bluuebunny/crossref_metadata_2025 huggingface dataset:
Depressive Symptoms and Associated Clinical Characteristics in Outpatients Seeking Community-Based Treatment for Alcohol and Drug Problems
Authors: Sanchez Katherine , Walker Robrina , Campbell Aimee N. C. , Greer Tracy L. , Hu Mei-Chen , Grannemann Bruce D. , Nunes Edward V. , Trivedi Madhukar H.
Published: August 2014

Background

Comorbid psychiatric and substance use disorders are common and associated with poorer treatment engagement, retention, and outcomes. This study examines the presence of depressive symptoms and the demographic and clinical correlates in a diverse sample of substance abuse treatment seekers to better characterize patients with co-occurring depressive symptoms and substance use disorders and understand potential treatment needs.

Methods

Baseline data from a randomized clinical effectiveness trial of a computer-assisted, Web-delivered psychosocial intervention were analyzed. Participants ( N = 507) were recruited from 10 geographically diverse outpatient drug treatment programs. Assessments included the self-report Patient Health Questionnaire, and measures of coping strategies, social functioning, physical health status, and substance use.

Results

One fifth (21%; n = 106) of the sample screened positive for depression; those screening positive for depression were significantly more likely to screen positive for anxiety (66.9%) and posttraumatic stress disorder (PTSD; 42.9%). After controlling for anxiety and PTSD symptoms, presence of depressive symptoms remained significantly associated with fewer coping strategies ( P = .001), greater impairment in social adjustment ( P < .001), and poorer health status ( P < .001), but not to days of drug use in the last 90 days ( P = .14).

Conclusions

Depression is a clinically significant problem among substance abusers, and, in this study, patients who screened positive for depression were more likely to have co-occurring symptoms of anxiety and PTSD. Additionally, the presence of depressive symptoms was associated with fewer coping strategies and poorer social adjustment. Coping skills are a significant predictor of addiction outcomes, and it may be especially important to screen for and enhance coping among depressed patients. Evidence-based interventions that target coping skills and global functioning among substance abusers with depressive symptoms may be important adjuncts to usual treatment.
Detection of active transcription factor binding sites with the combination of DNase hypersensitivity and histone modifications
Authors: Gusmao Eduardo G. , Dieterich Christoph , Zenke Martin , Costa Ivan G.
Published: August 2014

Motivation: The identification of active transcriptional regulatory elements is crucial to understand regulatory networks driving cellular processes such as cell development and the onset of diseases. It has recently been shown that chromatin structure information, such as DNase I hypersensitivity (DHS) or histone modifications, significantly improves cell-specific predictions of transcription factor binding sites. However, no method has so far successfully combined both DHS and histone modification data to perform active binding site prediction.

Results: We propose here a method based on hidden Markov models to integrate DHS and histone modifications occupancy for the detection of open chromatin regions and active binding sites. We have created a framework that includes treatment of genomic signals, model training and genome-wide application. In a comparative analysis, our method obtained a good trade-off between sensitivity versus specificity and superior area under the curve statistics than competing methods. Moreover, our technique does not require further training or sequence information to generate binding location predictions. Therefore, the method can be easily applied on new cell types and allow flexible downstream analysis such as de novo motif finding.

Availability and implementation: Our framework is available as part of the Regulatory Genomics Toolbox. The software information and all benchmarking data are available at http://costalab.org/wp/dh-hmm .

Contact:  ivan.costa@rwth-aachen.de or eduardo.gusmao@rwth-aachen.de

Supplementary information:  Supplementary data are available at Bioinformatics online.
Bias correction for selecting the minimal-error classifier from many machine learning models
Authors: Ding Ying , Tang Shaowu , Liao Serena G. , Jia Jia , Oesterreich Steffi , Lin Yan , Tseng George C.
Published: August 2014

Motivation: Supervised machine learning is commonly applied in genomic research to construct a classifier from the training data that is generalizable to predict independent testing data. When test datasets are not available, cross-validation is commonly used to estimate the error rate. Many machine learning methods are available, and it is well known that no universally best method exists in general. It has been a common practice to apply many machine learning methods and report the method that produces the smallest cross-validation error rate. Theoretically, such a procedure produces a selection bias. Consequently, many clinical studies with moderate sample sizes (e.g. n = 30–60) risk reporting a falsely small cross-validation error rate that could not be validated later in independent cohorts.

Results: In this article, we illustrated the probabilistic framework of the problem and explored the statistical and asymptotic properties. We proposed a new bias correction method based on learning curve fitting by inverse power law (IPL) and compared it with three existing methods: nested cross-validation, weighted mean correction and Tibshirani-Tibshirani procedure. All methods were compared in simulation datasets, five moderate size real datasets and two large breast cancer datasets. The result showed that IPL outperforms the other methods in bias correction with smaller variance, and it has an additional advantage to extrapolate error estimates for larger sample sizes, a practical feature to recommend whether more samples should be recruited to improve the classifier and accuracy. An R package ‘MLbias’ and all source files are publicly available.

Availability and implementation: tsenglab.biostat.pitt.edu/software.htm.

Contact:  ctseng@pitt.edu

Supplementary information:  Supplementary data are available at Bioinformatics online.
Tibetan Plateau climate dynamics: recent research progress and outlook
Authors: Wu Guoxiong , Duan Anmin , Liu Yimin , Mao Jiangyu , Ren Rongcai , Bao Qing , He Bian , Liu Boqi , Hu Wenting
Published: August 2014

This paper reviews progress in the study of Tibetan Plateau (TP) climate dynamics over the past decade. Several theoretical frameworks, including thermal adaptation and the TP sensible heat (SH) driving air-pump, have been developed to identify the mechanisms responsible for the circulation anomaly produced by thermal forcing of the TP. Numerical simulations demonstrate that the thermal effects of large-scale orography, including the Tibetan and Iranian Plateaus (TIP), are crucial for the formation of the East Asian and South Asian summer monsoons (SASM) because the surface SH of the TIP is the major driver of the water vapor transport required for the genesis of the north branch of the SASM. The large-scale orography of the TP affects the Asian climate through thermal forcing in spring and summer, and mechanical forcing in winter. The TP forcing can also influence the Asian summer monsoon (ASM) onset over the Bay of Bengal (BOB) by enhancing the BOB warm pool at the surface and by modulating the South Asian High (SAH) in the upper troposphere. On intra-seasonal timescales, the TP thermal forcing significantly modulates spring rainfall in southern China and generates the biweekly oscillation of the SAH in summer. Despite climate warming, the atmospheric heat source over the TP, particularly the spring SH, exhibits a clear weakening trend from the 1980s to 2000s. This weakening of the spring SH contributed to the anomalous ‘dry in the north’ and ‘wet in the south’ rainfall pattern observed over East China. Also discussed are challenges to further understanding the mechanism of TP forcing on the multi-scale variability of the ASM.
Sensitivity and Specificity of Procalcitonin in Predicting Bacterial Infections in Patients With Renal Impairment
Authors: El-sayed Dena , Grotts Jonathan , Golgert William A. , Sugar Alan M.
Published: August 2014

Background.  It is unclear whether procalcitonin is an accurate predictor of bacterial infections in patients with renal impairment, although it is used as a biomarker for early diagnosis of sepsis. We determined the sensitivity, specificity, positive and negative predictive values, accuracy and best predictive value of procalcitonin for predicting bacterial infection in adult patients with severe renal impairment.

Methods.  Retrospective study at a single-center community teaching hospital involving 473 patients, ages 18–65, with Modification of Diet in Renal Disease eGFR ≤30 ml/min per 1.73 m2, admitted between January 2009 and June 2012, with 660 independent hospital visits. A positive or negative culture (blood or ide.jpegiable focus of infection) was paired to the highest procalcitonin result performed 48 hours before or after collecting the culture.

Results.  The sensitivity and specificity to predict bacterial infection, using a procalcitonin level threshold of 0.5 ng/mL, was 0.80 and 0.35 respectively. When isolating for presence of bacteremia, the sensitivity and specificity were 0.89 and 0.35 respectively. An equation adjusting for optimum thresholds of procalcitonin levels for predicting bacterial infection at different levels of eGFR had a sensitivity and specificity of 0.55 and 0.80 respectively.

Conclusions.  Procalcitonin is not a reliably sensitive or specific predictor of bacterial infection in patients with renal impairment when using a single threshold. Perhaps two thresholds should be employed, where below the lower threshold (i.e. 0.5 ng/mL) bacterial infection is unlikely with a sensitivity of 0.80, and above the higher threshold (i.e. 3.2 ng/mL) bacterial infection is very likely with a specificity of 0.75.
Novel Fidaxomicin Treatment Regimens for Patients With Multiple Clostridium difficile Infection Recurrences That Are Refractory to Standard Therapies
Authors: Soriano Melinda M. , Danziger Larry H. , Gerding Dale N. , Johnson Stuart
Published: August 2014

Reports of fidaxomicin treatment for patients with multiple recurrent Clostridium difficile infections ([mrCDI] ie, more than 2 CDI episodes) indicate symptomatic response to this agent, but 50% have subsequent mrCDI episodes. In an effort to improve outcomes in patients with mrCDI we used novel regimens of fidaxomicin based on strategies used with vancomycin. Of 8 patients who received a 10-day chaser of fidaxomicin given twice daily after a course of vancomycin, 3 (38%) experienced a subsequent recurrence. Two (18%) of 11 patients who completed a 14- to 33-day course of fidaxomicin in a tapering dose experienced a recurrence, both of whom received additional antibiotics before that recurrence. The median symptom-free interval (SFI) after fidaxomicin taper was greater than the median SFI after the most effective prior regimen for those patients (257 days [interquartile range, 280] vs 25 days [interquartile range, 30], respectively; P = .003). A fidaxomicin chaser or taper regimen may be effective in patients with mrCDI, but the number of patients treated is small, and randomized comparative data are not available.
Staphylococcus aureus Infections After Elective Cardiothoracic Surgery: Observations From an International Randomized Placebo-Controlled Trial of an Investigational S aureus Vaccine
Authors: Allen Keith B. , Fowler Vance G. , Gammie James S. , Hartzel Jonathan S. , Onorato Matthew T. , DiNubile Mark J. , Sobanjo-ter Meulen Ajoke
Published: August 2014

Background.  An unmet need to prevent Staphylococcus aureus (SA) infections after cardiothoracic surgery persists despite current practices. Cost-effective implementation of preventive strategies requires contemporary knowledge about modifiable risk factors.

Methods.  From 2007 to 2011, an international, double-blind, randomized placebo-controlled trial of a novel SA vaccine (V710) was conducted in 7664 adults scheduled for median sternotomy at 164 sites. We analyzed SA infections developing up to 360 days postoperatively in 3832 placebo recipients.

Results.  Coronary artery bypass grafting was performed in 80.8% (3096 of 3832) of placebo recipients. The overall incidence of any postoperative SA infection was 3.1% (120 of 3832). Invasive SA infections (including bacteremia and deep sternal-wound infections) developed in 1.0%. Methicillin-resistant SA (MRSA) accounted for 19% (23 of 120) of SA infections, with 57% (13 of 23) of the MRSA infections occurring in diabetic patients. All-cause mortality was 4.1% (153 of 3712) in patients without SA infection, 7.2% (7 of 97) in methicillin-susceptible SA (MSSA) infections, and 17.3% (4 of 23) in MRSA infections (P < .01). Staphylococcus aureus nasal carriage was detected preoperatively in 18.3% (701 of 3096) patients, including 1.6% colonized with MRSA. Postoperative SA infections occurred in 7.0% (49 of 701) of colonized patients versus 2.3% (71 of 3131) of patients without colonization (relative risk = 3.1 [95% confidence interval, 2.2–4.4]).

Conclusions.  In this large international cohort of patients undergoing cardiac surgery and observed prospectively, invasive postoperative SA infections occurred in 1% of adult patients despite modern perioperative management. The attributable mortality rates were 3% for MSSA and 13% for MRSA infections. Preoperative nasal colonization with SA increased the risk of postoperative infection threefold. The utility of strategies to reduce this incidence warrants continued investigation.
Fundamental phenomena of quantum mechanics explored with neutron interferometers
Authors: Klepp Jürgen , Sponar Stephan , Hasegawa Yuji
Published: August 2014

Ongoing fascination with quantum mechanics keeps driving the development of the wide field of quantum optics, including its neutron optics branch. Application of neutron-optical methods and, in particular, neutron interferometry and polarimetry has a long-standing tradition for experimental investigations of fundamental quantum phenomena. We give an overview of related experimental efforts made in recent years.
Brain Neuroplastic Changes Accompany Anxiety and Memory Deficits in a Model of Complex Regional Pain Syndrome
Authors: Tajerian Maral , Leu David , Zou Yani , Sahbaie Peyman , Li Wenwu , Khan Hamda , Hsu Vivian , Kingery Wade , Huang Ting Ting , Becerra Lino , Clark J. David
Published: August 2014

Background:

Complex regional pain syndrome (CRPS) is a painful condition with approximately 50,000 annual new cases in the United States. It is a major cause of work-related disability, chronic pain after limb fractures, and persistent pain after extremity surgery. Additionally, CRPS patients often experience cognitive changes, anxiety, and depression. The supraspinal mechanisms linked to these CRPS-related comorbidities remain poorly understood.

Methods:

The authors used a previously characterized mouse model of tibia fracture/cast immobilization showing the principal stigmata of CRPS (n = 8 to 20 per group) observed in humans. The central hypothesis was that fracture/cast mice manifest changes in measures of thigmotaxis (indicative of anxiety) and working memory reflected in neuroplastic changes in amygdala, perirhinal cortex, and hippocampus.

Results:

The authors demonstrate that nociceptive sensitization in these mice is accompanied by altered thigmotactic behaviors in the zero maze but not open field assay, and working memory dysfunction in novel object recognition and social memory but not in novel location recognition. Furthermore, the authors found evidence of structural changes and synaptic plasticity including changes in dendritic architecture and decreased levels of synaptophysin and brain-derived neurotrophic factor in specific brain regions.

Conclusions:

The study findings provide novel observations regarding behavioral changes and brain plasticity in a mouse model of CRPS. In addition to elucidating some of the supraspinal correlates of the syndrome, this work supports the potential use of therapeutic interventions that not only directly target sensory input and other peripheral mechanisms, but also attempt to ameliorate the broader pain experience by modifying its associated cognitive and emotional comorbidities.
Hearing and seeing meaning in speech and gesture: insights from brain and behaviour
Authors: Özyürek Aslı
Published: August 2014

As we speak, we use not only the arbitrary form–meaning mappings of the speech channel but also motivated form–meaning correspondences, i.e. iconic gestures that accompany speech (e.g. inverted V-shaped hand wiggling across gesture space to demonstrate walking). This article reviews what we know about processing of semantic information from speech and iconic gestures in spoken languages during comprehension of such composite utterances. Several studies have shown that comprehension of iconic gestures involves brain activations known to be involved in semantic processing of speech: i.e. modulation of the electrophysiological recording component N400, which is sensitive to the ease of semantic integration of a word to previous context, and recruitment of the left-lateralized frontal–posterior temporal network (left inferior frontal gyrus (IFG), medial temporal gyrus (MTG) and superior temporal gyrus/sulcus (STG/S)). Furthermore, we integrate the information coming from both channels recruiting brain areas such as left IFG, posterior superior temporal sulcus (STS)/MTG and even motor cortex. Finally, this integration is flexible: the temporal synchrony between the iconic gesture and the speech segment, as well as the perceived communicative intent of the speaker, modulate the integration process. Whether these findings arespecialto gestures or are shared with actions or other visual accompaniments to speech (e.g. lips) or other visual symbols such as pictures are discussed, as well as the implications for a multimodal view of language.
Origin of symbol-using systems: speech, but not sign, without the semantic urge
Authors: Sereno Martin I.
Published: August 2014

Natural language—spoken and signed—is a multichannel phenomenon, involving facial and body expression, and voice and visual intonation that is often used in the service of a social urge to communicate meaning. Given that iconicity seems easier and less abstract than making arbitrary connections between sound and meaning, iconicity and gesture have often been invoked in the origin of language alongside the urge to convey meaning. To get a fresh perspective, we critically distinguish theoriginof a system capable of evolution from the subsequentevolutionthat system becomes capable of. Human language arose on a substrate of a system already capable of Darwinian evolution; the genetically supported uniquely human ability to learn a language reflects a key contact point between Darwinian evolution and language. Though implemented in brains generated by DNA symbols coding for protein meaning, the second higher-level symbol-using system of language now operates in a world mostly decoupled from Darwinian evolutionary constraints. Examination of Darwinian evolution of vocal learning in other animals suggests that the initial fixation of a key prerequisite to language into the human genome may actually have required initiallyside-steppingnot only iconicity, but the urge to mean itself. If sign languages came later, they would not have faced this constraint.
Neptunomonas acidivorans sp. nov., isolated from sediment, and emended description of the genus Neptunomonas
Authors: Yang Sung-Hyun , Seo Hyun-Seok , Lee Jung-Hyun , Kim Sang-Jin , Kwon Kae Kyoung
Published: August 2014

A Gram-reaction-negative, aerobic, rod-shaped (1.2–1.6 µm×0.6–0.8 µm), flagellated and motile marine bacterium, designated MEBiC06243T, was isolated from a sediment collected at Daebu Island in the Yellow Sea (37° 20′ N 126° 41′ E), Korea. The 16S rRNA gene sequence analysis revealed that strain MEBiC06243Tshowed high similarity withNeptunomonas naphthovoransNAG-2N-126T(96.3 %). Growth was observed at 10–39 °C (optimum 29 °C), at pH 6.0–9.0 (optimum pH 7) and with 0–7 % (optimum 2.5 %) NaCl. The predominant cellular fatty acids were C10 : 03-OH (6.1 %), C12 : 0(5.8 %), C16 : 0(30.5 %), C18 : 1ω7c(21.6 %) and summed feature 3 (comprising C15 : 02-OH and/or C16 : 1ω7c; 30.7 %). The DNA G+C content was 41.4 mol%. The major respiratory quinone was Q-8. Phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol, two unidentified lipids, one unidentified aminophospholipid and three unidentified aminolipids were detected as major polar lipids. On the basis of this polyphasic taxonomic data, strain MEBiC06243Tshould be classified as a novel species of the genusNeptunomonasproposed asNeptunomonas acidivoranssp. nov. The type strain is MEBiC06243T( = KCCM 42975T = JCM 18291T). An emended description of the genusNeptunomonasis also given.
Thalassotalea ponticola sp. nov., isolated from seawater, reclassification of Thalassomonas fusca as Thalassotalea fusca comb. nov. and emended description of the genus Thalassotalea
Authors: Park Sooyeon , Jung Yong-Taek , Kang Chul-Hyung , Park Ja-Min , Yoon Jung-Hoon
Published: August 2014

A Gram-stain-negative, aerobic, non-flagellated and rod-shaped or ovoid bacterial strain, designated GJSW-36T, was isolated from seawater at Geoje island in the South Sea, South Korea. Strain GJSW-36T grew optimally at pH 7.0–8.0, at 25 °C and in the presence of 2 % (w/v) NaCl. A neighbour-joining phylogenetic tree based on 16S rRNA gene sequences showed that strain GJSW-36T fell within the clade comprising the type strains of species of the genus

Thalassotalea

and

Thalassomonas fusca

. Strain GJSW-36T exhibited 16S rRNA gene sequence similarity values of 94.2–96.0 % to the type strains of species of the genus

Thalassotalea

and

Thalassomonas fusca

and of 93.8–94.5 % to the type strains of the other species of the genus

Thalassomonas

. Strain GJSW-36T contained ubiquinone-8 (Q-8) as the predominant ubiquinone and summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c), C17 : 1ω8c and C16 : 0 as the major fatty acids. The major polar lipids of strain GJSW-36T were phosphatidylglycerol and phosphatidylethanolamine. The DNA G+C content of strain GJSW-36T was 45.1 mol%. Differential phenotypic properties, together with the phylogenetic distinctiveness, demonstrated that strain GJSW-36T is separated from species of the genus

Thalassotalea

and

Thalassomonas fusca

. On the basis of the data presented, strain GJSW-36T is considered to represent a novel species of the genus

Thalassotalea

, for which the name Thalassotalea ponticola sp. nov. is proposed. The type strain is GJSW-36T ( = KCTC 42155T = CECT 8656T). From this study, it is also proposed that

Thalassomonas fusca

should be reclassified as a member of the genus

Thalassotalea

and the description of the genus

Thalassotalea

is emended.
Interaction of the carbon monoxide-releasing molecule Ru(CO)3Cl(glycinate) (CORM-3) with Salmonella enterica serovar Typhimurium: in situ measurements of carbon monoxide binding by integrating cavity dual-beam spectrophotometry
Authors: Rana Namrata , McLean Samantha , Mann Brian E. , Poole Robert K.
Published: August 2014

Carbon monoxide (CO) is a toxic gas that binds to haems, but also plays critical signalling and cytoprotective roles in mammalian systems; despite problems associated with systemic delivery by inhalation of the gas, it may be employed therapeutically. CO delivered to cells and tissues by CO-releasing molecules (CO-RMs) has beneficial and toxic effects not mimicked by CO gas; CO-RMs are also attractive candidates as novel antimicrobial agents. Salmonella enterica serovar Typhimurium is an enteropathogen causing gastroenteritis in humans. Recent studies have implicated haem oxygenase-1 (HO-1), the protein that catalyses the degradation of haem into biliverdin, free iron and CO, in the host immune response to Salmonella infection. In several studies, CO administration via CO-RMs elicited many of the protective roles of HO-1 induction and so we investigated the effects of a well-characterized water-soluble CO-RM, Ru(CO)3Cl(glycinate) (CORM-3), on Salmonella. CORM-3 exhibits toxic effects at concentrations significantly lower than those reported to cause toxicity to RAW 264.7 macrophages. We demonstrated here, through oxyhaemoglobin assays, that CORM-3 did not release CO spontaneously in phosphate buffer, buffered minimal medium or very rich medium. CORM-3 was, however, accumulated to high levels intracellularly (as shown by inductively coupled plasma MS) and released CO inside cells. Using growing Salmonella cultures without prior concentration, we showed for the first time that sensitive dual-beam integrating cavity absorption spectrophotometry can detect directly the CO released from CORM-3 binding in real-time to haems of the bacterial electron transport chain. The toxic effects of CO-RMs suggested potential applications as adjuvants to antibiotics in antimicrobial therapy.
Hsp90 promotes kinase evolution
Authors: Lachowiec Jennifer , Lemus Tzitziki , Borenstein Elhanan , Queitsch Christine
Published: August 2014

Heat-shock protein 90 (Hsp90) promotes the maturation and stability of its client proteins, including many kinases. In doing so, Hsp90 may allow its clients to accumulate mutations as previously proposed by the capacitor hypothesis. If true, Hsp90 clients should show increased evolutionary rate compared to non-clients; however, other factors, such as gene expression and protein connectivity, may confound or obscure the chaperone’s putative contribution. Here, we compared the evolutionary rates of many Hsp90 clients and non-clients in the human protein kinase superfamily. We show that Hsp90 client status promotes evolutionary rate independently of, but in a small magnitude similar to that of gene expression and protein connectivity. Hsp90’s effect on kinase evolutionary rate was detected across mammals, specifically relaxing purifying selection. Hsp90 clients also showed increased nucleotide diversity and harbored more damaging variation than non-client kinases across humans. These results are consistent with the central argument of the capacitor hypothesis that interaction with the chaperone allows its clients to harbor genetic variation. Hsp90 client status is thought to be highly dynamic with as few as one amino acid change rendering a protein dependent on the chaperone. Contrary to this expectation, we found that across protein kinase phylogeny Hsp90 client status tends to be gained, maintained, and shared among closely related kinases. We also infer that the ancestral protein kinase was not an Hsp90 client. Taken together, our results suggest that Hsp90 played an important role in shaping the kinase superfamily.
UniqTag: Content-derived unique and stable identifiers for gene annotation
Authors: Jackman Shaun D , Bohlmann Joerg , Birol Inanc
Published: August 2014

When working on an ongoing genome sequencing and assembly project, it is rather inconvenient when gene identifiers change from one build of the assembly to the next. The gene labelling system described here, UniqTag, addresses this common challenge. UniqTag assigns a unique identifier to each gene that is a representative k-mer, a string of length k, selected from the sequence of that gene. Unlike serial numbers, these identifiers are stable between different assemblies and annotations of the same data without requiring that previous annotations be lifted over by sequence alignment. We assign UniqTag identifiers to nine builds of the Ensembl human genome spanning seven years to demonstrate this stability.
The meta-epigenomic structure of purified human stem cell populations is defined atcis-regulatory sequences
Authors: Wijetunga N. Ari , Delahaye Fabien , Zhao Yong Mei , Golden Aaron , Mar Jessica C. , Einstein Francine H. , Greally John M.
Published: August 2014

The mechanism and significance of epigenetic variability in the same cell type between healthy individuals are not clear. Here, we purify human CD34+ hematopoietic stem and progenitor cells (HSPCs) from different individuals and find that there is increased variability of DNA methylation at loci with properties of promoters and enhancers. The variability is especially enriched at candidate enhancers near genes transitioning between silent and expressed states, and encoding proteins with leukocyte differentiation properties. Our findings of increased variability at loci with intermediate DNA methylation values, at candidate “poised” enhancers, and at genes involved in HSPC lineage commitment suggest that CD34+ cell subtype heterogeneity between individuals is a major mechanism for the variability observed. Epigenomic studies performed on cell populations, even when purified, are testing collections of epigenomes, or meta-epigenomes. Our findings show that meta-epigenomic approaches to data analysis can provide insights into cell subpopulation structure.
A comparison of control samples for ChIP-seq of histone modifications
Authors: Flensburg Christoffer , Kinkel Sarah A , Keniry Andrew , Blewitt Marnie E , Oshlack Alicia
Published: August 2014

The advent of high-throughput sequencing has allowed genome wide profiling of histone modifications by Chromatin ImmunoPrecipitation (ChIP) followed by sequencing (ChIP-seq). In this assay the histone mark of interest is enriched through a chromatin pull-down assay using an antibody for the mark. Due to imperfect antibodies and other factors, many of the sequenced fragments do not originate from the histone mark of interest, and are referred to as background reads. Background reads are not uniformly distributed and therefore control samples are usually used to estimate the background distribution at any given genomic position. The Encyclopedia of DNA Elements (ENCODE) Consortium guidelines suggest sequencing a whole cell extract (WCE, or “input”) sample, or a mock ChIP reaction such as an IgG control, as a background sample. However, for a histone modification ChIP-seq investigation it is also possible to use a Histone H3 (H3) pull-down to map the underlying distribution of histones.

In this paper we generated data from a hematopoietic stem and progenitor cell population isolated from mouse foetal liver to compare WCE and H3 ChIP-seq as control samples. The quality of the control samples is estimated by a comparison to pull-downs of histone modifications and to expression data. We find minor differences between WCE and H3 ChIP-seq, such as coverage in mitochondria and behaviour close to transcription start sites. Where the two controls differ, the H3 pull-down is generally more similar to the ChIP-seq of histone modifications. However, the differences between H3 and WCE have a negligible impact on the quality of a standard analysis.
The Impacts of Historical Barriers on Floristic Patterns of Plant Groups with Different Dispersal Abilities in the Ryukyu Archipelago, Japan
Authors: Nakamura Koh , Suwa Rempei , Denda Tetsuo , Yokota Masatsugu
Published: August 2014

The effects of historical barriers in biogeographical patterns are expected to persist differently depending on dispersal abilities of organisms. We tested two hypotheses that plant groups with different dispersal abilities display different floristic patterns, and that historical barriers can explain floristic differentiation patterns in plants with low dispersal ability but not in plants with higher dispersal ability, in the seed plant flora of the Ryukyu Archipelago. This area is biogeographically interesting because several similar floristic differentiation patterns have been proposed, all of which are primarily explained by two historical barriers, the Tokara Tectonic Strait (Tokara Gap) and the Kerama Gap, which arose during the formation of the islands. We calculated floristic dissimilarity distance among 26 islands based on data sets for three dispersal-ability classes. Clustering analyses based on the floristic dissimilarity distance generated similar floristic patterns regardless of dispersal-ability class. We propose that because the landscape resistance is so strong that migration of plants is severely restricted regardless of their dispersal abilities, the similar floristic differentiation patterns are generated. Multivariate regression analyses using Mantel’s randomization test indicated that floristic differentiations among islands were explained by the both effects of the historical barriers and geographic distance in all dispersal-ability classes. Significance of the historical barriers is not determined by the plant dispersal abilities but presumably by the spatial distribution of the islands, stochastic dispersals, and time since the formation of the barriers.
Calling genotypes from public RNA-sequencing data enables identification of genetic variants that affect gene-expression levels
Authors: Deelen Patrick , Zhernakova Daria , de Haan Mark , van der Sijde Marijke , Bonder Marc Jan , Karjalainen Juha , van der Velde K. Joeri , Abbott Kristin M. , Fu Jingyuan , Wijmenga Cisca , Sinke Richard J. , Swertz Morris A. , Franke Lude
Published: August 2014

Given increasing numbers of RNA-seq samples in the public domain, we studied to what extent expression quantitative trait loci (eQTLs) and allele-specific expression (ASE) can be identified in public RNA-seq data while also deriving the genotypes from the RNA-seq reads. 4,978 human RNA-seq runs, representing many different tissues and cell-types, passed quality control. Even though this data originated from many different laboratories, samples reflecting the same cell-type clustered together, suggesting that technical biases due to different sequencing protocols were limited. We derived genotypes from the RNA-seq reads and imputed non-coding variants. In a joint analysis on 1,262 samples combined, we identified cis-eQTLs effects for 8,034 unique genes. Additionally, we observed strong ASE effects for 34 rare pathogenic variants, corroborating previously observed effects on the corresponding protein levels. Given the exponential growth of the number of publicly available RNA-seq samples, we expect this approach will become relevant for studying tissue-specific effects of rare pathogenic genetic variants.
Faster sequence alignment through GPU-accelerated restriction of the seed-and-extend search space
Authors: Wilton Richard , Budavari Tamas , Langmead Ben , Wheelan Sarah , Salzberg Steven L. , Szalay Alex
Published: August 2014

Motivation

In computing pairwise alignments of biological sequences, software implementations employ a variety of heuristics that decrease the computational effort involved in computing potential alignments. A key element in achieving high processing throughput is to identify and prioritize potential alignments where high-scoring mappings can be expected. These tasks involve listprocessing operations that can be efficiently performed on GPU hardware.

Results

We implemented a read aligner called A21 that exploits GPU-based parallel sort and reduction techniques to restrict the number of locations where potential alignments may be found. When compared with other high-throughput aligners, this approach finds more high-scoring mappings without sacrificing speed or accuracy. A21 running on a single GPU is about 10 times faster than comparable CPU-based tools; it is also faster and more sensitive in comparison with other recent GPU-based aligners.

Availability

The A21 software is open source and available athttps://github.com/RWilton/A21.

Contact

rwilton@pha.jhu.edu

Supplementary information

Supplementary results are available at <<>>
Interactive transcriptome analysis of malaria patients and infectingPlasmodium falciparum
Authors: Yamagishi Junya , Natori Anna , Tolba Mohammed E.M. , Mongan Arthur E. , Sugimoto Chihiro , Katayama Toshiaki , Kawashima Shuichi , Makalowski Wojciech , Maeda Ryuichiro , Eshita Yuki , Tuda Josef , Suzuki Yutaka
Published: August 2014

To understand the molecular mechanisms of parasitism in vivo, it is essential to elucidate how the transcriptomes of the human hosts and the infecting parasites affect one another. Here we report the RNA-seq analysis of 116 Indonesian patients infected with the malaria parasitePlasmodium falciparum(Pf). We extracted RNAs from their peripheral blood as a mixture of host and parasite transcripts and mapped the RNA-seq tags to the human and Pf reference genomes to separate the respective tags. We were thus able to simultaneously analyze expression patterns in both humans and parasites. We identified human and parasite genes and pathways that correlated with various clinical data, which may serve as primary targets for drug developments. Of particular importance, we revealed characteristic expression changes in the human innate immune response pathway genes includingTLR2andTICAM2that correlated with the severity of the malaria infection. We also found a group of transcription regulatory factors,JUND, for example, and signaling molecules,TNFAIP3, for example, that were strongly correlated in the expression patterns of humans and parasites. We also identified several genetic variations in important anti-malaria drug resistance-related genes. Furthermore, we identified the genetic variations which are potentially associated with severe malaria symptoms both in humans and parasites. The newly generated data should collectively lay a unique foundation for understanding variable behaviors of the field malaria parasites, which are far more complex than those observed under laboratory conditions.
Differential retention and divergent resolution of duplicate genes following whole-genome duplication
Authors: McGrath Casey L. , Gout Jean-Francois , Johri Parul , Doak Thomas G. , Lynch Michael
Published: August 2014

TheParamecium aureliacomplex is a group of 15 species that share at least three past whole-genome duplications (WGDs). The macronuclear genome sequences ofP. biaureliaandP. sexaureliaare presented and compared to the published sequence ofP. tetraurelia. Levels of duplicate-gene retention from the recent WGD differ by >10% across species, withP. sexaurelialosing significantly more genes thanP. biaureliaorP. tetraurelia. In addition, historically high rates of gene conversion have homogenized WGD paralogs, probably extending the paralogs’ lifetimes. The probability of duplicate retention is positively correlated with GC content and expression level; ribosomal proteins, transcription factors, and intracellular signaling proteins are overrepresented among maintained duplicates. Finally, multiple sources of evidence indicate thatP. sexaureliadiverged from the two other lineages immediately following, or perhaps concurrent with, the recent WGD, with approximately half of gene losses betweenP. tetraureliaandP. sexaureliarepresenting divergent gene resolutions (i.e., silencing of alternative paralogs), as expected for random duplicate loss between these species. Additionally, thoughP. biaureliaandP. tetraureliadiverged from each other much later, there are still more than 100 cases of divergent resolution between these two species. Taken together, these results indicate that divergent resolution of duplicate genes between lineages acts to reinforce reproductive isolation between species in theParamecium aureliacomplex.
Scanning force microscope forin situnanofocused X-ray diffraction studies
Authors: Ren Zhe , Mastropietro Francesca , Davydok Anton , Langlais Simon , Richard Marie-Ingrid , Furter Jean-Jacques , Thomas Olivier , Dupraz Maxime , Verdier Marc , Beutier Guillaume , Boesecke Peter , Cornelius Thomas W.
Published: August 2014

A compact scanning force microscope has been developed forin situcombination with nanofocused X-ray diffraction techniques at third-generation synchrotron beamlines. Its capabilities are demonstrated on Au nano-islands grown on a sapphire substrate. The newin situdevice allows forin situimaging the sample topography and the crystallinity by recording simultaneously an atomic force microscope (AFM) image and a scanning X-ray diffraction map of the same area. Moreover, a selected Au island can be mechanically deformed using the AFM tip while monitoring the deformation of the atomic lattice by nanofocused X-ray diffraction. Thisin situapproach gives access to the mechanical behavior of nanomaterials.
Winter food limits timing of pre‐alternate moult in a short‐distance migratory bird
Authors: Danner Raymond M. , Greenberg Russell S. , Danner Julie E. , Walters Jeffrey R.
Published: August 2014

Moult is critical for fitness for many organisms for several reasons: it allows growth and maintains the function of the integument for protection, thermoregulation and communication.

Feather moult in birds is costly and therefore typically does not overlap with migration or reproduction. In spring, the rapid succession of pre‐alternate moult, migration (if a migrant) and breeding suggests that timing of moult could constrain the initiation of breeding. A trade‐off between time spent moulting and breeding might also limit moult quality.

The proximate basis for the timing of pre‐alternate moult initiation is not well known, although it typically occurs during a resource poor time of year. Food limitation combined with fitness consequences of moulting earlier suggests that plasticity in timing of pre‐alternate moult in response to food abundance should be advantageous.

We experimentally tested, for the first time, if food abundance influences the timing of moult in the wild. We conducted a controlled food supplementation experiment on free‐living swamp sparrows (Melospiza georgiana) preceding and during the time of natural pre‐alternate moult (January–March 2009, 2010).

Supplemented birds began moulting the body, face and crown earlier than control birds (11, 14, and 8 days earlier, respectively), indicating that food abundance limits the initiation of moult. Along with interannual variation, these results indicate that photoperiod is not the sole cue for initiation of moult.

Both control and supplemented birds moulted in sequence, starting with the body, followed by the crown 9 days later, and the face 11 days after the body. The presence of a sequence further suggests energetic limitation of moult or possibly a strategy to moult‐specific regions first to ensure completion or growth at an optimal time.

This study provides novel experimental evidence that food abundance can: (i) limit pre‐alternate moult timing and (ii) limit moult timing in the wild. Food limitation of moult timing could allow earlier breeding or production of higher quality feathers and thus cascade through other life‐history stages and affect reproductive success. These results indicate that food availability is a cue for moult initiation, possibly acting secondarily to photostimulation.
Higher establishment success in specialized parasitoids: support for the existence of trade‐offs in the evolution of specialization
Authors: Rossinelli Silvia , Bacher Sven
Published: August 2014

Most animals do not feed on all the resources available to them, but the mechanisms behind the evolution of dietary specialization are still debated. A central but unanswered question is whether specialists generally gain fitness advantages on their resource compared to generalists, experiencing a trade‐off between the ability to use a broad range of resources and the fitness reached on each single one.

Empirical tests so far suffered from difficulties in measuring fitness; they were restricted to few species, and results were equivocal. This lack of support for the importance of trade‐offs gave rise to theories explaining the evolution of specialization without such trade‐offs.

Using a large dataset of intentional biological control introductions of 254 species of parasitoids from 15 families to locations outside their native range, we show that establishment success, a measure of total fitness, is higher in specialized species. This result holds when controlling for possible confounding factors such as the number of introduced individuals (propagule pressure).

The outcome of this study provides robust evidence that dietary specialization implies fitness advantages in an entire species‐rich taxon, indicating that trade‐offs might be widely involved in the evolution of specialization.
“Urban Ecology Under Fire”: Water Supply in Madrid During the Spanish Civil War (1936–1939)
Authors: Gorostiza Santiago , March Hug , Sauri David
Published: August 2014

This paper investigates the critical role of workers to enhance the resilience of water supply services in cities at war through analyzing the case of Madrid and the Madrid water company Canales del Lozoya during the Spanish Civil War (1936–1939). We argue that securing the protection of vital urban flows mediated through infrastructures is a key objective of cities under attack. In doing so we contend that examining how those affected by the interruption of these flows cope with the situation represents a valuable but largely neglected form of water management. We illustrate how quotidian knowledge about the urban geography of water flows may have important repercussions for the war effort itself. In a nutshell, the case of Madrid offers an early account of the critical role of water workers in sustaining “urban ecologies under fire” securing the complex urban metabolism while also contributing to the struggle against invading forces.
Detrital thermochronologic record of burial heating and sediment recycling in the Magallanes foreland basin, Patagonian Andes
Authors: Fosdick Julie C. , Grove Marty , Graham Stephan A. , Hourigan Jeremy K. , Lovera Oscar , Romans Brian W.
Published: August 2014

The Patagonian Magallanes retroarc foreland basin affords an excellent case study of sediment burial recycling within a thrust belt setting. We report combined detrital zircon U–Pb geochronology and (U–Th)/He thermochronology data and thermal modelling results that confirm delivery of both rapidly cooled, first‐cycle volcanogenic sediments from the Patagonian magmatic arc and recycled sediment from deeply buried and exhumed Cretaceous foredeep strata to the Cenozoic depocentre of the Patagonian Magallanes basin. We have quantified the magnitude of Eocene heating with thermal models that simultaneously forward model detrital zircon (U–Th)/He dates for best‐fit thermal histories. Our results indicate that 54–45 Ma burial of the Maastrichtian Dorotea Formation produced 164–180 °C conditions and heating to within the zircon He partial retention zone. Such deep burial is unusual for Andean foreland basins and may have resulted from combined effects of high basal heat flow and high sediment accumulation within a rapidly subsiding foredeep that was floored by basement weakened by previous Late Jurassic rifting. In this interpretation, Cenozoic thrust‐related deformation deeply eroded the Dorotea Formation fromca. 5 km burial depths and may be responsible for the development of a basin‐wide Palaeogene unconformity. Results from the Cenozoic Río Turbio and Santa Cruz formations confirm that they contain both Cenozoic first‐cycle zircon from the Patagonian magmatic arc and highly outgassed zircon recycled from older basin strata that experienced burial histories similar to those of the Dorotea Formation.