou James , Kalvin Carla , Adzhiashvili Victoria , Aronson Andrew 
Published: September 2010

Perlick DA, Miklowitz DJ, Lopez N, Chou J, Kalvin C, Adzhiashvili V, Aronson A. Family‐focused treatment for caregivers of patients with bipolar disorder. Bipolar Disord 2010: 12: 627–637. © 2010 The Authors. Journal compilation © 2010 John Wiley & Sons A/S.Objectives:  Family members of patients with bipolar disorder experience high rates of subjective and objective burden which place them at risk for adverse physical health and mental health outcomes. We present preliminary efficacy data from a novel variation of Family Focused Treatment [Miklowitz DJ. Bipolar Disorder: A Family‐Focused Treatment Approach (2nd ed.). New York: The Guilford Press, 2008] that aimed to reduce symptoms of bipolar disorder by working with caregivers to enhance illness management skills and self‐care.Methods:  The primary family caregivers of 46 patients with bipolar I (n = 40) or II (n = 6) disorder, diagnosed by the Structured Clinical Interview for DSM‐IV Axis I Disorders, were assigned randomly to receive either: (i) a 12–15‐session family‐focused, cognitive‐behavioral intervention designed to provide the caregiver with skills for managing the relative’s illness, attaining self‐care goals, and reducing strain, depression, and health risk behavior [Family‐Focused Treatment‐Health Promoting Intervention (FFT‐HPI)]; or (ii) an 8‐ to 12‐session health education (HE) intervention delivered via videotapes. We assessed patients pre‐ and post‐treatment on levels of depression and mania and caregivers on levels of burden, health behavior, and coping.Results:  Randomization to FFT‐HPI was associated with significant decreases in caregiver depressive symptoms and health risk behavior. Greater reductions in depressive symptoms among patients were also observed in the FFT‐HPI group. Reduction in patients’ depression was partially mediated by reductions in caregivers’ depression levels. Decreases in caregivers’ depression were partially mediated by reductions in caregivers’ levels of avoidance coping.Conclusions:  Families coping with bipolar disorder may benefit from family interventions as a result of changes in the caregivers’ ability to manage stress and regulate their moods, even when the patient is not available for treatment.
Autoimmune diseases, bipolar disorder, and non‐affective psychosis
Authors: Eaton William W , Pedersen Marianne G , Nielsen Philip R , Mortensen Preben Bo 
Published: September 2010

Eaton WW, Pedersen MG, Nielsen PR, Mortensen PB. Autoimmune diseases, bipolar disorder, and non‐affective psychosis. Bipolar Disord 2010: 12: 638–646. © 2010 The Authors. Journal compilation © 2010 John Wiley & Sons A/S.Objective:  Clinic‐based studies of immune function, as well as comorbidity of autoimmune diseases, bipolar disorder, and schizophrenia, suggest a possible autoimmune etiology. Studies of non‐affective psychosis and schizophrenia suggest common etiologies. The objective was to determine the degree to which 30 different autoimmune diseases are antecedent risk factors for bipolar disorder, schizophrenia, and non‐affective psychosis.Methods:  A cohort of 3.57 million births in Denmark was linked to the Psychiatric Case Register and the National Hospital Register. There were 20,317 cases of schizophrenia, 39,076 cases of non‐affective psychosis, and 9,920 cases of bipolar disorder.Results:  As in prior studies, there was a range of autoimmune diseases which predicted raised risk of schizophrenia in individuals who had a history of autoimmune diseases, and also raised risk in persons whose first‐degree relatives had an onset of autoimmune disease prior to onset of schizophrenia in the case. These relationships also existed for the broader category of non‐affective psychosis. Only pernicious anemia in the family was associated with raised risk for bipolar disorder (relative risk: 1.7), suggesting a small role for genetic linkage. A history of Guillain‐Barré syndrome, Crohn’s disease, and autoimmune hepatitis in the individual was associated with raised risk of bipolar disorder.Conclusions:  The familial relationship of schizophrenia to a range of autoimmune diseases extends to non‐affective psychosis, but not to bipolar disorder. The data suggest that autoimmune processes precede onset of schizophrenia, but also non‐affective psychosis and bipolar disorder.