bluuebunny/crossref_metadata_2025 huggingface dataset:
Protocol Duodenal Graft Biopsies Aid Pancreas Graft Surveillance
Authors: Gunther Brockmann Jens , Butt Amir , AlHussaini Hussa F. , AlMana Hadeel , AlSaad Khaled , Al-Awwami Moheeb , Clemens Broering Dieter , Ali Tariq
Published: August 2018

Background.

Histological evaluation of the pancreas graft is usually done on demand resulting in significant delays. This analysis reports on endoscopic protocol duodenal graft biopsies at regular intervals to determine feasibility, safety, and monitoring benefits.

Methods.

Protocol duodenal graft biopsies in 27 consecutive pancreas transplants (10 simultaneous pancreas kidney [SPK], 17 pancreas after kidney [PAK]) with a follow-up of a minimum of 12 months were performed at days 14, 30, 90, 180, 360, 430. University of Pittsburgh Medical Center classification for intestinal rejection was used. C4d staining was performed when antibody-mediated rejection was suspected.

Results.

Overall patient and pancreas graft survival was 100% and 93% at a mean follow-up of 2.8 years. One hundred sixty-seven endoscopic biopsy procedures were performed in 27 grafts without any complication. Biopsies revealed rejection in 3 (30%) SPK recipients and in 15 (82%) of PAK recipients as early as 14 days posttransplant. Two patients underwent PAK retransplantation diagnosed with acute rejection at day 180. All except 1 recipient being treated for rejection, showed histological improvement following antirejection treatment. Following transient treatment success, a total of 3 pancreas grafts were lost for immunological reason. One loss was immediate despite antirejection treatment, 1 secondary to nonresolving rejection at 7 months and the third due to recurrent rejection 15 months posttransplantation. Additionally, biopsies detected vascular (venous thrombosis) and overimmunosuppression (cytomegalovirus infection) complications.

Conclusions.

Protocol graft duodenal biopsies detect complications after whole-organ pancreas transplantation, are useful in guiding therapy, and carry potential for improving outcome.
Clinical Relevance of a Balance Training Program on Liver Transplant Patients. A Randomized Controlled Trial
Authors: Moya-Nájera Diego , Moya-Herraiz Ángel , Gargallo Pedro , Calatayud Joaquin , Escrig-Sos Javier , Colado Juan C.
Published: August 2018

Background.

Although some studies have reported significant improvements in physical function and strength after training programs on liver transplant (LT) recipients, there is a lack of knowledge on how it affects in static and dynamic balance, being an important part of these participants’ tasks development. The aim of the study was to determine the effects of a 6-month multicomponent circuit training program on static and dynamic balance in LT participants.

Methods.

Fifty-four participants were randomized at 6 months after LT into 2 groups: exercise (EXER) group and control (CONTROL) group, with repeat testing at 6 (baseline) and 12 months after LT. The intervention consisted of a multicomponent training, including balance, strength, endurance, and flexibility training, with exercises arranged in a circuit setup and a moderate intensity with high perceived exertion. Training sessions were performed in the hospital facilities with qualified trainers. To determine differences over time between EXER and CONTROL, mixed-regression linear models with subject variable as random factor and variables of treatment duration, type, and interaction as predictors were used.

Results.

The EXER group showed significant differences (P < 0.05) compared with CONTROL in all variables of static and dynamic balance, hip strength (49% versus 13%), agility (−16% versus −1%), and flexibility (78% versus −26%). Adherence to the intervention was 94%, and 80% of the participants continued voluntarily training after the 6 months.

Conclusions.

This study demonstrated that a multicomponent circuit training program at a moderate intensity with high perceived exertion could reduce the probability of injuries because it improves balance on LT recipients.
Intra-abdominal Complications After Pediatric Kidney Transplantation: Incidence and Risk Factors
Authors: Taher Amir , Zhu Benjamin , Ma Sophia , Shun Albert , Durkan Anne Maria
Published: August 2018

Background.

The incidence and types of intra-abdominal complications after pediatric transplantation are not well established, and specific risk groups have not been clearly identified.

Methods.

A retrospective chart review of all pediatric transplant recipients between 1995 and 2016 was undertaken. Intra-abdominal complications were grouped into 4 categories: fluid collections, gastrointestinal, vascular, and urogenital. Donor, recipient, and transplant characteristics were evaluated using univariate and multivariate logistic regressions.

Results.

There were 146 transplants meeting the inclusion criteria. The mean follow-up time was 4.6 ± 3.7 years (range, 0.3–18 y). The mean weight at transplantation was 31.5 ± 16.5 kg (range, 9–78), with 24 (16%) recipients being <15 kg and 23% younger than 5 years. Thirty-four (23%) patients had previous abdominal surgery. There were 32 complications identified in 27 (18%) transplant recipients. Fluid collections requiring surgical drainage developed in 9 (6.2%), gastrointestinal surgical complications in 12 (8.2%), vascular complications in 5 (3.5%), and urogenital complications in 6 (4.1%). There were only 3 graft losses due to abdominal complications, all after renal vein thrombosis. Weight <15 kg at the time of transplant (P = 0.016), previous abdominal surgery (P = 0.047), and intraperitoneal surgical technique (P = 0.008) were risk factors in the univariate analysis using Cox regression models, whereas only weight <15 kg (P = 0.003) and previous abdominal surgery (P = 0.008) were retained in the multivariate analysis.

Conclusions.

Intraabdominal complications occur in almost 1 in 5 pediatric renal transplant recipients. Weight <15 kg and previous abdominal surgery are risk factors for developing such complications.
Proposal to emend Rules 50a and 50b of the International Code of Nomenclature of Prokaryotes
Authors: Oren Aharon , Garrity George
Published: August 2018

Rules 50a and 50b of the International Code of Nomenclature of Prokaryotes respectively regulate the elevation of a subspecies to the rank of a species and the lowering of a species to the rank of subspecies. The Code does not indicate that the resulting new names must be considered new combinations, as the cases described in Rules 50a and 50b are not covered by Rule 34a. Based on the rules of the Code, new combination events are applicable only at the identical rank, and therefore new combination events and new species/subspecies events are mutually exclusive. In spite of this there have been at least 44 cases in which the new names were described as comb. nov. during elevation in rank from subspecies to species and at least 30 such cases during lowering in rank from species to subspecies. To prevent confusion in the future we propose adding notes to Rules 50a and 50b to clarify the issue.
Excess body weight and age associated with the carriage of fluoroquinolone and third-generation cephalosporin resistance genes in commensal Escherichia coli from a cohort of urban Vietnamese children
Authors: Thi Quynh Nhi Le , Thanh Tuyen Ha , Duc Trung Pham , Do Hoang Nhu Tran , Duy Pham Thanh , Hao Chung The , Thi Thanh Nhan Nguyen , Vi Lu Lan , Thi Diem Tuyet Hoang , Thi Thuy Tien Tran , Van Vinh Chau Nguyen , Khanh Lam Phung , Thwaites Guy , Baker Stephen
Published: August 2018

Purpose. Antimicrobial-resistant bacterial infections in low- and middle-income countries (LMICs) are a well-established global health issue. We aimed to assess the prevalence of and epidemiological factors associated with the carriage of ciprofloxacin- and ceftriaxone-resistant Escherichia coli and associated resistance genes in a cohort of 498 healthy children residing in urban Vietnam.

Methodology. We cultured rectal swabs onto MacConkey agar supplemented with resistant concentrations of ciprofloxacin and ceftriaxone. Additionally, we screened meta-E. coli populations by conventional PCR to detect plasmid-mediated quinolone resistance (PMQR)- and extended-spectrum β-lactamase (ESBL)-encoding genes. We measured the associations between phenotypic/genotypic resistance and demographic characteristics using logistic regression.

Results/Key findings. Ciprofloxacin- and ceftriaxone-resistant E. coli were cultured from the faecal samples of 67.7 % (337/498) and 80.3 % (400/498) of children, respectively. The prevalence of any associated resistance marker in the individual samples was 86.7 % (432/498) for PMQR genes and 90.6 % (451/498) for β-lactamase genes. Overweight children were significantly more likely to carry qnr genes than children with lower weight-for-height z-scores [odds ratios (OR): 1.24; 95 % confidence interval (CI): 10.5–1.48 for each unit increase in weight for height; P=0.01]. Additionally, younger children were significantly more likely to carry ESBL CTX-M genes than older children (OR: 0.97, 95 % CI: 0.94–0.99 for each additional year, P=0.01).

Conclusion. The carriage of genotypic and phenotypic antimicrobial resistance is highly prevalent among E. coli in healthy children in the community in Vietnam. Future investigations on the carriage of antimicrobial resistant organisms in LMICs should focus on the progression of carriage from birth and structure of the microbiome in obesity.
Medical Nonadherence, Cannabis Use, and Renal Outcome in Systemic Lupus Erythematosis
Authors: Jalil Basmah A. , Qualls Clifford R. , Cabacungan Romy J. , Sibbitt Wilmer L. , Gibb James I. , Noronha Leonard E. , Fields Roderick A. , Emil N. Suzanne , Fangtham Monthida , Bankhurst Arthur D
Published: August 2018

Background/Objective

Non-adherence to recommended medical therapy has been associated with poorer outcomes in systemic lupus erythematosus (SLE). The present research investigated the association of medical non-adherence and cannabis use on renal outcomes of SLE.

Methods

This was a prospective 5-year longitudinal outcome study of 276 female SLE patients 30.4% who chronically used medical cannabis and 69.5% who did not. Outcomes were determined at 5 years after enrollment in the study.

Results

Cannabis use in SLE patients was associated with an increased prevalence of neuropsychiatric SLE (p<0.05), opioid analgesic use (p<0.01), cigarette smoking (p<0.001), and non-adherence to the medical regimen (non-cannabis: 3% non-adherence vs. cannabis use: 95% non-adherence, p<0.001). Within the 5-year period, the cannabis group demonstrated a 53% increase in mortality (p=0.12) and 127% increase in end-stage renal disease requiring dialysis (p<0.001). With logistic regression analysis adjusting for SLE disease activity (SLEDAI-2K), cannabis use was an independent predictor of end-stage renal disease: Odds ratio 2.65 (CI 1.32 – 5.32, p<0.01). Adjusting for SLE disease damage (SLICC/ACR-DI), cannabis use remained an independent predictor of end-stage renal disease: Odds ratio 2.0 (CI 1.26 – 6.23, p<0.01). With multivariable analysis adjusting for non-adherence, the effect of cannabis on end-stage renal disease could be largely attributed to an increase in non-adherence to medical therapy.

Conclusions

Non-adherence to recommended therapy and medical cannabis use are associated with a significant increase in the development of end-stage renal disease in SLE.
Seasonal synchronization of sleep timing in industrial and pre-industrial societies: the regulating role of Daylight Saving Time
Authors: Martin-Olalla Jose Maria
Published: August 2018

Did artificial light reshape human sleep/wake cycle? Most likely the answer is "yes". Did artificial light misalign the sleep/wake cycle in industrialized societies relative to the natural cycle of light and dark? For the average person ---that is, obviating the tail of the distributions--- the answer is probably not. Sleep timing in extratropical, industrial (data from eight national time use surveys) societies and Subtropical, pre-industrial societies (data from nine locations coming from seven previous reports) with and without access to artificial light finds in winter a remarkable accommodation with sunrise time along a wide range of angular distance to the Equator (0° to 55°). Within the two process model of sleep, results show sleep onset and sleep offset keep bound to each other by the homeostatic process, while the photoreceptive process aligns the phase of the sleep/wake cycle to winter sunrise. This results in a phase increasingly lagging with increasing latitude up to a delay of 2h at 55° latitude. In the summer season, the homeostatic process persists binding sleep onset to speep offset but Daylight Saving Time regulations in industrialized societies reduce the lag to 40min at 55° latitude. Sleep timing is then stationary with latitude.
Fitness Effects of Somatic Mutations Accumulating during Vegetative Growth
Authors: Cruzan Mitchell B. , Streisfeld Matthew A. , Schwoch Jaime A.
Published: August 2018

The unique life form of plants promotes the accumulation of somatic mutations that can be passed to offspring in the next generation, because the same meristem cells responsible for vegetative growth also generate gametes for sexual reproduction. However, little is known about the consequences of somatic mutation accumulation for offspring fitness. We evaluate the fitness effects of somatic mutations inMimulus guttatusby comparing progeny from self-pollinations made within the same flower (autogamy) to progeny from self-pollinations made between stems on the same plant (geitonogamy). The effects of somatic mutations are evident from this comparison, as autogamy leads to homozygosity of a proportion of somatic mutations, but progeny from geitonogamy remain heterozygous for mutations unique to each stem. In two different experiments, we find consistent fitness effects of somatic mutations from individual stems. Surprisingly, several progeny groups from autogamous crosses displayed increases in fitness compared to progeny from geitonogamy crosses, indicating that beneficial somatic mutations were prevalent in some stems. These results support the hypothesis that somatic mutations accumulate during vegetative growth, but they are filtered by different forms of selection that occur throughout development, resulting in the culling of expressed deleterious mutations and the retention of beneficial mutations.
Identification of negative BOLD responses using windkessel models
Authors: Valdés-Hernández Pedro A. , Bernal Byron , Moshkforoush Arash , Dunoyer Catalina , Khoo Hui Ming , Bosch-Bayard Jorge , von-Ellenrieder Nicolas , Gotman Jean , Riera Jorge J.
Published: August 2018

Alongside positive BOLD responses (PBR), a variety of negative BOLD responses (NBR) with distinct underlying mechanisms also occur. We identify five mechanisms of NBR: i) local/lateral/contralateral inhibition (LCI), ii) neuronal disruption of network activity (NDA), iii) altered balance of neuro-metabolic/vascular couplings (ANC), iv) arterial blood stealing (ABS), and v) venous blood backpressure (VBB). Detecting and classifying these mechanisms from BOLD signals is pivotal in understanding normal/pathological brain functions. This requires models and parameters with anatomical/functional interpretation that furnish the understanding of how these mechanisms are fingerprinted by their BOLD responses. Here, we used a windkessel model with viscoelastic compliance as well as dynamics of both neuronal and tissue/blood O2 to investigate the generation, detection, classification and interpretation of the BOLD hemodynamic response functions (HRF) of above mechanisms. Firstly, we evaluated the use of the general linear model to detect simulated NBRs. Secondly, we tested the ability of a machine learning classifier, built from a simulated ensemble of HRFs, to predict the mechanism underlying a new HRF. Crossvalidation indicates NDA and ANC can accurately be classified solely from fMRI BOLD signals; while LCI, ABS and VBB might require additional imaging modalities. Thirdly, we demonstrated that estimators of the model parameters determinant in the NBRs formation are accurate, and precise to certain resolutions. Finally, we successfully applied our detection/classification/estimation methodology to EEG-fMRI data in a clinical situation where several of these mechanisms could coexist. We believe that the proper identification and interpretation of NBR mechanisms have important clinical and cognitive implications in fMRI studies.
SonHi-C: a set of non-procedural approaches for predicting 3D genome organization from Hi-C data
Authors: MacKay Kimberly , Carlsson Mats , Kusalik Anthony
Published: August 2018

1

Background

Many computational methods have been developed that leverage the results from biological experiments (such as Hi-C) to infer the 3D organization of the genome. Formally, this is referred to as the 3D genome reconstruction problem (3D-GRP). None of the existing methods for solving the 3D-GRP have utilized a non-procedural programming approach (such as constraint programming or integer programming) despite the established advantages and successful applications of such approaches for predicting the 3D structure of other biomolecules. Our objective was to develop a set of mathematical models and corresponding non-procedural implementations for solving the 3D-GRP to realize the same advantages.

Results

We present a set of non-procedural approaches for predicting 3D genome organization from Hi-C data (collectively referred to as SonHi-C and pronounced “sonic”). Specifically, this set is comprised of three mathematical models based on constraint programming (CP), graph matching (GM) and integer programming (IP). All of the mathematical models were implemented using non-procedural languages and tested with Hi-C data from Schizosaccharomyces pombe (fission yeast). The CP implementation could not optimally solve the problem posed by the fission yeast data after several days of execution time. The GM and IP implementations were able to predict a 3D model of the fission yeast genome in 1.088 and 294.44 seconds, respectively. These 3D models were then biologically validated through literature search which verified that the predictions were able to recapitulate key documented features of the yeast genome.

Conclusions

Overall, the mathematical models and programs developed here demonstrate the power of non-procedural programming and graph theoretic techniques for quickly and accurately modelling the 3D genome from Hi-C data. Additionally, they highlight the practical differences observed when differing non-procedural approaches are utilized to solve the 3D-GRP.
A Bacterial Expression Vector Archive(BEVA) for flexible modular assembly of Golden Gate-compatible vectors
Authors: Geddes Barney A. , Mendoza-Suárez Marcela A. , Poole Philip S.
Published: August 2018

We present a Bacterial Expression Vector Archive (BEVA) for the modular assembly of bacterial vectors compatible with both traditional and Golden Gate cloning, utilizing the Type IIS restriction enzyme Esp3I. Ideal for synthetic biology and other applications, this modular system allows a rapid, low-cost assembly of new vectors tailored to specific tasks. To demonstrate the potential of the system three example vectors were constructed and tested. Golden Gate level 1 vectors; pOGG024, with a broad-host range and high copy number was used for gene expression in laboratory-culturedRhizobium leguminosarum, and pOGG026, with a broad-host range a lower copy number and excellent stability, even in the absence of antibiotic selection. The application of pOGG026 is demonstrated in environmental samples by bacterial gene expression in nitrogen-fixing nodules on pea plants roots formed byR. leguminosarum. Finally, the level 2 cloning vector pOGG216 is a broad-host range, medium copy number, for which we demonstrate an application by constructing a dual reporter plasmid expressing green and red fluorescent proteins.

IMPORTANCE

Modular assembly is powerful as it allows easy combining of different components from a library of parts. In designing a modular vector assembly system, the key constituent parts (and modules) are; an origin of plasmid replication, antibiotic resistance marker(s), cloning site(s), together with additional accessory modules as required. In an ideal vector, the size of each module would be minimized, and this we have addressed. We have designed such a vector assembly system by utilizing the Type IIS restriction enzyme Esp3I and have demonstrated its use for Golden Gate cloning inEscherichia coli. An important attribute of this modular vector assembly is that using the principles outlined here, new modules for specific applications, e.g. origin of replication for plasmids in other bacteria, can easily be designed. It is hoped that this vector construction system will be expanded by the scientific community over time by creation of novel modules through an open source approach.
Droplet rather than Aerosol Mediated Dispersion is the Primary Mechanism of Bacterial transmission from Contaminated Hand Washing Sink Traps
Authors: Kotay Shireen , Donlan Rodney M. , Ganim Christine , Barry Katie , Christensen Bryan E. , Mathers Amy J.
Published: August 2018

An alarming rise in hospital outbreaks implicating hand-washing sinks has led to widespread acknowledgement that sinks are a major reservoir of antibiotic resistant pathogens in patient-care areas. An earlier study using a GFP-expressing Escherichia coli (GFP-E. coli) as a model organism demonstrated dispersal from drain biofilm in contaminated sinks. The present study further characterizes the dispersal of microorganisms from contaminated sinks. Replicate hand-washing sinks were inoculated with GFP-E. coli, and dispersion was measured using qualitative (settle plates) and quantitative (air sampling) methods. Dispersal caused by faucet water was captured with settle plates and air sampling methods when bacteria were present on the drain. In contrast, no dispersal was captured without or in between faucet events amending earlier theory that bacteria aerosolize from P-trap and disperse. Numbers of dispersed GFP-E. coli diminished substantially within 30 minutes after faucet usage, suggesting that the organisms were associated with larger droplet-sized particles that are not suspended in the air for long periods.

IMPORTANCE

Among the possible environmental reservoirs in a patient care environment, sink drains are increasingly recognized as potential reservoir of multidrug resistant healthcare-associated pathogens to hospitalized patients. With increasing antimicrobial resistance limiting therapeutic options for patients, better understanding of how pathogens disseminate from sink drains is urgently needed. Once this knowledge gap has decreased, interventions can be engineered to decrease or eliminate transmission from hospital sink drains to patients. The current study further defines the mechanisms of transmission for bacteria colonizing sink drains.
Limits to anatomical accuracy of diffusion tractography using modern approaches
Authors: Schilling Kurt G , Nath Vishwesh , Hansen Colin , Parvathaneni Prasanna , Blaber Justin , Gao Yurui , Neher Peter , Aydogan Dogu Baran , Shi Yonggang , Ocampo-Pineda Mario , Schiavi Simona , Daducci Alessandro , Girard Gabriel , Barakovic Muhamed , Rafael-Patino Jonathan , Romascano David , Rensonnet Gaёtan , Pizzolato Marco , Bates Alice , Fischi Elda , Thiran Jean-Philippe , Canales-Rodríguez Erick J. , Huang Chao , Zhu Hongtu , Zhong Liming , Cabeen Ryan , Toga Arthur W , Rheault Francois , Theaud Guillaume , Houde Jean-Christophe , Sidhu Jasmeen , Chamberland Maxime , Westin Carl-Fredrik , Dyrby Tim B. , Verma Ragini , Rathi Yogesh , Irfanoglu M Okan , Thomas Cibu , Pierpaoli Carlo , Descoteaux Maxime , Anderson Adam W , Landman Bennett A
Published: August 2018

Diffusion MRI fiber tractography is widely used to probe the structural connectivity of thebrain, with a range of applications in both clinical and basic neuroscience. Despite widespread use, tractography has well-known pitfalls that limits the anatomical accuracy of this technique. Numerous modern methods have been developed to address these shortcomings through advances in acquisition, modeling, and computation. To test whether these advances improve tractography accuracy, we organized the ISBI 2018 3D Validation of Tractography with Experimental MRI (3D-VoTEM) challenge. We made available three unique independent tractography validation datasets – a physical phantom and two ex vivo brain specimens - resulting in 176 distinct submissions from 9 research groups. By comparing results over a wide range of fiber complexities and algorithmic strategies, this challenge provides a more comprehensive assessment of tractography’s inherent limitations than has been reported previously. The central results were consistent across all sub-challenges in that, despite advances in tractography methods, the anatomical accuracy of tractography has not dramatically improved in recent years. Taken together, our results independently confirm findings from decades of tractography validation studies, demonstrate inherent limitations in reconstructing white matter pathways using diffusion MRI data alone, and highlight the need for alternative or combinatorial strategies to accurately map the fiber pathways of the brain.
Identification of candidate genes underlying nodulation-specific phenotypes in Medicago truncotula through integration of genome-wide association studies and co-expression networks
Authors: Michno Jean-Michel , Burghardt Liana T. , Liu Junqi , Jeffers Joseph R. , Tiffin Peter , Stupar Robert M. , Myers Chad L.
Published: August 2018

Genome-wide association studies (GWAS) have proven to be a valuable approach for identifying genetic intervals associated with phenotypic variation in Medicago truncatula. These intervals can vary in size, depending on the historical local recombination near each significant interval. Typically, significant intervals span numerous gene models, limiting the ability to resolve high-confidence candidate genes underlying the trait of interest. Additional genomic data, including gene co-expression networks, can be combined with the genetic mapping information to successfully identify candidate genes. Co-expression network analysis provides information about the functional relationships of each gene through its similarity of expression patterns to other well-defined clusters of genes. In this study, we integrated data from GWAS and co-expression networks to pinpoint candidate genes that may be associated with nodule-related phenotypes in Medicago truncatula. We further investigated a subset of these genes and confirmed that several had existing evidence linking them nodulation, including MEDTR2G101090 (PEN3-like), a previously validated gene associated with nodule number.
Randomized lasso associates freshwater lake-system specific bacterial taxa with heterotrophic production through flow cytometry
Authors: Rubbens Peter , Schmidt Marian L. , Props Ruben , Biddanda Bopaiah A. , Boon Nico , Waegeman Willem , Denef Vincent J.
Published: August 2018

High-(HNA) and low-nucleic acid (LNA) bacteria are two operational groups identified by flow cytometry (FCM) in aquatic systems. HNA cell density often correlates strongly with heterotrophic production, while LNA cell density does not. However, which taxa are specifically associated with these groups, and by extension, productivity has remained elusive. Here, we addressed this knowledge gap by using a machine learning-based variable selection approach that integrated FCM and 16S rRNA gene sequencing data collected from 14 freshwater lakes spanning a broad range in physicochemical conditions. There was a strong association between bacterial heterotrophic production and HNA absolute cell abundances (R2= 0.65), but not with the more abundant LNA cells. This solidifies findings, mainly from marine systems, that HNA and LNA could be considered separate functional groups, the former contributing a disproportionately large share of carbon cycling. Taxa selected by the models could predict HNA and LNA absolute cell abundances at all taxonomic levels, with the highest performance at the OTU level. Selected OTUs ranged from low to high relative abundance and were mostly lake system-specific (89.5%-99.2%). A subset of selected OTUs was associated with both LNA and HNA groups (12.5%-33.3%) suggesting either phenotypic plasticity or within-OTU genetic and physiological heterogeneity. These findings may lead to the identification of systems-specific putative ecological indicators for heterotrophic productivity. Generally, our approach allows for the association of OTUs with specific functional groups in diverse ecosystems in order to improve our understanding of (microbial) biodiversity-ecosystem functioning relationships.

Importance

A major goal in microbial ecology is to understand how microbial community structure influences ecosystem functioning. Research is limited by the ability to readily culture most bacteria present in the environment and the difference in bacterial physiologyin situcompared to in laboratory culture. Various methods to directly associate bacterial taxa to functional groups in the environment are being developed. In this study, we applied machine learning methods to relate taxonomic data obtained from marker gene surveys to functional groups identified by flow cytometry. This allowed us to identify the taxa that are associated with heterotrophic productivity in freshwater lakes and indicated that the key contributors were highly system-specific, regularly rare members of the community, and that some could switch between being low and high contributors. Our approach provides a promising framework to identify taxa that contribute to ecosystem functioning and can be further developed to explore microbial contributions beyond heterotrophic production.
The SHAPE of logistic growth shows that serial passaging biases fixation probability
Authors: Dench Jonathan
Published: August 2018

The forward time simulation tool rSHAPE (R-package for Simulated Haploid Asexual Population Evolution) was designed to complement the theoretical and empirical study of evolution. Included with rSHAPE are functions to programmatically build, run, and initially process results of an evolutionary experiment defined by the range of experimental conditions. As experimental evolution often studies both the emergence and fate ofde novomutants, I validated rSHAPE by confirming its ability to replicate seminal theoretical expectations concerning changes in fitness through time and the fixation probability of mutants. As an example of how rSHAPE can support both theoretical and empirical research, I applied rSHAPE to study how the laboratory protocol of serial passaging, common in microbial experimental evolution, affects the fixation probability ofde novomutants. Unlike related theoretical work which modelled growth as effectively exponential (Wahlet al., 2002), this study considered populations experiencing logistic growth which is common to microbes undergoing serial passaging. In contrast to exponential growth, when a population undergoes logistic growth the probability of a mutant arising and eventually fixing depends upon when a mutant arises during a growth phase. Users can download software and documentation for rSHAPE through CRAN athttps://cran.r-project.org/web/packages/rSHAPE/index.html, or via GitHub athttps://www.github.com/Jdench/SHAPE_library/.
CCCP experimental evolution ofEscherichia coliselects for mutations that increase EmrA activity or that downregulate other PMF-driven drug efflux pumps
Authors: Griffith Jessie M. , Basting Preston J. , Bischof Katarina M. , Wrona Erintrude P. , Kunka Karina S. , Tancredi Anna C. , Moore Jeremy P. , Hyman Miriam R. L. , Slonczewski Joan L.
Published: August 2018

Experimental evolution was conducted withEscherichia coliK-12 W3110 in the presence of carbonyl cyanide m-chlorophenylhydrazone (CCCP), an uncoupler of the proton motive force (PMF). Cultures were serially diluted daily 1:100 in broth medium containing 20-150 μM CCCP at pH 6.5 or at pH 8.0. After 1,000 generations, all populations showed 5- to 10-fold increase in CCCP resistance. Sequenced isolates showed mutations inemrABor in its negative repressormprA; the EmrAB-TolC multidrug efflux pump confers resistance to CCCP and nalidixic acid. Deletion ofemrAabolished the CCCP resistance of these strains. One CCCP-evolved isolate lackedemrAormprAmutations; this strain (C-B11-1) showed mutations in drug efflux regulatorscecR(ybiH) (upregulates drug pumps YbhG and YbhFSR) andgadE(upregulates drug pumpmdtEF). AcecR∷kanRdeletion conferred partial resistance to CCCP. A later evolved descendant of the C-B11 population showed mutations inybhR(MDR efflux). Another isolate showedacrB(MDR efflux pump). TheacrBisolate was sensitive to chloramphenicol and tetracycline, which are effluxed by AcrAB. Other mutant genes in CCCP-evolved strains includeadhE(alcohol dehydrogenase),rng(ribonuclease G), andcyaA(adenylate cyclase). Overall, experimental evolution revealed a CCCP fitness advantage for mutations increasing its own efflux via EmrA; and for mutations that may decrease proton-driven pumps that efflux other drugs not present (cecR, gadE, acrB, ybhR). These results are consistent with our previous report of drug sensitivity associated with evolved tolerance to a partial uncoupler (benzoate or salicylate).

IMPORTANCE

The genetic responses of bacteria to depletion of proton motive force, and their effects on drug resistance, are poorly understood. Our evolution experiment reveals genetic mechanisms of adaptation to the PMF uncoupler CCCP, including selection for and against various multidrug efflux pumps. The results have implications for our understanding of the gut microbiome, which experiences high levels of organic acids that decrease PMF. Organic acid uncouplers may select against multidrug resistance in evolving populations of enteric bacteria.
Keystone mutualists can facilitate transition between alternative ecosystem states in the soil
Authors: Duhamel Marie , Wan Joe , Bogar Laura M. , Segnitz R. Max , Duncritts Nora C. , Peay Kabir G.
Published: August 2018

Symbioses between plants and microbial organisms can fundamentally alter the structure of ecosystems, from their species diversity to rates of nutrient cycling. Yet, many aspects of how differences in the prevalence of microbial symbioses arise are unclear. This is a key knowledge gap, as if co-variation in plant and microbial distributions are primarily determined by extrinsic abiotic factors then symbioses should exert little independent control over ecosystems. To examine the potential for alternative symbiotic communities to arise under similar conditions we examined biogeochemical cycling and microbial community structure in a coastal landscape where historical patterns of vegetation transition are known, allowing us to eliminate abiotic determinism. We found that alternative states in microbial community structure and ecosystem processes emerged under different plant species. Greenhouse studies further demonstrated that plant selection of symbiotic microbes is central to emergence of these alternative states and occurs independent of soil abiotic conditions. Moreover, we provide evidence that transition between states may be highly dependent on the presence of a small set of ruderal symbionts that are rare in mature systems but may act as keystone mutualists. Because differences between these alternative states can be directly linked to plant-microbe symbioses, independent of initial conditions, our results suggesting that biotic feedbacks between keystone symbiotic microbes and plants play a foundational role in the diversity and function of soils.
eTumorRisk, an algorithm predicts cancer risk based on comutated gene networks in an individual’s germline genome
Authors: Zou Jinfeng , Wang Edwin
Published: August 2018

Early cancer detection has potentials to reduce cancer burden. A prior identification of the high-risk population of cancer will facilitate cancer early detection. Traditionally, cancer predisposition genes such as BRCA1/2 have been used for identifying high-risk population of developing breast and ovarian cancers. However, such high-risk genes have only a few. Moreover, the complexity of cancer hints multiple genes involved but also prevents from identifying such predictors for predicting high-risk subpopulation. Therefore, we asked if the germline genomes could be used to identify high-risk cancer population. So far, none of such predictive models has been developed. Here, by analyzing of the germline genomes of 3,090 cancer patients representing 12 common cancer types and 25,701 non-cancer individuals, we discovered significantly differential co-mutated gene pairs between cancer and non-cancer groups, and even between cancer types. Based on these findings, we developed a network-based algorithm, eTumorRisk, which enables to predict individuals’ cancer risk of six genetic-dominant cancers including breast, colon, brain, leukemia, ovarian and endometrial cancers with the prediction accuracies of 74.1-91.7% and have 1-3 false-negatives out of the validating samples (n=14,701). The eTumorRisk which has a very low false-negative rate might be useful in screening of general population for identifying high-risk cancer population.
Effective Machine-Learning Assembly For Next-Generation Sequencing With Very Low Coverage
Authors: Ranjard Louis , Wong Thomas K. F. , Rodrigo Allen G.
Published: August 2018

In short-read DNA sequencing experiments, the read coverage is a key parameter to successfully assemble the reads and reconstruct the sequence of the input DNA. When coverage is very low, the original sequence reconstruction from the reads can be difficult because of the occurrence of uncovered gaps. Reference guided assembly can then improve these assemblies. However, when the available reference is phylogenetically distant from the sequencing reads, the mapping rate of the reads can be extremely low. Some recent improvements in read mapping approaches aim at modifying the reference according to the reads dynamically. Such approaches can significantly improve the alignment rate of the reads onto distant references but the processing of insertions and deletions remains challenging. Here, we introduce a dynamic programming algorithm to update the reference sequence according to previously aligned reads. Substitutions, insertions and deletions are performed in the reference sequence dynamically. We evaluate this approach to assemble a western-grey kangaroo mitochondrial amplicon. Our results show that more reads can be aligned and that this method produces assemblies of length comparable to the truth while limiting error rate when classic approaches fail to recover the correct length. Our method allows us to assemble the first full mitochondrial genome for the western-grey kangaroo. Finally, we discuss how the core algorithm of this method could be improved and combined with other approaches to analyse larger genomic sequences.
A new schizophrenia model: immune activation is associated with induction of the tryptophan catabolite pathway and increased eotaxin levels which together determine memory impairments and schizophrenia symptom dimensions
Authors: Sirivichayakul Sunee , Kanchanatawan Buranee , Thika Supaksorn , Carvalho André F. , Maes Michael
Published: August 2018

Objective

Recently, we reported that stable-phase schizophrenia is characterized by two interrelated symptom dimensions: PHEMN (psychotic, hostility, excitation, mannerism and negative symptoms); and DAPS (depressive, anxiety and physio-somatic symptoms) and that Major Neuro-Cognitive psychosis (MNP) is the full blown phenotype of schizophrenia (largely overlapping with deficit schizophrenia). Herein we examined the effects of immune activation in association with tryptophan catabolite (TRYCAT) patterning and memory disorders on PHEMN/DAPS dimensions and MNP.

Method

Serum levels of macrophage inflammatory protein-1 (MIP-1), soluble interleukin (IL)-1 receptor antagonist (sIL-1RA), IL-10, eotaxin, IgA/IgM responses to TRYCATs, and Consortium to Establish a Registry for Alzheimer’s disease (CERAD) tests were assessed in 40 controls and 80 schizophrenia patients.

Results

Schizophrenia and MNP were predicted by significantly increased levels of IL-10, eotaxin and TRYCATs. A large part of the variance in both PHEMN/DAPS symptom dimensions (42.8%) was explained by cytokine levels and TRYCATs combined. The MTP+sTL-1R A+IL-10 composite score and eotaxin explained each around 19% of the variance in symptom dimensions, and approximately 18% of memory deficits. Moreover, MIP+sIL-1RA+IL-10 was significantly associated with elevations in picolinic acid, xanthurenic acid and 3-OH-kynurenine. Partial Least Squares path modeling shows that the highly significant effects of MIP+sIL-1RA+IL-10 on symptomatology are mediated by the effects of noxious TRYCATs on memory deficits.

Conclusions

Current findings indicate that in schizophrenia, immune activation may underpin activation of indoleamine-2,3-dioxygenase and kynurenine monooxygenase, while impairments in episodic and semantic memory may be caused by the neurotoxic effects of TRYCATs and eotaxin. The combined effects of immune activation, eotaxin and memory defects determine to a large extent PHEMN/DAPS symptoms and the MNP phenotype. These findings indicate that schizophrenia phenomenology is largely mediated by multiple neuro-immune pathways and that immune activation, increased production of eotaxin and neurotoxic TRYCATs (picolinic acid, xanthurenic acid and 3-HO-kynurenine) are new drug targets in schizophrenia and MNP.
Glycine promotes longevity inCaenorhabditis elegansin a methionine cycle-dependent fashion
Authors: Liu Yasmine J. , Janssens Georges E. , Kamble Rashmi , Gao Arwen W. , Jongejan Aldo , Weeghel Michel van , MacInnes Alyson W. , Houtkooper Riekelt H.
Published: August 2018

The deregulation of metabolism is a hallmark of aging. As such, changes in the expression of metabolic genes and the profiles of amino acid levels are features associated with aging animals. We previously reported that the levels of most amino acids decline with age inCaenorhabditis elegans (C. elegans).Glycine, in contrast, substantially accumulates in agingC. elegans. In this study we show that this is coupled to a decrease in gene expression of enzymes important for glycine catabolism. We further show that supplementation of glycine significantly prolongsC. eleganslifespan and ameliorates specific transcriptional changes that are associated with aging. Glycine feeds into the methionine cycle. We find that mutations in components of this cycle, methionine synthase(metr-1)and S-adenosylmethionine synthetase(sams-1), completely abrogate glycine-induced lifespan extension. Strikingly, the beneficial effects of glycine supplementation are conserved when we supplement with serine, also driving the methionine cycle. RNA sequencing of serine- and glycine-supplemented worms reveals similar transcriptional profiles including widespread gene suppression. Taken together, these data uncover a novel role of glycine in the deceleration of aging through its function in the methionine cycle.

Author summary

There are a growing number of studies showing that amino acids function as signal metabolites that influence aging and health. Although contemporary -OMICs studies have uncovered various associations between metabolite levels and aging, in many cases the directionality of the relationships is unclear. In a recent metabolomics study, we found that glycine accumulates in agedC. eleganswhile other amino acids decrease. The present study shows that glycine supplementation prolongs longevity and drives a genome-wide inhibition effect onC. elegansgene expression. Glycine as a one-carbon donor fuels the methyl pool of one-carbon metabolism composed of folates and methionine cycle. We find that glycine-mediated longevity effect is fully dependent on methionine cycle, and that all of these observations are conserved with supplementation of the other one-carbon amino acid, serine. These results provide a novel role for glycine as a promoter of longevity and bring new insight into the role of one-carbon amino acids in the regulation of aging that may ultimately be beneficial for humans.
Excess of rare missense variants in hearing loss genes in sporadic Meniere disease
Authors: Gallego-Martinez Alvaro , Requena Teresa , Roman-Naranjo Pablo , Lopez-Escamez Jose A. ,   Meniere Disease Consortium (MeDiC)
Published: August 2018

Meniere’s disease (MD) is a clinical spectrum of rare disorders characterized by vertigo attacks, associated with sensorineural hearing loss (SNHL) and tinnitus involving low to medium frequencies. Although it shows familial aggregation with incomplete phenotypic forms and variable expressivity, most cases are considered sporadic. The aim of this study was to investigate the burden for rare variation in SNHL genes in patients with sporadic MD.

We conducted a targeted-sequencing study including SNHL and familial MD genes in 890 MD patients to compare the frequency of rare variants in cases using three independent public datasets as controls.

Patients with sporadic MD showed a significant enrichment of missense variants in SNHL genes that was not found in the controls. The list of genes includesGJB2, USH1G, SLC26A4, ESRRBandCLDN14. A rare synonymous variant with unknown significance was found in theMARVELD2gene in several unrelated patients with MD.

There is a burden of rare variation in certain SNHL genes in sporadic MD. Furthermore, the physical interaction of specific gene variants at protein level can explain the additive effect of rare variants in different genes in MD. This study will contribute to design a gene panel for the genetic diagnosis of MD.
Petite Integration Factor 1 (PIF1) helicase deficiency increases weight gain in Western diet-fed female mice without increased inflammatory markers or decreased glucose clearance
Authors: Belmonte Frances R. , Dedousis Nikolaos , Sipula Ian , Desai Nikita A. , Singhi Aatur D. , Chu Yanxia , Zhang Yingze , Bannwarth Sylvie , Paquis-Flucklinger Véronique , Harrington Lea , Jurczak Michael J. , O’Doherty Robert M. , Kaufman Brett A.
Published: August 2018

Petite Integration Factor 1 (PIF1) is a multifunctional helicase present in nuclei and mitochondria. PIF1 knock out (KO) mice exhibit accelerated weight gain and decreased wheel running on a normal chow diet. In the current study, we investigated whether Pif1 removal alters whole body metabolism in response to weight gain. PIF1 KO and wild type (WT) C57BL/6J mice were fed a Western diet (WD) rich in fat and carbohydrates before evaluation of their metabolic phenotype. Compared with weight gain-resistant WT female mice, WD-fed PIF1 KO females, but not males, showed accelerated adipose deposition, decreased locomotor activity, and reduced whole-body energy expenditure without increased dietary intake. Surprisingly, PIF1 KO females were protected against obesity-induced alterations in fasting blood glucose and glucose clearance. WD-fed PIF1 KO females developed mild hepatic steatosis and associated changes in liver gene expression that were absent in weight-matched, WD-fed female controls, linking hepatic steatosis to Pif1 ablation rather than increased body weight. WD-fed PIF1 KO females also showed decreased gene expression of inflammatory markers in adipose tissue. Collectively, these data separated weight gain from inflammation and impaired glucose homeostasis. They also support a role for Pif1 in weight gain resistance and liver metabolic dysregulation during nutrient stress.