bluuebunny/crossref_metadata_2025 huggingface dataset:
Evolution and function of tandem repeats in the major surface protein 1a of the ehrlichial pathogenAnaplasma marginale
Authors: de la Fuente José , Garcia-Garcia Jose C. , Blouin Edmour F. , Rodríguez Sergio D. , García Migel A. , Kocan Katherine M.
Published: March 2018

The major surface protein (MSP) 1a of the ehrlichial cattle pathogenAnaplasma marginale, encoded by the single-copy genemsp1α, has been shown to have a neutralization-sensitive epitope and to be an adhesin for bovine erythrocytes and tick cells.msp1αhas been found to be a stable genetic marker for the identification of geographic isolates ofA. marginalethroughout development in acutely and persistently infected cattle and in ticks. The molecular weight of MSP1a varies among geographic isolates ofA. marginalebecause of a varying number of tandemly repeated peptides of 28–29 amino acids. Variation in the sequence of the tandem repeats occurs within and among isolates, and may have resulted from evolutionary pressures exerted by ligand–receptor and host–parasite interactions. These repeated sequences include markers for tick transmissibility that may be important in the identification of ehrlichial pathogens because they may influence control strategies and the design of subunit vaccines.
Latin as a Common Language: The Coherence of Lorenzo Valla’s Humanist Program
Authors: Nauta Lodi
Published: March 2018

In his critique of the language and thought of the Scholastics, Lorenzo Valla contrasts classical Latin as a natural, common language to the so-called artificial, technical, and unnatural language of his opponents. He famously champions Quintilian’s view that one should follow common linguistic usage. Scholars, however, have disagreed about the precise interpretation of these qualifications of Latin. This article argues that, depending on the historical, rhetorical, and argumentative contexts, Valla uses notions such as common and natural in different ways to suit different purposes. Such a contextualized reading has repercussions for an evaluation of the coherence of Valla’s humanist program.
ASGART: fast and parallel genome scale segmental duplications mapping
Authors: Delehelle Franklin , Cussat-Blanc Sylvain , Alliot Jean-Marc , Luga Hervé , Balaresque Patricia
Published: March 2018

Motivation

Segmental Duplications (SDs) are DNA fragments longer than 1 kbp, distributed within and between chromosomes and sharing more than 90% identity. Although they hold a significant role in genomic fluidity and adaptability, many key questions about their intrinsic characteristics and mutability remain unsolved due to the persistent difficulty of sequencing highly duplicated genomic regions. The recent development of long and linked-read NGS technologies will increase the need to search for SDs in genomes newly sequenced with these technics. The main limitation of SD analysis will soon be the availability of efficient detection software, to retrieve and compare SD genomic component between species or lineages.

Results

In this paper, we present the open-source ASGART, ‘A Segmental duplications Gathering And Refining Tool’, developed to search for segmental duplications (SDs) in any assembled sequence. We have tested and benchmarked ASGART on five models organisms. Our results demonstrate ASGART’s ability to extract SDs from any genome-wide sequence, regardless of genomic size or organizational complexity and quicker than any other software available.

Availability and implementation

The online version of ASGART is available at http://asgart.irit.fr. The source code of ASGART is available both on the ASGART website and at https://github.com/delehef/asgart.

Supplementary information

Supplementary data are available at Bioinformatics online.
Relationships Between Tau and Glucose Metabolism Reflect Alzheimer’s Disease Pathology in Cognitively Normal Older Adults
Authors: Adams Jenna N , Lockhart Samuel N , Li Lexin , Jagust William J
Published: March 2018

Tau is associated with hypometabolism in patients with Alzheimer’s disease. In normal aging, the association between tau and glucose metabolism is not fully characterized. We used [18F] AV-1451, [18F] Fluorodeoxyglucose, and [11C] Pittsburgh Compound-B (PiB) PET to measure associations between tau and glucose metabolism in cognitively normal older adults (N = 49). Participants were divided into amyloid-negative (PiB–, n = 28) and amyloid-positive (PiB+, n = 21) groups to determine effects of amyloid-β. We assessed both local and across-brain regional tau–glucose metabolism associations separately in PiB–/PiB+ groups using correlation matrices and sparse canonical correlations. Relationships between tau and glucose metabolism differed by amyloid status, and were primarily spatially distinct. In PiB– subjects, tau was associated with broad regions of increased glucose metabolism. In PiB+ subjects, medial temporal lobe tau was associated with widespread hypometabolism, while tau outside of the medial temporal lobe was associated with decreased and increased glucose metabolism. We further found that regions with earlier tau spread were associated with stronger negative correlations with glucose metabolism. Our findings indicate that in normal aging, low levels of tau are associated with a phase of increased metabolism, while high levels of tau in the presence of amyloid-β are associated with hypometabolism at downstream sites.
Systematic review: methodological flaws in racial/ethnic reporting for gastroesophageal reflux disease
Authors: Craven M R , Kia L , O’Dwyer L C , Stern E , Taft T H , Keefer L
Published: March 2018

Health care disparities affecting the care of multiple disease groups are of growing concern internationally. Research guidelines, governmental institutions, and scientific journals have attempted to minimize disparities through policies regarding the collection and reporting of racial/ethnic data. One area where shortcomings remain is in gastroesophageal reflux disease (GERD). This systematic review, which adheres to the PRISMA statement, focuses on characterizing existing methodological weaknesses in research focusing on studies regarding the assessment, prevalence, treatment, and outcomes of GERD patients. Search terms included GERD and typical symptoms of GERD in ethnic groups or minorities. We reviewed 62 articles. The majority of studies did not report the race/ethnicity of all participants, and among those who did, very few followed accepted guidelines. While there were diverse participants, there was also diversity in the manner in which groups were labeled, making comparisons difficult. There appeared to be a disparity with respect to countries reporting race/ethnicity, with certain countries more likely to report this variable. Samples overwhelmingly consisted of the study country's majority population. The majority of studies justified the use of race/ethnicity as a study variable and investigated conceptually related factors such as socioeconomic status and environment. Yet, many studies wrote as if race/ethnicity reflected biological differences. Despite recommendations, it appears that GERD researchers around the world struggle with the appropriate and standard way to include, collect, report, and discuss race/ethnicity. Recommendations on ways to address these issues are included with the goal of preventing and identifying health care disparities.
New Opioid Analgesic Approvals and Outpatient Utilization of Opioid Analgesics in the United States, 1997 through 2015
Authors: Chai Grace , Xu Jing , Osterhout James , Liberatore Mark A. , Miller Kathleen L. , Wolff Carolyn , Cruz Marisa , Lurie Peter , Dal Pan Gerald
Published: March 2018

Background

The opioid epidemic, driven in part by increased prescribing, is a public health emergency. This study examines dispensed prescription patterns and approvals of new opioid analgesic products to investigate whether the introduction of these new drugs increases prescribing.

Methods

Prescribing patterns based on dispensed prescription claims from the U.S. retail setting were assessed with new brand and generic opioid analgesic products approved in the United States from 1997 through 2015.

Results

From 1997 through 2015, the U.S. Food and Drug Administration (Silver Spring, Maryland) approved 263 opioid analgesic products, including 33 brand products. Dispensed prescriptions initially increased 80% from 145 million prescriptions in 1997 to a peak of 260 million prescriptions in 2012 before decreasing by 12% to 228 million prescriptions in 2015. Morphine milligram equivalents dispensed per prescription increased from 486 in 1997 to a peak of 950 in 2010, before decreasing to 905 in 2015. In 2015, generic products accounted for 96% (218/228 million prescriptions) of all opioid analgesic prescriptions dispensed. The remaining prescriptions were dispensed for brand products, of which nearly half were dispensed for one brand product (OxyContin, Purdue, USA).

Conclusions

There has been a dramatic increase in prescriptions dispensed for opioid analgesics since 1997 and an increasing number of opioid analgesic approvals; however, the number of prescriptions dispensed has declined since 2012 despite an increasing number of approvals. Examination of dispensed prescriptions shows a shifting and complex market where multiple factors likely influence prescribing; the approval of new products alone may not be sufficient to be a primary driver of increased prescribing.
Musculoskeletal Multisite Pain and Patterns of Association After Adjusting for Sleep, Physical Activity, and Screen Time in Adolescents
Authors: Silva Anabela G. , Couto Pedro Sá , Queirós Alexandra , Neto Maritza , Rocha Nelson P.
Published: March 2018

Study Design.

Cross-sectional.

Objective.

This study aims to describe how pain at multiple body sites is associated after controlling for other predictive factors such as age, sex, sleeping hours, time spent in physical activity, and time spent in screening based activities in adolescents aged 13 to 19 years.

Summary of Background Data.

The prevalence of multisite pain in adolescents is high, but studies investigating the patterns of association between painful body sites are scarce.

Methods.

Pain for the last 3 months was assessed using Nordic Musculoskeletal Questionnaire. In addition, data on time spent in moderate and vigorous physical activity, sleeping, and in screen based activities were also assessed.

Results.

In univariable analysis of associations, there is a significant association between most painful body sites (odds ratio [OR\ between 1.52 and 3.73, P < 0.05). After controlling for age, sex, physical activity, sleep and screen time, most of the previous associations remain significant (OR between 1.50 and 3.07, P < 0.05).

Conclusion.

This study's results seem to suggest that pain at one body site is more important in determining multiple painful body sites than demographic or lifestyle factors. Longitudinal studies exploring the association and chronology of multisite pain are needed.

Level of Evidence: 3
Private Versus Medicaid Patients Referred to Developmental Behavioral Pediatricians: Do They Differ? A DBPNet Study
Authors: Stein Ruth E. K. , Silver Ellen J. , Augustyn Marilyn C. , Blum Nathan J. , High Pamela , Roizen Nancy J.
Published: March 2018

Background:

It is unknown how insurance status affects elements of evaluation at developmental behavioral (DB) pediatric sites.

Objective:

To compare DB referrals, evaluation, and treatment for children with Medicaid and private insurance.

Design/Methods:

Fifty-six developmental behavioral pediatricians at 12 sites recorded anonymous data on structured forms for ≤15 consecutive referrals. Children with Medicaid (n = 309) and private insurance (n = 393) were compared on sociodemographic factors, referral concerns, evaluation elements, and resulting diagnoses. All significant bivariate findings were verified in multivariable models controlling for site and sociodemographic characteristics.

Results:

Those with Medicaid were significantly less likely to be white (30% vs 63%) and to have parents who went beyond high school (50% vs 92%) and who spoke English (89% vs 97%) (all p < 0.001). Referral sources were similar, except that fewer children with Medicaid were self-referred (12% vs 22%; p < 0.01). Both groups presented with multiple concerns, ∼3/child, especially speech and language delays, autism spectrum disorder, and attention-deficit hyperactivity disorder. Children with Medicaid tended to present more often with concerns about other behavior problems (14% vs 7%; p = 0.05). Wait times to appointments were similar (∼20 weeks), and visits were over 2 hours in length. Only 1 of 92 services and recommendations differed significantly.

Conclusion:

There were few differences in care, but most DB patients presented with multiple concerns and had complex evaluations. Regardless of the insurance type, they experienced long wait times that may be detrimental to therapeutic outcomes.
Risk Factors at Birth Predictive of Subsequent Injury Among Japanese Preschool Children: A Nationwide 5-Year Cohort Study
Authors: Morioka Hisayoshi , Itani Osamu , Jike Maki , Nakagome Sachi , Otsuka Yuichiro , Ohida Takashi
Published: March 2018

Objective:

To identify risk factors at birth that are predictive of subsequent injury among preschool children.

Methods:

Retrospective analysis of population-based birth cohort data from the “Longitudinal Survey of Babies Born in the 21st Century” was performed from 2001 through 2007 in Japan (n = 47,015). The cumulative incidence and the total number of hospitalizations or examinations conducted at medical facilities for injury among children from birth up to the age of 5 years were calculated. To identify risk factors at birth that are predictive of injury, multivariate analysis of data for hospitalization or admission because of injury during a 5-year period (age, 0–5 years) was performed using the total number of hospital examinations as the dependent variable.

Results:

The cumulative incidence (95% confidence interval) of hospital examinations for injury over the 5-year period was 34.8% (34.2%–35.4%) for boys and 27.6% (27.0%–28.2%) for girls. The predictive risk factors at birth we identified for injury among preschool children were sex (boys), heavy birth weight, late birth order, no cohabitation with the grandfather or grandmother, father's long working hours, mother's high education level, and strong intensity of parenting anxiety.

Conclusion:

Based on the results of this study, we identified a number of predictive factors for injury in children. To reduce the risk of injury in the juvenile population as a whole, it is important to pursue a high-risk or population approach by focusing on the predictive factors we have identified.
Management of High-energy Avulsive Ballistic Facial Injury: A Review of the Literature and Algorithmic Approach
Authors: Vaca Elbert E. , Bellamy Justin L. , Sinno Sammy , Rodriguez Eduardo D.
Published: March 2018

Background:

High-energy avulsive ballistic facial injuries pose one of the most significant reconstructive challenges. We conducted a systematic review of the literature to evaluate management trends and outcomes for the treatment of devastating ballistic facial trauma. Furthermore, we describe the senior author’s early and definitive staged reconstructive approach to these challenging patients.

Methods:

A Medline search was conducted to include studies that described timing of treatment, interventions, complications, and/or aesthetic outcomes.

Results:

Initial query revealed 41 articles, of which 17 articles met inclusion criteria. A single comparative study revealed that early versus delayed management resulted in a decreased incidence of soft-tissue contracture, required fewer total procedures, and resulted in shorter hospitalizations (level 3 evidence). Seven of the 9 studies (78%) that advocated delayed reconstruction were from the Middle East, whereas 5 of the 6 studies (83%) advocating immediate or early definitive reconstruction were from the United States. No study compared debridement timing directly in a head-to-head fashion, nor described flap selection based on defect characteristics.

Conclusions:

Existing literature suggests that early and aggressive intervention improves outcomes following avulsive ballistic injuries. Further comparative studies are needed; however, although evidence is limited, the senior author presents a 3-stage reconstructive algorithm advocating early and definitive reconstruction with aesthetic free tissue transfer in an attempt to optimize reconstructive outcomes of these complex injuries.
A NOVEL TECHNIQUE FOR EXTRACTION OF DROPPED BROKEN HAPTICS OF HARD POSTERIOR CHAMBER INTRAOCULAR LENS
Authors: Elwan Mohamed Mamdouh
Published: March 2018

Background/Purpose:

To report a novel technique for extraction of dropped haptics of hard posterior chamber intraocular lens.

Methods:

A 58-year-old woman had undergone cataract extraction, and while implanting the posterior chamber intraocular lens it was dislocated in the anterior vitreous, and the cataract surgeon, tried to remove it by the anterior approach, but he succeeded to remove the optic part only, leaving the haptics dropped, then he referred the case after giving topical and systemic medications to control intraocular inflammation and, the case was prepared for pars plana vitrectomy, then injection of perfluorodecaline to keep the haptics away from the posterior pole then by 23 G vitrectomy probe and, the use of vacuum only, the haptics were removed and the perfluorodecaline was removed.

Results:

After extraction of both haptics by 23 G vitrectomy probe, the case was implanted by a hard polymethylmethacrylate posterior chamber intraocular lens on the sulcus, and postoperatively, the inflammatory signs were subsided and her visual acuity was improved, without any posterior segment complications.

Conclusion:

Dropped haptic of hard posterior chamber intraocular lens can be removed successfully with 23 G vitrectomy probe.
Outcomes of Hemi-Descemet Membrane Endothelial Keratoplasty for Fuchs Endothelial Corneal Dystrophy
Authors: Birbal Rénuka S. , Hsien Shugi , Zygoura Vasiliki , Parker Jack S. , Ham Lisanne , van Dijk Korine , Dapena Isabel , Baydoun Lamis , Melles Gerrit R.J.
Published: March 2018

Purpose:

To report the mid-term outcomes of hemi-Descemet membrane endothelial keratoplasty (hemi-DMEK) performed for Fuchs endothelial corneal dystrophy (FECD).

Methods:

In this prospective, interventional case series, we evaluated clinical outcomes of 10 eyes from 10 patients who underwent hemi-DMEK for FECD. Main outcome measures were best-corrected visual acuity (BCVA), endothelial cell density (ECD), central pachymetry, and postoperative complications.

Results:

At 1 year postoperatively, 7/7 eyes (excluding 2 eyes with low visual potential) reached a BCVA of ≥20/40 (≥0.5), 6/7 (86%) ≥20/25 (≥0.8), 4/7 (57%) ≥20/20 (≥1.0), and 2/7 (29%) 20/17 (≥1.2). BCVA remained stable until 2 years postoperatively (P ≥ 0.05) and further improved thereafter (P < 0.05). Mean ECD decreased from 2740 (±180) cells/mm2 preoperatively to 850 (±300) cells/mm2 (n = 9) at 1 year (P ≤ 0.05) and showed an annual decrease of on average 6% to 7% thereafter (P ≥ 0.05 between consecutive follow-ups). Pachymetry decreased from preoperatively 745 (±153) μm to 533 (±63) μm (n = 9) and 527 (±35) μm (n = 8) at 1 and 3 years postoperatively, respectively. Within the first 6 postoperative months, 4/10 eyes underwent rebubbling for visually significant graft detachment. One eye received secondary circular DMEK for persistent graft detachment 1 month postoperatively; another eye developed secondary graft failure 2.5 years postoperatively, and 1 eye was suspected for an allograft reaction 1.5 years postoperatively.

Conclusions:

Hemi-DMEK may render visual outcomes comparable to those achieved by conventional DMEK. Despite low ECD counts by 6 months, ECD levels remain fairly stable thereafter. Hence, hemi-DMEK may become a potential alternative technique for treatment of FECD while increasing the yield of the endothelial tissue pool.
Location of Disc Hemorrhage and Direction of Progression in Glaucomatous Retinal Nerve Fiber Layer Defects
Authors: Lee Eun Jung , Han Jong Chul , Kee Changwon
Published: March 2018

Purpose:

To investigate the relationship between glaucomatous disc hemorrhage (DH) location with respect to the nasal or temporal margin of the retinal nerve fiber layer defect (RNFLD) and the direction of RNFLD widening.

Materials and Methods:

This is a retrospective, cross-sectional study. Patients with any documented episode of glaucomatous DH throughout the follow-up period, and definite RNFLD widening on retinal nerve fiber layer photographs were analyzed. The location of DH was recorded as either nasal or temporal, and the direction of RNFLD widening was investigated. The laterality of DH location on the RNFLD border and the direction of RNFLD widening were correlated with each other. We also compared clinical parameters between eyes with nasal versus temporal margin DHs.

Results:

We analyzed 123 eyes from 116 patients with definite widening of the RNFLD and glaucomatous DH at the border between the healthy and damaged retinal nerve fiber layer. The most common diagnosis was normal-tension glaucoma (109, 87.9%). The most frequent location of DH was the temporal margin of an inferotemporal RNFLD (75, 61.0%), and the most frequent pattern of change in RNFLD was temporal widening (89, 72.4%). The absolute congruency was 82.9% and the total congruency was 99.2%. No significant differences were identified between eyes with nasal versus temporal margin DHs.

Conclusions:

The lateral location of DH on the RNFLD border was highly congruent with the direction of RNFLD widening. This correspondence of laterality between DH development and progression of RNFLD may suggest an intimate structural relationship during the pathogenesis of DH, at the enlarging RNFLD border.
Temporal dynamics of pain: an application of regime-switching models to ecological momentary assessments in patients with rheumatic diseases
Authors: Schneider Stefan , Junghaenel Doerte U. , Ono Masakatsu , Stone Arthur A.
Published: March 2018

Advances in pain measurement using ecological momentary assessments offer novel opportunities for understanding the temporal dynamics of pain. This study examined whether regime-switching models, which capture processes characterized by recurrent shifts between different states, provide clinically relevant information for characterizing individuals based on their temporal pain patterns. Patients with rheumatic diseases (N = 116) provided 7 to 8 momentary pain ratings per day for 2 weekly periods, separated by 3 months. Regime-switching models extracted measures of Average pain (mean level over time), Amplitude (magnitude of shifts in pain levels), Persistence (average duration of pain states), and Dominance (relative duration of higher vs lower pain states) for each patient and assessment period. After controlling for Average pain, the Persistence of pain states uniquely predicted emotional functioning measures, whereas the Dominance of higher pain uniquely predicted physical functioning and pain interference. Longitudinal analyses of changes over the 3 months largely replicated cross-sectional results. Furthermore, patients' retrospective judgments of their pain were uniquely predicted by Amplitude and Dominance of higher pain states, and global impressions of change over the 3 months were predicted by changes on Dominance, controlling for Average pain levels. The results suggest that regime-switching models can usefully capture temporal dynamics of pain and can contribute to an improved measurement of patients' pain intensity.
Concurrent Acute Myelofibrosis and Acute Lymphoblastic Leukemia in Childhood: Case Report and Review of the Literature
Authors: Friesenbichler Waltraud , Schumich Angela , Simonitsch-Klupp Ingrid , Panzer-Grümayer Renate , Haas Oskar , Mann Georg , Dworzak Michael
Published: March 2018

Myelofibrosis is associated with a wide variety of neoplastic and non-neoplastic bone marrow diseases, predominately myeloproliferative neoplasms and acute myeloid leukemia. The following case documents an unusual patient presenting with pancytopenia and acute myelofibrosis accompanied by precursor B-cell acute lymphoblastic leukemia. This very rare clinical presentation raises questions concerning the relationship between concurrent occurrence of acute myelofibrosis and acute lymphoblastic leukemia.
Efficacy of Extracorporeal Shock Wave Therapy for Lower-Limb Tendinopathy
Authors: Liao Chun-De , Tsauo Jau-Yih , Chen Hung-Chou , Liou Tsan-Hon
Published: March 2018

Objective

Extracorporeal shock wave therapy, including radial shock wave and focused shock wave types, is widely used for managing tendinopathies. The difference in efficacy between the 2 shock wave characteristics with different dosage levels remains controversial, and the purpose of this meta-analysis was to examine it for patients with lower-limb tendinopathy.

Design

A comprehensive search of online databases and search engines was performed. This study included randomized controlled trials reporting the efficacy of extracorporeal shock wave therapy in treating lower-limb tendinopathy. The included randomized controlled trials were subjected to a meta-analysis and risk of bias assessment.

Results

In total, 29 randomized controlled trials were included, all of which had a good methodological quality, with a PEDro score of ≥6/10. General extracorporeal shock wave therapy showed significant effects at the immediate follow-up [pain score: standardized mean difference = −1.41, 95% confidence interval = −2.01 to −0.82, P < 0.00001; function: standardized mean difference = 2.59, 95% confidence interval = 1.54 to 3.64, P < 0.00001] as well as at 3, 6, and ≥12 months. In sequence, high-dosage focused shock wave, high-dosage radial shock wave, and low-dosage radial shock wave had superior pooled effects on overall clinical outcomes.

Conclusions

Extracorporeal shock wave therapy exerted a positive overall effect on pain and function for lower-limb tendinopathy. Shock wave types and dosage levels may have different contributions to treatment efficacy.

To Claim CME Credits

Complete the self-assessment activity and evaluation online at http://www.physiatry.org/JournalCME

CME objectives

Upon completion of this article, the reader should be able to: (1) Describe benefits of extracorporeal shock wave therapy for individuals with lower-limb tendinopathy; (2) Understand the impact of dosing and type of extracorporeal shock wave therapy has on treatment efficacy; and (3) Identify appropriate indications for incorporating extracorporeal shock wave therapy into the treatment plan for patients with lower-limb tendinopathy.

Level

Advanced

Accreditation

The Association of Academic Physiatrists is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Association of Academic Physiatrists designates this Journal-based CME activity for a maximum of 1.0 AMA PRA Category 1 Credit(s)™. Physicians should only claim credit commensurate with the extent of their participation in the activity.
Measuring genetic differentiation from Pool-seq data
Authors: Hivert Valentin , Leblois Raphël , Petit Eric J. , Gautier Mathieu , Vitalis Renaud
Published: March 2018

The recent advent of high throughput sequencing and genotyping technologies enables the comparison of patterns of polymorphisms at a very large number of markers. While the characterization of genetic structure from individual sequencing data remains expensive for many non-model species, it has been shown that sequencing pools of individual DNAs (Pool-seq) represents an attractive and cost-effective alternative. However, analyzing sequence read counts from a DNA pool instead of individual genotypes raises statistical challenges in deriving correct estimates of genetic differentiation. In this article, we provide a method-of-moments estimator ofFSTfor Pool-seq data, based on an analysis-of-variance framework. We show, by means of simulations, that this new estimator is unbiased, and outperforms previously proposed estimators. We evaluate the robustness of our estimator to model misspecification, such as sequencing errors and uneven contributions of individual DNAs to the pools. Last, by reanalyzing published Pool-seq data of different ecotypes of the prickly sculpinCottus asper, we show how the use of an unbiasedFSTestimator may question the interpretation of population structure inferred from previous analyses.
Mechanisms for European BatLyssavirussubtype 1 persistence in non-synanthropic bats: insights from a modeling study
Authors: Colombi Davide , Serra-Cobo Jordi , Métras Raphaëlle , Apolloni Andrea , Poletto Chiara , López-Roig Marc , Bourhy Hervé , Colizza Vittoria
Published: March 2018

Background

Lyssaviruses are pathogens of bat origin of considerable zoonotic concern being the causative agent for rabies disease, however our understanding of their persistence in bat populations remains very scarce.

Methods

Leveraging existing data from an extensive ecological field survey characterizingMyotis myotisandMiniopterus schreibersiibat species in the Catalonia region, we develop a data-driven spatially explicit metapopulation model to identify the mechanisms of the empirically observed persistence of European Bat Lyssavirus subtype 1 (EBLV-1), the most common lyssavirus species found in Europe. We consider different disease progressions accounting for lethal infection, immunity waning, and potential cross-species transmission when the two populations share the same refuge along the migratory path ofM. schreibersii.

Results

We find that EBLV-1 persistence relies on host spatial structure through the migratory nature ofM. schreibersiibats, on cross-species mixing withM. myotispopulation, and on a disease progression leading to survival of infected animals followed by temporary immunity. The higher fragmentation along the northern portion of the migratory path is necessary to maintain EBLV-1 sustained circulation in both species, whereas persistence would not be ensured in the single colony ofM. myotis.Our study provides first estimates for the EBLV-1 transmission potential inM. schreibersiibats and average duration of immunity in the host species, yielding values compatible with previous empirical observations inM. myotisbats.

Conclusions

Habitats sharing and the strong spatial component of EBLV-1 transmission dynamics identified as key drivers in this ecological context may help understanding the observed spatial diffusion of the virus at a larger scale and across a diverse range of host species, through long-range migration and seeding of local populations. Our approach can be readily adapted to other zoonotic pathogens of public health concern.
Novel susceptibility loci and genetic regulation mechanisms for type 2 diabetes
Authors: Xue Angli , Wu Yang , Zhu Zhihong , Zhang Futao , Kemper Kathryn E , Zheng Zhili , Yengo Loic , Lloyd-Jones Luke R. , Sidorenko Julia , Wu Yeda ,   eQTLGen Consortium, McRae Allan F , Visscher Peter M , Zeng Jian , Yang Jian
Published: March 2018

We conducted a meta-analysis of genome-wide association studies (GWAS) with ∼16 million genotyped/imputed genetic variants in 62,892 type 2 diabetes (T2D) cases and 596,424 controls of European ancestry. We identified 139 common and 4 rare (minor allele frequency < 0.01) variants associated with T2D, 42 of which (39 common and 3 rare variants) were independent of the known variants. Integration of the gene expression data from blood (n = 14,115 and 2,765) and other T2D-relevant tissues (n = up to 385) with the GWAS results identified 33 putative functional genes for T2D, three of which were targeted by approved drugs. A further integration of DNA methylation (n = 1,980) and epigenomic annotations data highlighted three putative T2D genes (CAMK1D, TP53INP1 and ATP5G1) with plausible regulatory mechanisms whereby a genetic variant exerts an effect on T2D through epigenetic regulation of gene expression. We further found evidence that the T2D-associated loci have been under purifying selection.
Proximity-dependent proteomics of theChlamydia trachomatisinclusion membrane reveals functional interactions with endoplasmic reticulum exit sites
Authors: Dickinson Mary S. , Anderson Lindsey N. , Webb-Robertson Bobbie-Jo M. , Hansen Joshua R. , Smith Richard D. , Wright Aaron T. , Hybiske Kevin
Published: March 2018

Chlamydia trachomatisis the most common bacterial sexually transmitted infection, responsible for millions of infections each year. Despite this high prevalence, the elucidation of the molecular mechanisms ofChlamydiapathogenesis has been difficult due to limitations in genetic tools and its intracellular developmental cycle. Within a host epithelial cell, chlamydiae replicate within a vacuole called the inclusion. ManyChlamydia–host interactions are thought to be mediated by the Inc family of type III secreted proteins that are anchored in the inclusion membrane, but their array of host targets are largely unknown. To investigate how the inclusion membrane proteome changes over the course of an infected cell, we have adapted the APEX system of proximity-dependent biotinylation. APEX is capable of specifically labeling proteins within a 20 nm radius in living cells. We transformedC. trachomatisto express the enzyme APEX fused to known inclusion membrane proteins, allowing biotinylation and pull-down of inclusion-associated proteins. Using quantitative mass spectrometry against APEX labeled samples, we identified over 400 proteins associated with the inclusion membrane at early, middle, and late stages of epithelial cell infection. This system was sensitive enough to detect inclusion interacting proteins early in the developmental cycle, at 8 hours post infection, a previously intractable time point. Mass spectrometry analysis revealed a novel, early association betweenC. trachomatisinclusions and endoplasmic reticulum exit sites (ERES), functional regions of the ER where COPII-coated vesicles originate. Pharmacological and genetic disruption of ERES function severely restricted early chlamydial growth and the development of infectious progeny. APEX is therefore a powerful in situ approach for identifying critical protein interactions on the membranes of pathogen-containing vacuoles. Furthermore, the data derived from proteomic mapping ofChlamydiainclusions has illuminated an important functional role for ERES in promoting chlamydial developmental growth.
Structural transition and antibody binding of Ebola GP and Zika E proteins from pre-fusion to fusion-initiation states
Authors: Lappala-Vernon A , Nishima W , Miner J C , Fenimore P W , Fischer W , Hraber P T , Zhang M , McMahon B H , Tung C-S
Published: March 2018

Membrane fusion proteins are responsible for viral entry into host cells– a crucial first step in viral infection. These proteins undergo large conformational changes from pre-fusion to fusion initiation structures, and, despite differences in viral genomes and disease etiology, many fusion proteins are arranged as trimers. Structural information for both pre-fusion and fusion initiation states is critical for understanding virus neutralization by the host immune system. In the case of Ebola glycoprotein (GP) and Zika envelope protein (Zika E), pre-fusion state structures have been identified experimentally, but only partial structures of fusion initiation states have been described. While the fusion initiation structure is in an energetically unfavorable state that is difficult to solve experimentally, the existing structural information combined with computational approaches enabled the modeling of fusion initiation state structures of both proteins. These structural models provide an improved understanding of four different neutralizing antibodies in the prevention of viral host entry.
Eco-evolutionary community turnover following environmental change
Authors: Lasky Jesse R.
Published: March 2018

Co-occurring species often differ in intraspecific genetic diversity, which in turn can affect adaptation in response to environmental change. Specifically, the simultaneous evolutionary responses of co-occurring species to temporal environmental change may influence community dynamics. Local adaptation along environmental gradients combined with gene flow can promote genetic diversity of traits under selection within populations. Here I build off existing quantitative genetic theory to study community dynamics of locally adapted species in response to temporal environmental change. I show that species with greater gene flow have lower equilibrium population size due to maladaptive immigrant genotypes (migration load). However, following abrupt environmental change that leaves all species initially maladapted, high gene flow species adapt faster due to greater standing genetic diversity. As a result, communities may undergo a transient reversal in relative abundance, sometimes only after substantial lag periods. If constant temporal environmental change is applied, the community exhibits a shift toward stable dominance by species with intermediate gene flow. High gene flow species can sometimes increase abundance under environmental change if environmental change supresses superior competitor but lower gene flow species. The community dynamics observed here parallel the purely ecological successional dynamics following disturbances and are analogous to the transient benefit of hypermutator alleles under changing environments. My results demonstrate how interspecific variation in life history can have far-reaching impacts on eco-evolutionary community response to environmental change.
Social intelligence model with multiple internal models
Authors: Isomura Takuya , Parr Thomas , Friston Karl
Published: March 2018

To exhibit social intelligence, animals have to recognize who they are communicating with. One way to make this inference is to select among multiple internal generative models of each conspecific. This induces an interesting problem: when receiving sensory input generated by a particular conspecific, how does an animal know which internal model to update? We consider a theoretical and neurobiologically plausible solution that enables inference and learning under multiple generative models by integrating active inference and (online) Bayesian model selection. This scheme fits sensory inputs under each generative model. Model parameters are then updated in proportion to the probability it could have generated the current input (i.e., model evidence). We show that a synthetic bird who employs the proposed scheme successfully learns and distinguishes (real zebra finch) birdsongs generated by several different birds. These results highlight the utility of having multiple internal models to make inferences in complicated social environments.
Lipid perturbation-activated IRE-1 modulates autophagy and lipolysis during endoplasmic reticulum stress
Authors: Koh Jhee Hong , Wang Lei , Beaudoin-Chabot Caroline , Thibault Guillaume
Published: March 2018

Metabolic disorders such as obesity and nonalcoholic fatty liver disease (NAFLD) are emerging diseases that affect the global population. One facet of these disorders is attributed to the disturbance of membrane lipid composition. Perturbation of endoplasmic reticulum (ER) homeostasis through changes in membrane phospholipid composition results in activation of the unfolded protein response (UPR) and causes dramatic translational and transcriptional changes in the cell. To restore cellular homeostasis, the three highly conserved UPR transducers ATF6, IRE1, and PERK mediate cellular processes upon ER stress. The role of the UPR in proteotoxic stress caused by the accumulation of misfolded proteins is well understood but much less so under lipid perturbation-induced UPR (UPRLP). We found that genetically disrupted phosphatidylcholine synthesis inC. eleganscauses, lipid perturbation, lipid droplet accumulation, and induced ER stress, all hallmarks of NAFLD. Transcriptional profiling of UPRLPanimals shows a unique subset of genes modulated in an UPR-dependent manner that is unaffected by proteotoxic stress (UPRPT). Among these, we identified autophagy genesbec-1andlgg-1and the lipid droplet-associated lipaseatgl-1to be modulated by IRE-1. Considering the important role of lipid homeostasis and how its impairment contributes to the pathology of metabolic diseases, our data uncovers the indispensable role of a fully functional UPR program in regulating lipid homeostasis in the face of chronic ER stress and lipotoxicity.
Open-pFind enables precise, comprehensive and rapid peptide identification in shotgun proteomics
Authors: Chi Hao , Liu Chao , Yang Hao , Zeng Wen-Feng , Wu Long , Zhou Wen-Jing , Niu Xiu-Nan , Ding Yue-He , Zhang Yao , Wang Rui-Min , Wang Zhao-Wei , Chen Zhen-Lin , Sun Rui-Xiang , Liu Tao , Tan Guang-Ming , Dong Meng-Qiu , Xu Ping , Zhang Pei-Heng , He Si-Min
Published: March 2018

Shotgun proteomics has grown rapidly in recent decades, but a large fraction of tandem mass spectrometry (MS/MS) data in shotgun proteomics are not successfully identified. We have developed a novel database search algorithm, Open-pFind, to efficiently identify peptides even in an ultra-large search space which takes into account unexpected modifications, amino acid mutations, semi- or non-specific digestion and co-eluting peptides. Tested on two metabolically labeled MS/MS datasets, Open-pFind reported 50.5‒117.0% more peptide-spectrum matches (PSMs) than the seven other advanced algorithms. More importantly, the Open-pFind results were more credible judged by the verification experiments using stable isotopic labeling. Tested on four additional large-scale datasets, 70‒85% of the spectra were confidently identified, and high-quality spectra were nearly completely interpreted by Open-pFind. Further, Open-pFind was over 40 times faster than the other three open search algorithms and 2‒3 times faster than three restricted search algorithms. Re-analysis of an entire human proteome dataset consisting of ∼25 million spectra using Open-pFind identified a total of 14,064 proteins encoded by 12,723 genes by requiring at least two uniquely identified peptides. In this search results, Open-pFind also excelled in an independent test for false positives based on the presence or absence of olfactory receptors. Thus, a practical use of the open search strategy has been realized by Open-pFind for the truly global-scale proteomics experiments of today and in the future.
Prestimulus neural alpha power predicts confidence in discriminating identical tones
Authors: Wöstmann Malte , Waschke Leonhard , Obleser Jonas
Published: March 2018

There is growing evidence that the power of prestimulus neural alpha oscillations (∼10 Hz) holds information on a perceiver’s bias or confidence in an ensuing perceptual decision, rather than perceptual sensitivity per se. Obviously, however, confidence also depends on the physical evidence available in the stimulus as well as on task performance. If prestimulus alpha power has a direct impact on decision confidence, this link should hold independent of variations in stimulus evidence and performance. We tested this assertion in a paradigm where human listeners (n = 17) rated their confidence in the discrimination of the pitch of two identical tones. Lower prestimulus alpha power in the electroencephalogram (EEG) was predictive of higher confidence ratings, but not of the decision outcome (i.e., judging the first or the second tone as being higher in pitch). Importantly, the link between prestimulus alpha power and decision confidence was not mediated by auditory evoked activity. Our findings demonstrate that the link between prestimulus alpha power and decision confidence does not hinge on physical evidence in the stimulus or task performance. Instead, these results speak to a model wherein low prestimulus alpha power increases neural baseline excitability, which is reflected in enhanced stimulus-evoked neural responses and higher confidence.

Significance statement

In order to understand the mechanistic relevance of neural oscillations for perception, we here relate these directly to changes in human auditory decision confidence. Human subjects rated their confidence in the discrimination of the pitch of two tones, which were, unbeknownst to the listener, physically identical. In the absence of changing evidence in the physical stimulus or changes in task performance, we demonstrate that prestimulus alpha power negatively relates to decision confidence. Our results support a model of cortical alpha oscillations as a proxy for neural baseline excitability in which lower prestimulus alpha power does not lead to more precise but rather to overall amplified neural representations.
Identifying the genetic basis of variation in cell behaviour in human iPS cell lines from healthy donors
Authors: Vigilante Alessandra , Laddach Anna , Moens Nathalie , Meleckyte Ruta , Leha Andreas , Ghahramani Arsham , Culley Oliver J. , Kathuria Annie , Hurling Chloe , Vickers Alice , Tewary Mukul , Zandstra Peter ,   HipSci Consortium, Durbin Richard , Fraternali Franca , Stegle Oliver , Birney Ewan , Luscombe Nicholas M. , Danovi Davide , Watt Fiona M.
Published: March 2018

Large cohorts of human iPSCs from healthy donors are potentially a powerful tool for investigating the relationship between genetic variants and cellular phenotypes. Here we integrate high content imaging, gene expression and DNA sequence datasets for over 100 human iPSC lines to identify the genetic basis of inter-individual variability in cell behaviour. By applying a dimensionality reduction approach, Probabilistic Estimation of Expression Residuals (PEER), we identified genes that correlated in expression with intrinsic (genetic) and extrinsic (ECM) factors. However, variation in mRNA levels could not account for outlier cell behaviour. Instead, we identified rare, deleterious SNVs in the coding sequence of genes involved in ECM adhesion that occurred in cell lines that were outliers for one or more phenotypes such as cell spreading. These also correlated with altered germ layer differentiation on micropatterned surfaces. Our study thus establishes a strategy for integrating genetic and cell biological measurements for high-throughput analysis.
Hierarchy, Morphology, and Adaptive Radiation: a Test of Osborn’s Law in the Carnivora
Authors: Slater Graham J. , Friscia Anthony R.
Published: March 2018

Abstract

Henry Fairfield Osborn’s law of adaptive radiation was intended to explain the early proliferation of morphological and functional variation in diversifying clades. Yet, despite much theoretical development and empirical testing, questions remain regarding the taxonomic levels at which adaptive radiation occurs, the traits involved, and its frequency across the tree of life. Here, we evaluate support for this “early burst” model of adaptive radiation in 14 ecomorphological traits plus body mass for the extant mammalian order Carnivora. Strong support for an early burst adaptive radiation is recovered for molar grinding area, a key proxy for diet. However, we find no evidence for early burst–like dynamics in body mass or multivariate trait data, suggesting a decoupling of evolutionary modes among traits driven by dietary specialization. Furthermore, the signal of an early burst is only recovered for Carnivora, and not in family–level clades. The lack of support for the early burst model of morphological adaptive radiation in previous phylogenetic studies may be a consequence of focusing on the wrong traits at the wrong taxonomic levels. Osborn’s law predicted that adaptive radiation should be hierarchically structured, and the search for its signature and understanding of its prevalence will require a renewed focus on functional traits and their evolution over higher-level clades.