bluuebunny/crossref_metadata_2025 huggingface dataset:
Biased interpretations of ambiguous bodily threat information in adolescents with chronic pain
Authors: Heathcote L.C. , Jacobs K. , Eccleston C. , Fox E. , Lau J.Y.F.
Published: January 2017

Adult patients with chronic pain are consistently shown to interpret ambiguous health and bodily information in a pain-related and threatening way. This interpretation bias may play a role in the development and maintenance of pain and disability. However, no studies have yet investigated the role of interpretation bias in adolescent patients with pain, despite that pain often first becomes chronic in youth. We administered the Adolescent Interpretations of Bodily Threat (AIBT) task to adolescents with chronic pain (N = 66) and adolescents without chronic pain (N = 74). Adolescents were 10 to 18 years old and completed the study procedures either at the clinic (patient group) or at school (control group). We found that adolescents with chronic pain were less likely to endorse benign interpretations of ambiguous pain and bodily threat information than adolescents without chronic pain, particularly when reporting on the strength of belief in those interpretations being true. These differences between patients and controls were not evident for ambiguous social situations, and they could not be explained by differences in anxious or depressive symptoms. Furthermore, this interpretation pattern was associated with increased levels of disability among adolescent patients, even after controlling for severity of chronic pain and pain catastrophizing. The current findings extend our understanding of the role and nature of cognition in adolescent pain, and provide justification for using the AIBT task in longitudinal and training studies to further investigate causal associations between interpretation bias and chronic pain.
What are the most promising new agents in acute myeloid leukemia?
Authors: Sallman David A. , Lancet Jeffrey E.
Published: January 2017

Purpose of review

Although the treatment paradigm for acute myeloid leukemia (AML) had been largely unchanged for many years, in-depth molecular characterization has revolutionized our understanding of mutations that drive the disease, subsequently serving to guide current clinical investigation. Furthermore, recent advances in the field have highlighted the importance of optimizing known efficacious agents by improving drug delivery or bypassing resistance mechanisms. The current status of novel agents which are shaping the clinical management of AML patients are summarized in this review.

Recent findings

Practice changing findings over the past year include improved overall survival (OS) in a molecularly defined AML subgroup as well as in elderly patients with secondary AML (sAML). Specifically, synergistic combination of daunorubicin and cytarabine (i.e., CPX-351) was found to improve OS in sAML patients. Furthermore, although multiple mutation specific inhibitors have been developed, optimal combination with additional agents appears critical, as monotherapies have not resulted in durable remissions or improved outcomes. Improved OS via the addition of midostaurin to intensive chemotherapy in FLT3 mutant AML supports this concept.

For the first time in AML, personalized therapy has become possible through improved understanding of the molecular architecture and survival pathways of an individual's disease. The landscape of AML treatment is encouraging, with multiple novel agents likely to gain approval over the next 5 years.
‘JAK–ing’ up the treatment of primary myelofibrosis: building better combination strategies
Authors: Assi Rita , Verstovsek Srdan , Daver Naval
Published: January 2017

Purpose of review

The article discusses the promising agents that are approved or currently under investigation for the treatment of myelofibrosis and reviews the ongoing Janus kinase (JAK) inhibitors–based combinatorial strategies in this setting.

Recent findings

Myelofibrosis is a Philadelphia-negative myeloproliferative neoplasm with constitutive JAK/STAT activation. The JAK-inhibitor ruxolitinib is the only approved drug for this disease in the United States and Europe based on two randomized phase III studies that demonstrated clinically meaningful reduction in spleen size, improvement in symptoms, quality of life, and an overall survival advantage with prolonged follow-up. Emerging data have revealed the complex molecular architecture of myelofibrosis with clonal evolution playing a central role in disease progression or transformation. These molecular pathways may explain the heterogeneous benefits obtained by JAK-inhibitors in patients with myelofibrosis. In addition, the genetic and epigenetic mutations appear to work in concert with overactive JAK/STAT signaling and contribute to myelofibrosis pathogenesis and prognosis, suggesting a potential to exploit them as potential therapeutic targets.

Combining JAK-inhibitors with agents that target parallel prosurvival pathways or agents that enhance hematopoiesis may enhance efficacy and/or mitigate on-target myelosuppression, thereby extending the therapeutic benefits observed with JAK-inhibitors alone.
A Fatal Case of Coin Battery Ingestion in an 18-Month-Old Child
Authors: Ventura Francesco , Candosin Sara , Barranco Rosario , Bonsignore Alessandro , Andrello Luisa , Tajana Luca , Osculati Antonio
Published: January 2017

The ingestion of extraneous substances is quite common in clinical practice; it usually befalls in the pediatric age, mostly between 6 months and 6 years. In most cases, complications do not emerge, and the prognosis is considered favorable. However, when a case of battery ingestion occurs, serious adverse events may develop. The ingestion of these components is a potential life-threatening event for children.

In this article, we report the case of an 18-month-old child who died from hemorrhagic shock due to an aortoesophageal fistula caused by a 20 mm lithium button battery lodged in the esophagus.

The child presented vomiting blood, and laboratory results revealed a severe anemization, which later led to death.

The autopsy showed a coin battery located in the middle third of the esophagus as well as a transmural erosion of the esophageal wall with fistulization into the aortic wall. The histological examination revealed a severe necrosis of the esophageal and aortic walls in line with the junction between the aortic arch and the descending part.
Perioperative Near-Infrared Spectroscopy Monitoring in Neonates With Congenital Heart Disease: Relationship of Cerebral Tissue Oxygenation Index Variability With Neurodevelopmental Outcome
Authors: Spaeder Michael C. , Klugman Darren , Skurow-Todd Kami , Glass Penny , Jonas Richard A. , Donofrio Mary T.
Published: January 2017

Objectives:

To evaluate the value of perioperative cerebral near-infrared spectroscopy monitoring using variability analysis in the prediction of neurodevelopmental outcomes in neonates undergoing surgery for congenital heart disease.

Design:

Retrospective cohort study.

Setting:

Urban, academic, tertiary-care children’s hospital.

Patients:

Neonates undergoing surgery with cardiopulmonary bypass for congenital heart disease.

Interventions:

Perioperative monitoring of continuous cerebral tissue oxygenation index by near-infrared spectroscopy and subsequent neurodevelopmental testing at 6, 15, and 21 months of age.

Measurements and Main Results:

We developed a new measure, cerebral tissue oxygenation index variability, using the root mean of successive squared differences of averaged 1-minute cerebral tissue oxygenation index values for both the intraoperative and first 24-hours postoperative phases of monitoring. There were 62 neonates who underwent cerebral tissue oxygenation index monitoring during surgery for congenital heart disease and 44 underwent subsequent neurodevelopmental testing (12 did not survive until testing and six were lost to follow-up). Among the 44 monitored patients who underwent neurodevelopmental testing, 20 (45%) had abnormal neurodevelopmental indices. Patients with abnormal neurodevelopmental indices had lower postoperative cerebral tissue oxygenation index variability when compared with patients with normal indices (p= 0.01). Adjusting for class of congenital heart disease and duration of deep hypothermic circulatory arrest, lower postoperative cerebral tissue oxygenation index variability was associated with poor neurodevelopmental outcome (p= 0.02).

Conclusions:

We found reduced postoperative cerebral tissue oxygenation index variability in neonatal survivors of congenital heart disease surgery with poor neurodevelopmental outcomes. We hypothesize that reduced cerebral tissue oxygenation index variability may be a surrogate for impaired cerebral metabolic autoregulation in the immediate postoperative period. Further research is needed to investigate clinical implications of this finding and opportunities for using this measure to drive therapeutic interventions.
Pain Assessment in Children Younger Than 8 Years in Out-of-Hospital Emergency Medicine
Authors: Beltramini Alexandra , Galinski Michel , Chabernaud Jean Louis , Ruiz Almenar Ramon , Tsapis Michael , Goddet Nathalie Sybille , Kessous Katia , Falissard Bruno , Fournier-Charrière Elisabeth
Published: January 2017

Objective

Pain in children is underestimated and undertreated in out-of-hospital emergency medicine. In this setting, caregivers need a reliable pain scale, but none has been validated. A single observational pain scale for all children younger than 8 years, EVENDOL, has been validated in emergency pediatric units. We study the feasibility of EVENDOL score in an out-of-hospital emergency setting.

Methods

This prospective multicenter study included all conscious children younger than 8 years transported by a mobile intensive care unit between October 2008 and May 2010. The emergency physician and nurse independently assessed the child’s pain using first a numeric rating scale (score 0-10), then the 5-item EVENDOL scale (verbal/vocal expression, facial expression, movements, postures, and relationship with entourage) (score 0-3/item) at 3 time points (at rest, during examination, and after analgesia). We studied the scale’s internal validity, interrater reliability, discriminant ability (influence of fever and anxiety), and face validity.

Results

Of the 422 included children, 82 and 62 (29%–39%) were in pain according to the emergency physician and nurses (numeric rating scale >3/10). All EVENDOL scale attributes were satisfied at all 3 time points, for all population subsets. Values for the first assessment (entire study population) were as follows: internal validity (0.78–0.89), interrater reliability (r = 0.63–0.76, weighted κ = 0.49–0.65), construct validity, and discriminant ability (r = 0.6–0.7). Fever did not impact on EVENDOL score. Anxiety level and pain were correlated. Completion time was fast (mean, 2.3–3.4 minutes). Face validity was good.

Conclusion

EVENDOL is a quick, easy-to-use, discriminant instrument to assess pain in young children in out-of-hospital emergency settings.
Parent Perceptions on Transfers to Pediatric Emergency Departments and the Role of Telemedicine
Authors: Mollen Cynthia J. , Henien Mira , Jacobs Lisa M. , Myers Sage
Published: January 2017

Objective

Real-time audiovisual consultation (telemedicine) has been proven feasible and is a promising alternative to interfacility transfer. We sought to describe caregiver perceptions of the decision to transfer his or her child to a pediatric emergency department and the potential use of telemedicine as an alternative to transfer.

Methods

Semistructured interviews of caregivers of patients transferred to a pediatric emergency department. Purposive sampling was used to recruit caregivers of patients who were transferred from varying distances and different times of the day. Interviews were conducted in person or on the phone by a trained interviewer. Interviews were recorded, transcribed, and analyzed using modified grounded theory.

Results

Twenty-three caregivers were interviewed. Sixteen (70%) were mothers; 57% of patients were transported from hospitals outside of the city limits. Most caregivers reported transfer for a specific resource need, such as a pediatric subspecialist. Generally, caregivers felt that the decision to transfer was made unilaterally by the treating physician, although most reported feeling comfortable with the decision. Almost no one had heard about telemedicine; after hearing a brief description, most were receptive to the idea. Caregivers surmised that telemedicine could reduce the risks and cost associated with transfer. However, many felt telemedicine would not be applicable to their particular situation.

Conclusions

In this sample, caregivers were comfortable with the decision to transfer their child and identified potential benefits of telemedicine as either an adjunct to or replacement of transfer. As hospitals use advanced technology, providers should consider families' opinions about risks and out-of-pocket costs and tailoring explanations to address individual situations.
The microbiome in mechanically ventilated patients
Authors: Yin Yudong , Hountras Peter , Wunderink Richard G.
Published: January 2017

Purpose of review

Discovery of a normal lung microbiome requires reassessment of our concepts of HAP/VAP pathogenesis and has important implications for clinical diagnosis and management.

Recent findings

Changes in the microbiome of dental plaque are associated with increased risk of HAP/VAP. A transition to a lung microbiome enriched with gut flora is found in ARDS with an increased inflammatory response in patients with this change in microbial flora. A characteristic microbiome pattern of higher amounts of bacterial DNA, lower community diversity, and greater relative abundance of a single species characterize pneumonia and occasionally identify bacteria not found in culture. The influence of the microbiome makes probiotics a logical strategy to prevent or ameliorate HAP/VAP but so far clinical support is unclear.

The presence of a normal lung microbiome and the interaction of that microbiome with other microbiota have an important but previously overlooked impact on the pathogenesis of HAP/VAP. Deep sequencing suggests that the repertoire of microorganisms and the pattern of bacterial communities associated with HAP/VAP remains incompletely understood but recent studies are adding greater clarity.
Resident Education in Female Pelvic Medicine and Reconstructive Surgery
Authors: Propst Katie , Steinberg Adam C. , O’Sullivan David M. , Schimpf Megan O. , LaSala Christine
Published: January 2017

Objective

The aim of this study was to evaluate whether obstetrics and gynecology trainees feel satisfied with the female pelvic medicine and reconstructive surgery (FPMRS) education received in residency.

Methods

This is a survey study of obstetrics and gynecology residents in the United States and Puerto Rico during the 2015–2016 academic year. The anonymous 29-question survey was approved by the Hartford HealthCare institutional review board. Responses were included only if the trainee had ever rotated on the FPMRS service. Descriptive analyses were performed using mean and SD for continuous data; categorical data were described using frequencies, expressed as percentages. The results were analyzed for statistical significance using χ2 for categorical variables and Student t test for continuous variables. All results yielding P < 0.05 were deemed statistically significant.

Results

Of the 333 responses received, 172 met criteria for inclusion. Regarding amount of training in FPMRS, 126 trainees (73.3%) reported satisfaction, 40 (23.3%) reported too little training, and 6 trainees (3.5%) reported too much. Residents in programs with a board-certified FPMRS surgeon more commonly reported satisfaction with training (75.0 vs 28.6%, P = 0.02). When fourth-year residents were asked if they would feel comfortable performing specific surgical procedures independently after graduation, the percentage answering affirmatively ranged from 23.6% to 98.8%.

Conclusions

Satisfaction with training in FPMRS has improved, but poor confidence performing surgical procedures compared with previous reports demonstrates that improvements in resident training are still needed.
Increasing Age Is a Risk Factor for Decreased Postpartum Pelvic Floor Strength
Authors: Quiroz Lieschen H. , Pickett Stephanie D. , Peck Jennifer D. , Rostaminia Ghazaleh , Stone Daniel E. , Shobeiri S. Abbas
Published: January 2017

Objectives

This study aimed to determine factors associated with decreased pelvic floor strength (PFS) after the first vaginal delivery (VD) in a cohort of low-risk women.

Methods

This is a secondary analysis of a prospective study examining the risk of pelvic floor injury in a cohort of primiparous women. All recruited participants underwent an examination, three-dimensional ultrasound and measurement of PFS in the third trimester and repeated at 4 weeks to 6 months postpartum using a perineometer.

Results

There were 84 women recruited for the study, and 70 completed the postpartum assessment. Average age was 28.4 years (standard deviation, 4.8). There were 46 (66%) subjects with a VD and 24 (34%) with a cesarean delivery who labored. Decreased PFS was observed more frequently in the VD group compared with the cesarean delivery group (68% vs 42%, P = 0.03).

In modified Poisson regression models controlling for mode of delivery and time of postpartum assessment, women who were aged 25 to 29 years (risk ratio = 2.80, 95% confidence interval, 1.03–7.57) and 30 years and older (risk ratio = 2.53, 95% confidence interval, 0.93–6.86) were over 2.5 times more likely to have decreased postpartum PFS compared with women younger than 25 years.

Conclusions

In this population, women aged 25 years and older were more than twice as likely to have a decrease in postpartum PFS.
Association Between Obesity and Perioperative Morbidity in Open Versus Laparoscopic Sacrocolpopexy
Authors: Halder Gabriela E. , Salemi Jason L. , Hart Stuart , Mikhail Emad
Published: January 2017

Objectives

The aim of this study was to compare differences in 30-day perioperative morbidity and mortality for women undergoing open sacrocolpopexy (OSCP) versus laparoscopic sacrocolpopexy (LSCP) across all body mass index (BMI) groups and between patients of ideal versus elevated BMI (includes overweight, obese, and morbidly obese).

Materials and Methods

Data for this retrospective review were obtained from the American College of Surgeons-National Surgical Quality Improvement Project database using current procedural terminology. All women older than 18 years who underwent an OSCP or LSCP from 2005 to 2013 were included. Patients were divided into 4 BMI (weight [kg]/[height (m)]2) subgroups: (1) less than 25, (2) 25 to 29.9, (3) 30 to 39.9, and (4) 40 or greater. The data were analyzed using Student t or χ2 test and Fisher exact test.

Results

A total of 4894 women underwent an OSCP or LSCP. Shorter operative times were observed with OSCP (P < 0.05) in all BMI groups except morbidly obese patients. Compared with patients of ideal body weight, overweight and obese patients had significantly longer operation times during LSCP (P < 0.05), a difference that was not observed during OSCP. For all BMI subgroups, the length of hospital stay was significantly shorter for LSCP (1 [1–1]) versus OSCP (2 [2–3]) (P < 0.05). Statistically significant increases in the rate of superficial surgical site infections were observed in OSCP in patients of both ideal and overweight BMIs (P < 0.05).

Conclusions

Obesity increases the operative time during LSCP. For patients in all BMI groups, LSCP offers the benefit of shorter hospital stays when compared with OSCP.
Construction and optimization of a heterologous pathway for protocatechuate catabolism inEscherichia colienables rapid bioconversion of model lignin monomers
Authors: Clarkson Sonya M. , Kridelbaugh Donna M. , Elkins James G. , Guss Adam M. , Michener Joshua K.
Published: January 2017

Cellulosic biofuel production yields a substantial lignin byproduct stream that currently has few applications. Biological conversion of lignin compounds into chemicals and fuels has the potential to improve the economics of cellulosic biofuels, but few microbes are able both to catabolize lignin and generate valuable products. WhileEscherichia colihas been engineered to produce a variety of fuels and chemicals, it is incapable of catabolizing most aromatic compounds. Therefore, we have engineeredE. colito catabolize a model lignin monomer, protocatechuate, as the sole source of carbon and energy, via heterologous expression of a nine-gene pathway fromPseudomonas putidaKT2440. We next used experimental evolution to select for mutations that increased growth with PCA more than two-fold. Increasing the strength of a single ribosome binding site in the heterologous pathway was sufficient to recapitulate the increased growth. After optimization of the core pathway, we extended the pathway to enable catabolism of a second model compound, 4-hydroxybenzoate. These engineered strains will be useful platforms to discover, characterize, and optimize pathways for lignin bioconversions.

Highlights

A heterologous pathway for PCA catabolism was transferred to Escherichia coli.

Evolution identified a mutation that increased growth with PCA by 2.5-fold.

Optimization plus further engineering allowed efficient catabolism of 4-HB
The Early Pregnancy Human Placenta Shares Hypomethylation Patterns Characteristic of Solid Tumors
Authors: Nordor Akpéli V. , Nehar-Belaid Djamel , Richon Sophie , Klatzmann David , Bellet Dominique , Dangles-Marie Virginie , Fournier Thierry , Aryee Martin J.
Published: January 2017

Background

The placenta relies on phenotypes that are characteristic of cancer to successfully implant the embryo in the uterus during early pregnancy. Notably, it has to invade its host tissues, promote angiogenesis, while surviving hypoxia, and escape the immune system. Similarities in DNA methylation patterns between the placenta and cancers suggest that common epigenetic mechanisms may be involved in regulating these behaviors.

Results

We show here that megabase-scale patterns of hypomethylation distinguish first from third trimester chorionic villi in the placenta, and that these patterns mirror those that distinguish many tumors from corresponding normal tissues. We confirmed these findings in villous cytotrophoblasts isolated from the placenta and identified a time window at the end of the first trimester, when these cells come into contact with maternal blood as the likely time period for the methylome alterations. Furthermore, the large genomic regions affected by these patterns of hypomethylation encompass genes involved in pathways related to epithelial-mesenchymal transition (EMT), immune response and inflammation. Analyses of expression profiles corresponding to genes in these hypomethylated regions in colon adenocarcinoma tumors point to networks of differentially expressed genes previously implicated in carcinogenesis and placentogenesis, where nuclear factor kappa B (NF-kB) is a key hub.

Conclusion

Taken together, our results suggest the existence of epigenetic switches involving large-scale changes of methylation in the placenta during pregnancy and in tumors during neoplastic transformation. The characterization of such epigenetic switches might lead to the identification of biomarkers and drug targets in oncology as well as in obstetrics and gynecology.
Local differentiation in the defensive morphology of an invasive zooplankton species is not genetically based
Authors: Fiorino Giuseppe E. , McAdam Andrew G.
Published: January 2017

Evolutionary changes in functional traits represent one possible reason why exotic species spread to become invasive, but empirical studies of the mechanisms driving phenotypic differentiation between populations of invasive species are rare. This study tested whether differences in distal spine length among populations of the invasive cladoceran,Bythotrephes longimanus, could be explained by local adaptation or phenotypic plasticity. We collectedBythotrephesfrom six lakes and found that distal spine lengths and natural selection on distal spine length differed among populations, but were unrelated to the gape-limitation of the dominant fish predator in the lake from which they were collected. A common garden experiment revealed significant genetic and maternal variation for distal spine length, but phenotypic differences among populations were not genetically based. Phenotypic differences among lakes in this ecologically important trait are, therefore, the result of plasticity and not local adaptation, despite spatially variable selection on this heritable trait. The ability ofBythotrephesto plastically adjust distal spine length may explain the success of this species at invading lake ecosystems with diverse biotic environments.
Reverse Watson-Crick purine-purine base pairs — the Sharp-turn motif and other structural consequences in functional RNAs
Authors: Mittal Abhinav , Halder Antarip , Bhattacharya Sohini , Bhattacharyya Dhananjay , Mitra Abhijit
Published: January 2017

Identification of static and/or dynamic roles of different noncanonical base pairs is essential for a comprehensive understanding of the sequence-structure-function space of RNA. In this context, reverse Watson-Crick purine-purine base pairs (A:A, G:G&A:GW:W Trans) constitute an interesting class of noncanonical base pairs in RNA due to their characteristic C1′–C1′ distance (highest among all base pairing geometries) and parallel local strand orientation. Structural alignment of the RNA stretches containing these W:W Trans base pairs with their corresponding homologous sites in a non-redundant set of RNA crystal structures show that, as expected, these base pairs are associated with specific structural folds or functional roles. Detailed analysis of these contexts further revealed a bimodal distribution in the local backbone geometry parameters associated with these base pairs. One mode, populated by both A:A and G:G W:W Trans pairs, manifests itself as a characteristic backbone fold. We call this fold a ‘Sharp-turn’ motif. The other mode is exclusively associated with A:A W:W Trans pairs involved in mediating higher order interactions. The same trend is also observed in available solution NMR structures. We have also characterized the importance of recurrent hydrogen bonding interactions between adenine and guanine in W:W Trans geometry. Quantum chemical calculations performed at M05-2X/6-31++(2d,2p) level explain how the characteristic electronic properties of these W:W Trans base pairs facilitate their occurrence in such exclusive structural folds that are important for RNA functionalities.
MinorityReport, software for generalized analysis of causal genetic variants
Authors: Horst Jeremy A , Wu Wesley , DeRisi Joseph L
Published: January 2017

Background

The widespread availability of next generation genome sequencing technologies has enabled a wide range of variant detection applications, especially in cancer and inborn genetic disorders. For model systems and microorganisms, the same technology may be used to discover the causative mutations for any phenotype, including those generated in response to chemical perturbation. In the case of pathogenic organisms, these approaches have allowed the determination of drug targets by means of resistance selection followed by genome sequencing.

Results

Here, we present open source software written in python, MinorityReport, to facilitate the comparison of any two sets of genome alignments for the purpose of rapidly identifying the spectrum of nonsynonymous changes, insertions or deletions, and copy number variations in a presumed mutant relative to its parent. Specifically, MinorityReport relates mapped sequence reads in SAM format output from any alignment tool for both the mutant and parent genome, relative to a reference genome, and produces the set of variants that distinguishes the mutant from the parent, all presented in an intuitive, straightforward report format. MinorityReport features tunable parameters for evaluating evidence and a scoring system that prioritizes reported variants based on relative proportions of read counts supporting the variant in the mutant versus parent data sets. We demonstrate the utility of MinorityReport using publicly available data sets that we previously published to find the determinants of resistance for novel anti-malarial drugs.

Conclusions

MinorityReport is readily available (github: xxxxxxx) to identify the genetic mechanisms of drug resistance in plasmodium, genotype-phenotype relationships in human diads, or genomic variations between any two related organisms.
Cyclic-di-GMP is required for corneal infection byPseudomonas aeruginosaand modulates host immunity
Authors: Yam Joey Kuok Hoong , Aung Thet Tun , Chua Song Lin , Cheng Yingying , Kohli Gurjeet Singh , Zhou Jianuan , Constancias Florentin , Liu Yang , Cai Zhao , Salido May Margarette Santillan , Drautz-Moses Daniela I. , Rice Scott A. , Schuster Stephan Christoph , Wu Bin , Kjelleberg Staffan , Tolker-Nielsen Tim , Beuerman Roger W. , Givskov Michael , Yang Liang
Published: January 2017

Biofilms are extremely tolerant toward antimicrobial treatment and host immune clearance due to their distinct physiology and protection by extracellular polymeric substances. Bis-(3´-5´)-cyclic dimeric guanosine monophosphate (c-di-GMP) is an essential messenger that regulates biofilm formation by a wide range of bacteria. However, there is a lack of physiological characterization of biofilmsin vivoas well as the roles of c-di-GMP signaling in mediating host-biofilm interactions. Here, we employed dual RNA-Seq to characterize the host and pathogen transcriptomes duringPseudomonas aeruginosainfection using a mouse keratitis model.In vivo P. aeruginosabiofilms maintained a distinct physiology compared within vitro P. aeruginosabiofilms, with enhanced virulence and iron uptake capacity. C-di-GMP synthesis was enhanced inP. aeruginosacellsin vivo,potentially due to down-regulation of the expression of several phosphodiesterases (e.g., DipA, NbdA). Increased intracellular c-di-GMP levels were required for long-term ocular colonization ofP. aeruginosaand impaired host innate immunity.
Deciphering HLA-I motifs across HLA peptidomes improves neo-antigen predictions and identifies allostery regulating HLA specificity
Authors: Bassani-Sternberg Michal , Chong Chloé , Guillaume Philippe , Solleder Marthe , Pak HuiSong , Gannon Philippe O , Kandalaft Lana E , Coukos George , Gfeller David
Published: January 2017

The precise identification of Human Leukocyte Antigen class I (HLA-I) binding motifs plays a central role in our ability to understand and predict (neo-)antigen presentation in infectious diseases and cancer. Here, by exploiting co-occurrence of HLA-I alleles across ten newly generated as well as forty public HLA peptidomics datasets comprising more than 115,000 unique peptides, we show that we can rapidly and accurately identify many HLA-I binding motifs and map them to their corresponding alleles without anya prioriknowledge of HLA-I binding specificity. Our approach recapitulates and refines known motifs for 43 of the most frequent alleles, uncovers new motifs for 9 alleles that up to now had less than five known ligands and provides a scalable framework to incorporate additional HLA peptidomics studies in the future. The refined motifs improve neo-antigen and cancer testis antigen predictions, indicating that unbiased HLA peptidomics data are ideal forin silicopredictions of neo-antigens from tumor exome sequencing data. The new motifs further reveal allosteric modulation of the binding specificity of HLA-I alleles and we unravel the underlying mechanisms by protein structure analysis, mutagenesis andin vitrobinding assays.
Integration of visual information in auditory cortex promotes auditory scene analysis through multisensory binding
Authors: Atilgan Huriye , Town Stephen M. , Wood Katherine C. , Jones Gareth P. , Maddox Ross K. , Lee Adrian K.C. , Bizley Jennifer K.
Published: January 2017

How and where in the brain audio-visual signals are bound to create multimodal objects remains unknown. One hypothesis is that temporal coherence between dynamic multisensory signals provides a mechanism for binding stimulus features across sensory modalities. Here we report that when the luminance of a visual stimulus is temporally coherent with the amplitude fluctuations of one sound in a mixture, the representation of that sound is enhanced in auditory cortex. Critically, this enhancement extends to include both binding and non-binding features of the sound. We demonstrate that visual information conveyed from visual cortex, via the phase of the local field potential is combined with auditory information within auditory cortex. These data provide evidence that early cross-sensory binding provides a bottom-up mechanism for the formation of cross-sensory objects and that one role for multisensory binding in auditory cortex is to support auditory scene analysis.
Time-resolved dual root-microbe transcriptomics reveals early induced Nicotiana benthamiana genes and conserved infection-promoting Phytophthora palmivora effectors
Authors: Evangelisti Edouard , Gogleva Anna , Hainaux Thomas , Doumane Mehdi , Tulin Frej , Quan Clément , Yunusov Temur , Floch Kevin , Schornack Sebastian
Published: January 2017

Background

Plant-pathogenic oomycetes are responsible for economically important losses on crops worldwide. Phytophthora palmivora, a broad-host-range tropical relative of the potato late blight pathogen, causes rotting diseases in many important tropical crops including papaya, cocoa, oil palm, black pepper, rubber, coconut, durian, mango, cassava and citrus.

Transcriptomics have helped to identify repertoires of host-translocated microbial effector proteins which counteract defenses and reprogram the host in support of infection. As such, these studies have helped understanding of how pathogens cause diseases. Despite the importance of P. palmivora diseases, genetic resources to allow for disease resistance breeding and identification of microbial effectors are scarce.

Results

We employed the model plant N. benthamiana to study the P. palmivora root infections at the cellular and molecular level. Time-resolved dual transcriptomics revealed different pathogen and host transcriptome dynamics. De novo assembly of P. palmivora transcriptome and semi-automated prediction and annotation of the secretome enabled robust identification of conserved infection-promoting effectors. We show that one of them, REX3, suppresses plant secretion processes. In a survey for early transcriptionally activated plant genes we identified a N. benthamiana gene specifically induced at infected root tips that encodes a peptide with danger-associated molecular features.

Conclusions

These results constitute a major advance in our understanding of P. palmivora diseases and establish extensive resources for P. palmivora pathogenomics, effector-aided resistance breeding and the generation of induced resistance to Phytophthora root infections. Furthermore, our approach to find infection relevant secreted genes is transferable to other pathogen-host interactions and not restricted to plants.
Evolution of the Mineralocorticoid Receptor: Sequence, Structure and Function
Authors: Baker Michael E. , Katsu Yoshinao
Published: January 2017

The mineralocorticoid receptor (MR) is descended from a corticoid receptor (CR), which has descendants in lamprey and hagfish, cyclostomes (jawless fish), a taxon that evolved at the base of the vertebrate line. A distinct MR and GR first appear in cartilaginous fishes (Chondrichthyes), such as sharks, skates, rays and chimaeras. Skate MR has a strong response to corticosteroids that are mineralocorticoids and glucocorticoids in humans. The half-maximal responses (EC50s) for skate MR for the mineralocorticoids aldosterone and 11-deoxycorticosterone are 0.07 nM and 0.03 nM, respectively. EC50s for the glucocorticoids cortisol and corticosterone are 1 nM and 0.09 nM, respectively. The physiological mineralocorticoid in ray-finned fish, which do not synthesize aldosterone, is not fully understood because several 3-ketosteroids, including cortisol, 11-deoxycortisol, corticosterone, 11-deoxycorticosterone and progesterone are transcriptional activators of fish MR. Divergence of the MR and GR in terrestrial vertebrates, which synthesize aldosterone, led to increased selectivity of the MR for aldosterone, coupled with a diminished response to cortisol and corticosterone. Here, we combine sequence analysis of the CR and vertebrate MRs and GRs, analysis of crystal structures of human MR and GR and data on transcriptional activation by 3-ketosteroids of wild-type and mutant MRs and GRs to investigate the evolution of selectivity for 3-ketosteroids by the MR in terrestrial vertebrates and ray-finned fish, as well as the basis for binding of some glucocorticoids by human MR and other vertebrate MRs.
Chunking as a rational strategy for lossy data compression in visual working memory
Authors: Nassar Matthew R. , Helmers Julie C. , Frank Michael J.
Published: January 2017

The nature of capacity limits for visual working memory has been the subject of an intense debate that has relied on models that assume items are encoded independently. Here we propose that instead, similar features are jointly encoded through a “chunking” process to optimize performance on visual working memory tasks. We show that such chunking can: 1) facilitate performance improvements for abstract capacity-limited systems, 2) be optimized through reinforcement, 3) be implemented by center-surround dynamics, and 4) increase effective storage capacity at the expense of recall precision. Human performance on a variant of a canonical working memory task demonstrated performance advantages, precision detriments, inter-item dependencies, and trial-to-trial behavioral adjustments diagnostic of performance optimization through center-surround chunking. Models incorporating center-surround chunking provided a better quantitative description of human performance in our study as well as in a meta-analytic dataset, and apparent differences in working memory capacity across individuals were attributable to individual differences in the implementation of chunking. Our results reveal a normative rationale for center-surround connectivity in working memory circuitry, call for re-evaluation of memory performance differences that have previously been attributed to differences in capacity, and support a more nuanced view of visual working memory capacity limitations: strategic tradeoff between storage capacity and memory precision through chunking contribute to flexible capacity limitations that include both discrete and continuous aspects.
fastBMA: Scalable Network Inference and Transitive Reduction
Authors: Hung Ling-Hong , Shi Kaiyuan , Wu Migao , Young William Chad , Raftery Adrian E. , Yeung Ka Yee
Published: January 2017

BACKGROUND:

Inferring genetic networks from genome-wide expression data is extremely demanding computationally. We have developed fastBMA, a distributed, parallel and scalable implementation of Bayesian model averaging (BMA) for this purpose. fastBMA also includes a novel and computationally efficient method for eliminating redundant indirect edges in the network.

FINDINGS:

We evaluated the performance of fastBMA on synthetic data and experimental genome-wide yeast and human datasets. When using a single CPU core, fastBMA is up to 100 times faster than the next fastest method, LASSO, with increased accuracy. It is a memory efficient, parallel and distributed application that scales to human genome wide expression data. A 10,000-gene regulation network can be obtained in a matter of hours using a 32-core cloud cluster.

CONCLUSIONS:

fastBMA is a significant improvement over its predecessor ScanBMA. It is orders of magnitude faster and more accurate than other fast network inference methods such as LASSO. The improved scalability allows it to calculate networks from genome scale data in a reasonable timeframe. The transitive reduction method can improve accuracy in denser networks. fastBMA is available as code (M.I.T. license) from GitHub (https://github.com/lhhunghimself/fastBMA), as part of the updated networkBMA Bioconductor package (https://www.bioconductor.org/packages/release/bioc/html/networkBMA.html) and as ready-to-deploy Docker images (https://hub.docker.com/r/biodepot/fastbma/).
Prognostic value of the MicroRNA‐29 family in multiple human cancers: A meta‐analysis and systematic review
Authors: Qi Yan , Huang Yalan , Pang Lijuan , Gu Wenyi , Wang Ning , Hu Jianming , Cui Xiaobin , Zhang Jun , Zhao Jin , Liu Chunxia , Zhang Wenjie , Zou Hong , Li Feng
Published: January 2017

MicroRNAs (miRNAs) in cancer development have attracted much attention in recent years. miR‐29 is known to critically affect cancer progression by functioning as a tumor suppressor. However, it may also act as an oncogene under certain situations. The prognostic value of the miR‐29 family in cancer progression is still under debate and reported results are inconsistent. Therefore, we reported here a meta‐analysis and systematic review to analyze the prognostic role of the miR‐29 family in cancer. We screened 20 published studies and calculated pooled hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) for overall survival (OS) or disease‐free survival/recurrence‐free survival (DFS/RFS). Our results showed that a low or absent expression of miR‐29 family was significantly associated with poor OS (HR, 1.57; 95%CI, 1.18‐2.08), and inferior to 5‐year DFS/RFS (HR, 1.89; 95%CI, 1.47‐2.44). Analysis of individual miR‐29 subtypes indicated that the low expression of miR‐29a/b/c subtypes correlated with poor 5‐year OS (miR‐29a: HR, 1.99; 95%CI, 1.41‐2.80; miR‐29b: HR, 1.60; 95%CI, 1.18‐2.17; miR‐29c: HR, 1.69; 95%CI, 1.00‐2.86), as well as poor 5‐year DFS/RFS (miR‐29b: HR, 1.70; 95%CI, 1.27‐2.27). Ethnicity analysis demonstrated Asian patients with low expression of miR‐29 were significantly correlated with poor OS (HR, 1.61; 95%CI, 1.16‐2.23) and 5‐year DFS/RFS (HR, 2.03; 95%CI, 1.50‐2.74). Taken together, our analysis indicates that the low expression of miR‐29 is associated with aggressiveness and poor prognosis of malignant neoplasms. More importantly, miR‐29 might serve as a key biomarker for predicting the recurrence and progression of human cancers.
Effects of electrical lesion of basolateral amygdala nucleus on rat anxiety‐like behaviour under acute, sub‐chronic, and chronic stresses
Authors: Ranjbar Hoda , Radahmadi Maryam , Reisi Parham , Alaei Hojjatallah
Published: January 2017

Stress contributes, as a risk factor, to such psychological disorders as anxiety. The effects of electrical lesions in the basolateral amygdala nucleus (BLA) were investigated on the locomotor activity and anxiety‐like behaviour in different stress durations. For this purpose, rats were randomly allocated to control, sham, and experimental groups, the latter including groups with and without BLA nucleus subjected to acute, sub‐chronic, and chronic stress conditions for 1, 7, and 21 days, respectively, applied 6 h/d. The induced anxiety behaviour was evaluated using the open field test (OFT) while other variables were measured. Findings revealed that sub‐chronic stress led to significantly reduced (P<.05) anxiety behaviours as measured by entries into and the time spent in the centre area while it also led to significant impairments in exploratory and locomotor activities, indicating intensified anxiety‐like behaviour. BLA lesion affected rat behaviour differently such that it significantly (P<.05) decreased fear under sub‐chronic and chronic stress conditions as evidenced by the subjects’ greater tendency to enter the centre area in the open field test and their increased number of rearing events (P<.01). However, BLA lesion led to no significant decrease in the locomotor activity of subjects exposed to sub‐chronic or chronic stress conditions as compared with those in similar groups but without BLA lesion. Finally, BLA lesion was found not only to decrease significantly (P<.01) adrenal gland and body weights, particularly under sub‐chronic stress, but also to play a critical role in modulating adrenal functions by decreasing adrenal gland weight, and thereby reducing depression‐like symptoms.
DNA metabarcoding reveals that 200‐μm‐size‐fractionated filtering is unable to discriminate between planktonic microbial and large eukaryotes
Authors: Liu Lemian , Liu Min , Wilkinson David M. , Chen Huihuang , Yu Xiaoqing , Yang Jun
Published: January 2017

Microeukaryotic plankton (0.2–200 μm) are critical components of aquatic ecosystems and key players in global ecological processes. High‐throughput sequencing is currently revolutionizing their study on an unprecedented scale. However, it is currently unclear whether we can accurately, effectively and quantitatively depict the microeukaryotic plankton communities using traditional size‐fractionated filtering combined with molecular methods. To address this, we analysed the eukaryotic plankton communities both with, and without, prefiltering with a 200 μm pore‐size sieve –by using SSU rDNA‐based high‐throughput sequencing on 16 samples with three replicates in each sample from two subtropical reservoirs sampled from January to October in 2013. We found that ~25% reads were classified as metazoan in both size groups. The species richness, alpha and beta diversity of plankton community and relative abundance of reads in 99.2% eukaryotic OTUs showed no significant changes after prefiltering with a 200 μm pore‐size sieve. We further found that both >0.2 μm and 0.2–200 μm eukaryotic plankton communities, especially the abundant plankton subcommunities, exhibited very similar, and synchronous, spatiotemporal patterns and processes associated with almost identical environmental drivers. The lack of an effect on community structure from prefiltering suggests that environmental DNA from larger metazoa is introduced into the smaller size class. Therefore, size‐fractionated filtering with 200 μm is insufficient to discriminate between the eukaryotic plankton size groups in metabarcoding approaches. Our results also highlight the importance of sequencing depth, and strict quality filtering of reads, when designing studies to characterize microeukaryotic plankton communities.