bluuebunny/crossref_metadata_2025 huggingface dataset:
Transplantation Blues: Inadvertent Staining of Amyloid Deposits With Trypan Blue
Authors: Marcon Agathe , Périllat Nicolas , Garcin Thibaud , Jullienne Rémy , He Zhiguo , Forest Fabien , Gauthier Anne Sophie , Gain Philippe , Thuret Gilles
Published: March 2018

Purpose:

To describe inadvertent persistent staining of stromal amyloid deposits by trypan blue (TB) after penetrating keratoplasty (PK) and Descemet membrane endothelial keratoplasty (DMEK) performed in patients with corneal amyloidosis.

Methods:

Case series of patients with corneal amyloidosis in whom intraoperative TB was used.

Results:

One patient, hospitalized for acute rejection 6 weeks after DMEK, presented with an intense blue staining of small, spindle-shaped structures in the anterior half of the cornea. DMEK had been performed for endothelial failure of a previous PK procedure done 13 years earlier for advanced lattice corneal dystrophy (LCD). After 6 months, the stromal blue tattoo persisted with impaired visual acuity, and PK was performed. Blue-stained structures were amyloid deposits characteristic of LCD recurrence. In parallel, among 85 consecutive triple procedures (PK + cataract + intraocular lens [IOL]) performed over 7 years, in which TB was used, only patients with LCD (n = 18 eyes in 17 patients) or presumed secondary amyloidosis due to chronic inflammation (n = 1), presented an isolated intense blue ring of the graft–host interface. This persisted up to 7 years with no clinical consequence.

Conclusions:

TB can stain corneal amyloid deposits. After PK, staining is limited to the recipient peripheral cornea and has no apparent clinical consequence. However, during DMEK performed after a failed PK, TB stains fibrils accumulated during slow LCD recurrence and scattered on the whole graft. The long-term staining duration indicates strong interactions between TB and amyloid.
Histopathology of Exfoliation Syndrome
Authors: Kivelä Tero T.
Published: March 2018

Exfoliation syndrome (XFS) is characterized by light and electron microscopy by age-dependent gradual accumulation of whitish material of largely unknown composition and origin along both the anterior and posterior chambers and widely within the iris stroma. These deposits can be fairly specifically labeled with selected antibodies and lectins. Immunohistochemistry shows that intraocular exfoliation deposits share antigens with the microfibrillar elastic fiber system and several basement membrane components, including carbohydrate epitopes on glycosaminoglycans, proteoglycans, and cell adhesion molecules. The earliest histopathologic manifestation of XFS seems to be the deposition of characteristic fibers in various extraocular and anterior segment tissues, as observed by electron microscopy, and perivascular deposition of material within the iris stroma, which is antigenically typical of that found in classic intraocular exfoliation deposits. These findings precede the clinical diagnosis of XFS and likewise can be detected in the seemingly uninvolved fellow eyes of patients with clinically unilateral XFS. Indeed, histopathologic examination of capsulotomy, iridectomy, and trabeculectomy specimens can lead to a clinically unexpected diagnosis of XFS. Exfoliation fibers are additionally found widely distributed in extraocular connective tissues and visceral organs, but the matrix of these fibers seems to differ from that of intraocular deposits. In addition to this histopathologic discrepancy, both the frequent occurrence of clinically unilateral, histopathologically highly asymmetric exfoliation deposits, and the relationship between the early iris vasculopathy that not infrequently may be observed histopathologically for years before classic widespread exfoliation deposits appear along the anterior and posterior chambers remain to be resolved.
Clackamas County Public Health: Employee Engagement in Quality Improvement and Performance Management Activities
Authors: Mason Philip
Published: March 2018

This case report provides an example of a local health department's use of performance management tools across its agency. An emphasis is on engaging staff across all levels of the organization so that employees can understand how their work affects overall performance management.
State Health Agencies' Perceptions of the Benefits of Accreditation
Authors: Kittle Alannah , Liss-Levinson Rivka
Published: March 2018

The national voluntary accreditation program serves to encourage health agencies to seek departmental accreditation as a mechanism for continuous quality improvement. This study utilizes data from the 2016 Association of State and Territorial Health Officials Profile Survey to examine the perceived benefits of accreditation among state health agencies. Respondents answered questions on topics such as agency structure, workforce, and quality improvement activities. Frequencies and cross tabulations were conducted using IBM SPSS (version 21) statistical software. Results indicate that among accredited agencies, the most commonly endorsed benefits of accreditation include stimulating quality and performance improvement opportunities (95%), strengthening the culture of quality improvement (90%), and stimulating greater collaboration across departments/units within the agency (90%). Policy and practice implications, such as how these data can be used to promote accreditation within health agencies, as well as how accreditation strengthens governmental public health systems, are also discussed.
Accreditation's Role in Bolstering Resilience in the Face of the Zika Virus Outbreak
Authors: Philip Celeste , Wells Kelli T. , Eggert Russell , Elmore Jennifer , Jean Reynald , Johnson Jennifer , Lane Jeanne , Lopez Ximena , Rivera Lillian , Samir Elmir , Strokin Natasha , Villalta Yesenia , Ynestroza Rene
Published: March 2018

The Florida Department of Health (Department) received accreditation status as an integrated public health system from the Public Health Accreditation Board (PHAB) in 2 phases: the State Health Office received accreditation in June 2014 and the 67 county health departments received accreditation in March 2016. Six weeks after PHAB awarded accreditation to the Department as an integrated public health system in March 2016, the World Health Organization declared the Zika outbreak in the Americas a Public Health Emergency of International Concern. Even in that short time, integrated public health accreditation, along with the other components of the Department's performance management system, allowed the Department to address this public health emergency, especially in Miami-Dade County, where the impact of Zika was significant. This case report describes the local response in Miami-Dade County and supporting statewide efforts. Public health departments should consider how public health accreditation could strengthen their ability to fulfill their public health mission. This article provides rationale for state and local health departments to seek accreditation.
Using Quality Improvement to Improve Internal and External Coordination and Referrals
Authors: Cain Katherine L. , Collins Ragan P.
Published: March 2018

As part of accreditation, Public Health Accreditation Board site visitors recommended that the New Orleans Health Department strengthen its quality improvement program. With support from the Public Health Accreditation Board, the New Orleans Health Department subsequently embarked on a data-driven planning process through which it prioritized quality improvement projects for 2016. One of these projects aimed to improve referrals to New Orleans Health Department's direct services programs from local clinics and hospitals to better provide our most vulnerable residents with a continuum of care. After completing a cause-and-effect analysis, we implemented a solution involving increased outreach to health care institutions and saw annual participation increase in 3 out of 4 of our programs. We leveraged this work to successfully apply for funding to create a centralized referral system, which will facilitate partnerships among local health and human service agencies and improve access to services. This is one example of how accreditation has benefited our health department and our community. We have found that the accreditation process promotes a culture of quality and helps health departments identify and address areas for improvement.
Changes in Local Public Health System Performance Before and After Attainment of National Accreditation Standards
Authors: Ingram Richard C. , Mays Glen P. , Kussainov Nurlan
Published: March 2018

Objective:

The aim of this study is to investigate the impact of Public Health Accreditation Board (PHAB) accreditation on the delivery of public health services and on participation from other sectors in the delivery of public health services in local public health systems.

Design:

This study uses a longitudinal repeated measures design to identify differences between a cohort of public health systems containing PHAB-accredited local health departments and a cohort of public health systems containing unaccredited local health departments. It uses data spanning from 2006 to 2016.

Setting:

This study examines a cohort of local public health systems that serves large populations and contains unaccredited and PHAB-accredited local health departments.

Participants:

Data in this study were collected from the directors of health departments that include local public health systems followed in the National Longitudinal Study of Public Health Systems.

Intervention:

The intervention examined is PHAB accreditation.

Main Outcome Measures:

The study focuses on 4 areas: the delivery of core public health services, local health department contribution toward these services, participation in the delivery of these services by other members of the public health system, and public health system makeup.

Results:

Prior to the advent of accreditation, public health systems containing local health departments that were later accredited by PHAB appear quite similar to their unaccredited peers. Substantial differences between the 2 cohorts appear to manifest themselves after the advent of accreditation. Specifically, the accredited cohort seems to offer a broader array of public health services, involve more partners in the delivery of those services, and enjoy a higher percentage of comprehensive public health systems.

Conclusions:

The results of this study suggest that accreditation may yield significant benefits and may help public health systems develop the public health system capital necessary to protect and promote the public's health.
A Menu to Evaluate Factors Influencing Implementation of Obesity Prevention Early Care and Education Regulations
Authors: Sawicki Erin , Barker Dianne C. , Gutman Marjorie A. , Caughlan Ian , Yochelson Marissa , Grob George
Published: March 2018

Context:

In recent years, several states have adopted new regulations concerning nutrition, physical activity, and screen time in early care and education (ECE) settings to help prevent childhood obesity.

Objective:

To disseminate a menu of factors that facilitate and/or impede implementation of obesity prevention regulations in ECE settings.

Design:

To create the menu, we condensed and categorized factors identified in the literature and through field work by placing them within domains. We applied the menu by conducting semistructured interviews during a pilot test assessing implementation of ECE regulations in Colorado.

Setting and Participants:

We first interviewed state and local government agency leaders responsible for policy oversight, and state employees and contractors who acted as intermediaries to direct implementers. We then interviewed directors at ECE centers in the Denver, Colorado, area. We selected 21 ECE centers for a site visit on the basis of feasibility, percentage of low-income families, and diversity in race and ethnicity at each center. Seven centers participated.

Main Outcome Measures:

Minor and major facilitators and impediments to implementation of childhood obesity prevention regulations in ECE settings.

Results:

The resulting menu includes 7 domains and 39 factors influential for implementation of ECE regulations. Of these 39 factors, interviewees identified 7 facilitating factors (4 major and 3 minor) and 2 impeding factors (both major). Major facilitating factors were buy-in from parents/caregivers, training and communication provided by governing authority and their contractors, and low level of change required by the regulations themselves. Major impeding factors were timing of implementation and balancing the demands of the regulations against other priorities.

Conclusions:

The menu developed by our research team, combined with existing frameworks in dissemination and implementation research, can be used by researchers, practitioners, and policy makers to anticipate factors that facilitate and/or impede implementation of ECE policies to prevent childhood obesity.
Quantification of Total and Intracellular Sodium Concentration in Primary Prostate Cancer and Adjacent Normal Prostate Tissue With Magnetic Resonance Imaging
Authors: Barrett Tristan , Riemer Frank , McLean Mary A. , Kaggie Josh , Robb Fraser , Tropp James S. , Warren Anne , Bratt Ola , Shah Nimish , Gnanapragasam Vincent J. , Gilbert Fiona J. , Graves Martin J. , Gallagher Ferdia A.
Published: March 2018

Objectives

The aim of this study was to measure the tissue sodium concentration (TSC) within tumors and normal prostate in prostate cancer patients, using prostatectomy as pathological criterion standard.

Materials and Methods

Fifteen patients with biopsy-proven, magnetic resonance imaging (MRI) visible, intermediate- or high-risk prostate cancer underwent a dedicated research sodium MRI, before treatment with radical prostatectomy. All participants signed written informed consent for this institutional review board–approved prospective study. 3 T MRI acquired using a dedicated multinuclear clamshell transmit coil and a bespoke dual-tuned 1H/23Na endorectal receive coil, with intracellular-sodium imaging acquired using inversion recovery sequences; a phantom-based calibration enabled quantitative sodium maps. Regions of interest were defined for normal peripheral zone (PZ) and transition zone (TZ) and tumor regions, referenced from histopathology maps. A 1-way analysis of variance compared normal and tumor tissue, using Tukey test for multiple comparisons.

Results

Two patients were excluded due to artifact; software error resulted in 1 further intracellular-sodium failure. Fifteen tumors were detected (13 PZ, 2 TZ) in 13 patients: Gleason 3 + 3 (n = 1), 3 + 4 (6), 3 + 5 (2), 4 + 3 (5), 4 + 5 (1). Both mean TSC and intracellular-sodium were significantly higher in normal PZ (39.2 and 17.5 mmol/L, respectively) versus normal TZ (32.9 and 14.7; P < 0.001 and P = 0.02). Mean TSC in PZ tumor (45.0 mmol/L) was significantly higher than both normal PZ and TZ tissue (P < 0.001). Intracellular sodium in PZ tumors (19.9 mmol/L) was significantly higher than normal TZ (P < 0.001) but not normal PZ (P = 0.05). Mean TSC and intracellular-sodium was lower in Gleason ≤3 + 4 tumors (44.4 and 19.5 mmol/L, respectively) versus ≥4 + 3 (45.6 and 20.2), but this was not significant (P = 0.19 and P = 0.29).

Conclusions

Tissue sodium concentration and intracellular sodium concentrations of prostate tumors were quantified, with PZ tumors demonstrating a significantly increased TSC.
Effect of hypobaria and hyperoxia during sepsis on survival and energy metabolism
Authors: Choi Myeongjin , Tamrakar Pratistha , Schuck Patricia F. , Proctor Julie L. , Moore Ashley , Asbury Katrina , Fiskum Gary , Coksaygan Turhan , Cross Alan S.
Published: March 2018

BACKGROUND

Injured warfighters air evacuated to tertiary medical care facilities are subjected to many stresses that may promote the development of sepsis. In this study, we tested the hypothesis that exposure to “in-flight” hypobaria and/or hyperoxia within 24 hours after onset of intra-abdominal infection in rats accelerates the development and/or severity of sepsis and neurologic injury in survivors.

METHODS

Sprague-Dawley rats underwent cecal ligation/puncture (CLP) or sham procedures. Twenty-four hours later, rats were then placed in hypobaric chambers for 6 hours and assigned to normobaric conditions and maintained at either 21% or 100% O2, or under hypobaric conditions (pressure equivalent to an altitude of 8,000 ft) but maintained under either 28% or 100% O2. Two days after CLP or sham, blood samples were obtained for cytokine levels, and mitochondria were isolated from the brain and heart of a subset of animals for analysis of mitochondrial oxygen consumption. Animals were also evaluated for neuromotor impairment before and 15 days postsurgery.

RESULTS

Among the 70 rats studied, 16.7% of CLP but none of the sham-treated rats died. All of the CLP but none of the sham rats had evidence of peritonitis at 2 days. Twenty percent (6 of 30) CLP rats undergoing hypobaria versus 12.5% (3 of 24) of CLP rats exposed to normobaria died (p = 0.715) while 12% (3 of 25) of CLP rats exposed to hyperoxia versus 20.7% (6 of 29) of CLP rats exposed to normoxia died (p = 0.48). The ratio of mitochondrial ATP-generating O2 consumption to resting respiration was higher in the CLP plus hypobaria under 100% compared with shams. The only difference in H2O2 production was observed in mitochondria from CLP rats exposed to hyperoxia under normobaric conditions. Composite neurologic scores obtained 15 days postinjury were lower than those at baseline for shams.

CONCLUSION

We conclude that neither “in-flight” hyperoxia nor hypobaria exacerbate sepsis or neurologic injury.
Modulation of naturalistic maladaptive memories using behavioural and pharmacological reconsolidation-interfering strategies: A systematic review and meta-analysis of clinical and 'sub-clinical' studies
Authors: Walsh Katie H , Das Ravi K , Saladin Michael E , Kamboj Sunjeev K
Published: March 2018

Consolidated memories can undergo enduring modification through retrieval-dependent treatments that modulate reconsolidation. This has been suggested to represent a potentially transformative clinical strategy for weakening or overwriting the maladaptive memories that underlie substance use and anxiety/trauma-related disorders. However, the ability to modulate naturalistic maladaptive memories may be limited by boundary conditions imposed on reconsolidation by the nature of these memories. As such, the true potential of reconsolidation therapy is currently unknown. Here, we report a meta-analyses of behavioural and pharmacological studies examining retrieval-dependent modulation of reward and threat memories in (sub)clinical substance use and anxiety/trauma respectively. Of 4936 publications assessed for eligibility, 7 studies of substance use, and 9 of anxiety (phobia) and trauma-related symptoms were included in the meta-analyses. Overall, the findings were in the predicted direction, with the majority of effect sizes favouring the Retrieval + Treatment condition. However, the magnitude of effects depended upon the nature of the treatment type, with pharmacological interventions (relative to behavioural strategies) showing a clearer beneficial effect in studies of phobia/trauma and post-retrieval behavioural strategies, a (significantly) larger effect in substance use studies. However, high levels of heterogeneity and small sample sizes limit the strength of conclusions that can be drawn at this stage of inquiry. We hope this review will provide an impetus to address these issues in future research.
The ultra-sensitive Nodewalk technique identifies stochastic from virtual, population-based enhancer hubs regulatingMYCin 3D: Implications for the fitness of cancer cells
Authors: Sumida Noriyuki , Sifakis Emmanouil G , Scholz Barbara A , Fernandez-Woodbridge Alejandro , Kiani Narsis A , Gomez-Cabrero David , Svensson J Peter , Tegner Jesper , Göndör Anita , Ohlsson Rolf
Published: March 2018

The relationship between stochastic transcriptional bursts and dynamic 3D chromatin states is not well understood due to poor sensitivity and/or resolution of current chromatin structure-based assays. Consequently, it is not well established if enhancers operate individually and/or in clusters to coordinate gene transcription. In the current study, we introduce Nodewalk, which uniquely combines high sensitivity with high resolution to enable the analysis of chromatin networks in minute input material. The >10,000-fold increase in sensitivity over other many-to-all competing methods uncovered that active chromatin hubs identified in large input material, corresponding to 10 000 cells, flanking theMYClocus are primarily virtual. Thus, the close agreement between chromatin interactomes generated from aliquots corresponding to less than 10 cells with randomly re-sampled interactomes, we find that numerous distal enhancers positioned within flanking topologically associating domains (TADs) converge onMYCin largely mutually exclusive manners. Moreover, when comparing with several enhancer baits, the assignment of theMYClocus as the node with the highest dynamic importance index, indicates that it isMYCtargeting its enhancers, rather thanvice versa.Dynamic changes in the configuration of the boundary between TADs flankingMYCunderlie numerous stochastic encounters with a diverse set of enhancers to depict the plasticity of its transcriptional regulation. Such an arrangement might increase the fitness of the cancer cell by increasing the probability ofMYCtranscription in response to a wide range of environmental cues encountered by the cell during the neoplastic process.
Bradyrhizobium diazoefficiens USDA 110-Glycine max interactome provides candidate proteins associated with symbiosis
Authors: Zhang Li , Liu Jin-Yang , Gu Huan , Du Yanfang , Zuo Jian-Fang , Zhang Zhibin , Zhang Menglin , Li Pan , Dunwell Jim M. , Cao Yangrong , Zhang Zuxin , Zhang Yuan-Ming
Published: March 2018

Although the legume-rhizobium symbiosis is a most important biological process, there is a limited knowledge about the protein interaction network between host and symbiont. Using interolog and domain-based approaches, we constructed an inter-species protein interactome with 5115 protein-protein interactions between 2291 Glycine max and 290 Bradyrhizobium diazoefficiens USDA 110 proteins. The interactome was validated by expression pattern analysis in nodules, GO term semantic similarity, and co-expression analysis. One sub-network was further confirmed using luciferase complementation image assay. In the G. max-B. diazoefficiens interactome, bacterial proteins are mainly ion channel and transporters of carbohydrates and cations, while G. max proteins are mainly involved in the processes of metabolism, signal transduction, and transport. We also identified the top ten highly interacting proteins (hubs) for each of the two species. KEGG pathway analysis for each hub showed that two 14-3-3 proteins (SGF14g and SGF14k) and five heat shock proteins in G. max are possibly involved in symbiosis, and ten hubs in B. diazoefficiens may be important symbiotic effectors. Subnetwork analysis showed that 18 symbiosis-related SNARE proteins may play roles in regulating bacterial ion channels, and SGF14g and SGF14k possibly regulate the rhizobium dicarboxylate transport protein DctA. The predicted interactome and symbiosis proteins provide a valuable basis for understanding the molecular mechanism of root nodule symbiosis in soybean.
G2P: Using machine learning to understand and predict genes causing rare neurological disorders
Authors: Botía Juan A. , Guelfi Sebastian , Zhang David , D’Sa Karishma , Reynolds Regina , Onah Daniel , McDonagh Ellen M. , Martin Antonio Rueda , Tucci Arianna , Rendon Augusto , Houlden Henry , Hardy John , Ryten Mina
Published: March 2018

To facilitate precision medicine and neuroscience research, we developed a machine-learning technique that scores the likelihood that a gene, when mutated, will cause a neurological phenotype. We analysed 1126 genes relating to 25 subtypes of Mendelian neurological disease defined by Genomics England (March 2017) together with 154 gene-specific features capturing genetic variation, gene structure and tissue-specific expression and co-expression. We randomly re-sampled genes with no known disease association to develop bootstrapped decision-tree models, which were integrated to generate a decision tree-based ensemble for each disease subtype. Genes generating larger numbers of distinct transcripts and with higher probability of having missense mutations in normal individuals were significantly more likely to cause neurological diseases. Using mouse-mutant phenotypic data we tested the accuracy of gene-phenotype predictions and found that for 88% of all disease subtypes there was a significant enrichment of relevant phenotypic abnormalities when predicted genes were mutated in mice and in many cases mutations produced specific and matching phenotypes. Furthermore, using only newly identified genes included in the Genomics England November 2017 release, we assessed our gene-phenotype predictions and showed an 8.3 fold enrichment relative to chance for correct predictions. Thus, we demonstrate both the explanatory and predictive power of machine-learning-based models in neurological disease.
Current production as a rapid response expression reporter under micro-oxic and anoxic conditions
Authors: Madsen Cody , Barvo Noelia , Fromwiller Ciara , Tyll Serenity , Amburn Brian , Ducat Danny , Hamberger Bjoern , TerAvest Michaela A.
Published: March 2018

Inducible gene expression is crucial for regulating cellular processes and production of compounds within cellular pathways. Yet, inducing gene expression is only the first step to utilizing cellular processes for an applied purpose such as biosensors. Detecting when gene expression occurs is central to understanding the overall mechanism of the process as well as maximizing the process. Fluorescent proteins have been established as the primary tool for detecting gene expression in inducible systems. This study proposes electricity production as an alternate tool in reporting gene expression. Using a model organism for electricity production, Shewanella oneidensis MR-1, current was shown to be an efficient reporter for gene expression and comparable to superfolder green fluorescent protein (GFP). Through regulation of the lac operator and T7 promoter, current production was induced by isopropyl β-D-1-thiogalactopyranoside (IPTG) addition. IPTG addition induced translation of GFP and the MtrB protein, which complemented a ∆mtrB strain of S. oneidensis MR-1 and restored current production. This inducible system generated reproducible current in 18 minutes in both micro-oxic and anoxic conditions. These results show that current is a fast reporter for gene expression.

Financial Disclosure

The team was supported by the following departments and colleges at Michigan State University: College of Natural Science, College of Engineering, Biochemistry and Molecular Biology Department and Plant Research Laboratory. The team also received support from the DOE Great Lakes Bioenergy Research Center (DOE Office of Science BER DE-FC02-07ER64494) and startup funding from the Department of Molecular Biology and Biochemistry, Michigan State University and support from Michigan State University AgBioResearch (MICL02454) (to B.H.). This work was also supported by NSF CAREER (Award #1254238) to T.A.W. MSU Alpha Chi Sigma also supported the team.

Competing Interests

The authors declare that no competing interests exist.

Ethics Statement

N/A

Data Availability

All data will be supplied upon request by the corresponding author.

This work was assessed during the iGEM/PLOS Realtime Peer Review Jamboree on 23rd February 2018 and has been revised in response to the reviewers’ comments.
Differences between the de novo proteome and its non-functional precursor can result from neutral constraints on its birth process, not necessarily from natural selection alone
Authors: Nielly-Thibault Lou , Landry Christian R
Published: March 2018

Proteins are among the most important constituents of biological systems. Because all proteins ultimately evolved from previously non-coding DNA, the properties of these non-coding sequences and how they shape the birth of novel proteins are also expected to influence the organization of biological networks. When trying to explain and predict the properties of novel proteins, it is of particular importance to distinguish the contributions of natural selection and other evolutionary forces. Studies in the field typically use non-coding DNA and GC-content-based random-sequence models to generate random expectations for the properties of novel functional proteins. Deviations from these expectations have been interpreted as the result of natural selection. However, interpreting such deviations requires a yet-unattained understanding of the raw material of de novo gene birth and its relation to novel functional proteins. We mathematically show how the importance of the “junk” polypeptides that make up this raw material goes beyond their average properties and their filtering by natural selection. We find that the mean of any property among novel functional proteins also depends on its variance among junk polypeptides and its correlation with their rate of evolutionary turnover. In order to exemplify the use of our general theoretical results, we combine them with a simple model that predicts the means and variances of the properties of junk polypeptides from the genomic GC content alone. Under this model, we predict the effect of GC content on the mean length and mean intrinsic disorder of novel functional proteins as a function of evolutionary parameters. We use these predictions to formulate new evolutionary interpretations of published data on the length and intrinsic disorder of novel functional proteins. This work provides a theoretical framework that can serve as a guide for the prediction and interpretation of past and future results in the study of novel proteins and their properties under various evolutionary models. Our results provide the foundation for a better understanding of the properties of cellular networks through the evolutionary origin of their components.
On the variability of Species Abundance Distributions with trophic guild and community structure
Authors: García-Callejas David
Published: March 2018

Species Abundance Distributions (SADs) are one of the most studied properties of ecological communities, and their variability has been studied mostly in the context of horizontal communities, i.e. sets of species from a particular trophic guild. However, virtually all ecological communities encompass several trophic guilds, and the trophic interactions between them are key for explaining the persistence and abundance of individual species. Here I ask whether trophic interactions are also important in shaping Species Abundance Distributions of the different guilds of a community. I analyze the variation in SAD shape across trophic guilds in model and empirical communities. For that, I use a theoretical model that allows tracking the variations in abundances across trophic levels. The relationship between SAD shape and (1) trophic level, and (2) degree of predator specialization is analyzed using mixed-effect models. I combine this approach with an analysis of 4676 empirical datasets spanning terrestrial, marine and freshwater habitats, for which the variation in SAD shape is related to (1) trophic guild, and (2) habitat type. The evenness of model SADs is positively correlated to the trophic level of the guild considered, and also to the number of prey species per predator. These findings are confirmed by the empirical data: there is a significant relationship between SAD evenness and trophic guild, whereby primary producers display the most uneven SADs and pure carnivores the most even ones. Furthermore, regardless of trophic guild, SADs from marine habitats are the most even ones, with terrestrial SADs being the most uneven.
Small non-coding RNA expression in developing mouse nephron progenitor cells
Authors: Phua Yu Leng , Clugston Andrew , Chen Kevin Hong , Kostka Dennis , Ho Jacqueline
Published: March 2018

MicroRNAs (miRNAs) are small non-coding RNAs that are essential for the regulation of gene expression and play critical roles in human health and disease. Here we present comprehensive miRNA profiling data for mouse nephron progenitors, which give rise to most of the cell-types of the nephron, the functional units of the kidney. We describe a miRNA expression profile for nephron progenitors, with 162 miRNAs differentially expressed in nephron progenitors when compared to whole kidney. We also annotated 52, and experimentally validated 4 novel miRNAs, which are expressed in developing kidney. Our data is available as a public resource, so that it can be integrated into future studies and analyzed in the context of other functional and epigenomic data in kidney development. Specifically, it will be useful in the effort to shed light on molecular mechanisms underlying processes essential for normal kidney development, such as nephron progenitor specification, self-renewal and differentiation.
Apparent oxygen half saturation constant for nitrifiers: genus specific, inherent physiological property, or artefact of colony morphology?
Authors: Law Yingyu , Matysik Artur , Chen Xueming , Thi Sara Swa , Nguyen Thi Quynh Ngoc , Qiu Guang Lei , Natarajan Gayathri , Williams Rohan B.H. , Ni Bing-Jie , Seviour Thomas William , Wuertz Stefan
Published: March 2018

We report that a singleNitrospirasublineage I OTU performs nitrite oxidation in several full-scale domestic wastewater treatment plants (WWTPs) in the tropics (29-31 °C). Contrary to the prevailing theory for the relationship between nitrite oxidizing bacteria (NOB) and ammonia oxidizing bacteria (AOB), members of theNitrospirasublineage I OTU had an apparent half saturation coefficient,Ks(app)lower than that of the full-scale domestic activated sludge cohabitant AOB (0.09 ± 0.02 g O2 m−3versus 0.3 ± 0.03 g O2 m−3). Paradoxically, NOB may thus thrive under conditions of low oxygen supply. Low dissolved oxygen (DO) conditions could enrich for and high aeration inhibit the NOB in a long-term lab-scale reactor. The relative abundance ofNitrospiragradually decreased with increasing DO until it was washed out. Nitritation was sustained even after the DO was lowered subsequently. Based on 3D-fluorescencein situhybridization (FISH) image analysis, the morphologies of AOB and NOB microcolonies responded to DO levels in accordance with their apparent oxygen half saturation constantKs(app). When exposed to the same oxygenation level, NOB formed densely packed spherical clusters with a low surface area-to-volume ratio compared to theNitrosomonas-like AOB clusters, which maintained a porous and non-spherical morphology. Microcolony morphology is thus a way for AOB and NOB to regulate oxygen exposure and sustain the mutualistic interaction. However, short-term high DO exposure can select for AOB and against NOB in full-scale domestic WWTPs and such population dynamics depend on which specific AOB and NOB species predominate under given environmental conditions.
Oblique plane single-molecule localization microscopy for thick samples
Authors: Kim Jeongmin , Wojcik Michal , Wang Yuan , Xu Ke , Zhang Xiang
Published: March 2018

We introduce single-molecule oblique plane microscopy (obSTORM) to directly image oblique sections of thick samples into depth without lengthy axial stack acquisition. Using oblique light-sheet illumination and oblique fluorescence detection, obSTORM offers uniform super-resolution throughout imaging depth in diverse biological specimens from cells to tissues. In particular, we demonstrate an isotropic resolution of ∼51 nm over a depth of 32 μm for a tissue sample, and comparable resolution over a depth of 100 μm using fluorescent beads.
MRI2MRI: A deep convolutional network that accurately transforms between brain MRI contrasts
Authors: Xiao Sa , Wu Yue , Lee Aaron Y. , Rokem Ariel
Published: March 2018

Different brain MRI contrasts represent different tissue properties and are sensitive to different artifacts. The relationship between different contrasts is therefore complex and nonlinear. We developed a deep convolutional network that learns the mapping between different MRI contrasts. Using a publicly available dataset, we demonstrate that this algorithm accurately transforms between T1- and T2-weighted images, proton density images, time-of-flight angiograms, and diffusion MRI images. We demonstrate that these transformed images can be used to improve spatial registration between MR images of different contrasts.
Sequential regulatory activity prediction across chromosomes with convolutional neural networks
Authors: Kelley David R. , Reshef Yakir A. , Bileschi Maxwell , Belanger David , McLean Cory Y. , Snoek Jasper
Published: March 2018

Models for predicting phenotypic outcomes from genotypes have important applications to understanding genomic function and improving human health. Here, we develop a machine-learning system to predict cell-type–specific epigenetic and transcriptional profiles in large mammalian genomes from DNA sequence alone. By use of convolutional neural networks, this system identifies promoters and distal regulatory elements and synthesizes their content to make effective gene expression predictions. We show that model predictions for the influence of genomic variants on gene expression align well to causal variants underlying eQTLs in human populations and can be useful for generating mechanistic hypotheses to enable fine mapping of disease loci.
Comprehensive genomic profiling aids in treatment of a metastatic endometrial cancer
Authors: Dhami Jatinder , Hirshfield Kim M. , Ganesan Shridar , Hellmann Mira , Rojas Veronica , Amorosa Judith K. , Riedlinger Gregory M. , Zhong Hua , Ali Siraj M. , Pavlick Dean , Elvin Julia A. , Rodriguez-Rodriguez Lorna
Published: March 2018

FGFR-TACC fusions, including FGFR3-TACC3, have been identified as potential oncogenic drivers and actionable alterations in a number of different cancer types. The clinical relevance of FGFR3-TACC3 fusions in endometrial cancer has not yet been described. Formalin-fixed, paraffin-embedded metastatic endometrial carcinoma from the spleen and peritoneum were sent for comprehensive genomic profiling (CGP) using the FoundationOne platform as part of a prospective tumor genomic profiling protocol. We report the identification of an FGFR3-TACC3 fusion in a case of metastatic endometrioid endometrial cancer. Other potentially actionable alterations detected in this specimen included PIK3CA T1025S and an uncharacterized rearrangement involving TSC2. The patient initially received an FGFR inhibitor as an investigational agent and experienced stable disease with complete resolution of a pelvic nodule; however, treatment had to be discontinued because of intolerable side effects. A PET/CT scan nearly 3 mo after discontinuation showed disease progression. She subsequently received the mTOR inhibitor, temsirolimus, later accompanied by letrozole, and achieved stable disease. Clinical benefit was attributed to the mTOR inhibitor as tumor stained negative for estrogen receptor. Temsirolimus was discontinued after >17 mo because of disease progression. FGFR inhibitors may have clinical benefit in the treatment of endometrial carcinoma with FGFR3-TACC3 fusions. Additionally, clinical benefit from an mTOR inhibitor may reflect a response to targeting the alteration in PIK3CA or TSC2. More research is needed to understand the activity of FGFR3-TACC3 fusions on tumors and to discover additional therapeutic options for endometrial carcinoma patients with this gene fusion.
Hybrid modelling of a high-power X-ray attenuator plasma
Authors: Martín Ortega Álvaro , Lacoste Ana , Minea Tiberiu
Published: March 2018

X-ray gas attenuators act as stress-free high-pass filters for synchrotron and free-electron laser beamlines to reduce the heat load in downstream optical elements without affecting other properties of the X-ray beam. The absorption of the X-ray beam triggers a cascade of processes that ionize and heat up the gas locally, changing its density and therefore the X-ray absorption. Aiming to understand and predict the behaviour of the gas attenuator in terms of efficiencyversusgas pressure, a hybrid model has been developed, combining three approaches: an analytical description of the X-ray absorption; Monte Carlo for the electron thermalization; and a fluid treatment for the electron diffusion, recombination and excited-states relaxation. The model was applied to an argon-filled attenuator prototype built and tested at the European Synchrotron Radiation Facility, at a pressure of 200 mbar and assuming stationary conditions. The results of the model showed that the electron population thermalizes within a few nanoseconds after the X-ray pulse arrival and it occurs just around the X-ray beam path, recombining in the bulk of the gas rather than diffusing to the attenuator walls. The gas temperature along the beam path reached 850 K for 770 W of incident power and 182 W m−1of absorbed power. Around 70% of the absorbed power is released as visible and UV radiation rather than as heat to the gas. Comparison of the power absorption with the experiment showed an overall agreement both with the plasma radial profile and power absorption trend, the latter within an error smaller than 20%. This model can be used for the design and operation of synchrotron gas attenuators and as a base for a time-dependent model for free-electron laser attenuators.
Quantitative study of the influence of swimming therapy on osteoporosis rat models based on synchrotron radiation computed tomogaphy
Authors: Huang Liya , Xu Jun , Guo Han , Wang Yujie , Zhao Jun , Sun Jianqi
Published: March 2018

Osteoporosis is a bone disease with a variety of causes, leading to bone pain and fragility to fracture. Major treatment methods include nutrition therapy, exercise therapy, drug therapy and surgical treatment, among which exercise therapy, such as swimming, is the most effective. To investigate the optimal swimming therapy regime for postmenopausal women, the effects of eight weeks of different intensity swimming exercises were studied in rat models. After the swimming program, lumbar vertebrae were dissected from all the rats and scanned by synchrotron radiation computed tomography (SRCT). Histomorphometry analysis and finite-element analysis were carried out on the trabecular structure of the L4 lumbar based on the acquired SRCT slices. Histomorphometry analysis showed that swimming can alleviate the decrease in bone strength induced by estrogen deficiency, and moderate-intensity swimming was found to have the most significant effect.
Pulse intensity characterization of the LCLS nanosecond double-bunch mode of operation
Authors: Sun Yanwen , Decker Franz-Josef , Turner James , Song Sanghoon , Robert Aymeric , Zhu Diling
Published: March 2018

The recent demonstration of the `nanosecond double-bunch' operation mode,i.e.two X-ray pulses separated in time between 0.35 and hundreds of nanoseconds and by increments of 0.35 ns, offers new opportunities to investigate ultrafast dynamics in diverse systems of interest. However, in order to reach its full potential, this mode of operation requires the precise characterization of the intensity of each X-ray pulse within each pulse pair for any time separation. Here, a transmissive single-shot diagnostic that achieves this goal for time separations larger than 0.7 ns with a precision better than 5% is presented. It also provides real-time monitoring feedback to help tune the accelerator parameters to deliver double pulse intensity distributions optimized for specific experimental goals.
The crystal structure of [Fe2(PIMIC6)(AnthCO2)(CH3CN)]·[Fe2(PIMIC6)(AnthCO2)(CH3CN)0.9(CH2Cl2)0.1]·[Fe2(PIMIC6)(AnthCO2)(OH2)]·0.75CH3CN: a crystallographer's nightmare or a fascinating case of disorder?
Authors: Becker Sabine
Published: March 2018

Refinement of large crystal structures as well as that of disordered structures can be challenging. If both features come together, structure refinement has the potential of becoming a crystallographer's nightmare. Here, the refinement of the large and highly disordered structure of [Fe2(PIMIC6)(AnthCO2)(CH3CN)]·[Fe2(PIMIC6)(AnthCO2)(CH3CN)0.9(CH2Cl2)0.1]·[Fe2(PIMIC6)(AnthCO2)(OH2)]·0.75CH3CN [(1), PIMIC6 is a phenol–imine-based macrocycle, AnthCO2is an anthracene acid anion] is described and discussed. A total of 5311 parameters had to be refined to generate a model that allows for 14 400 possible arrangements of (1) in the asymmetric unit, making this structure one of the most complex structures in the Cambridge Structural Database to date. All disorders are exceptionally well resolved and exhaustive parameterizing affords a refinement model that is unique with respect to the detail of disorder refinement.
N,N-Dimethyl-2-[(1E)-({[(methylsulfanyl)methanethioyl]amino}imino)methyl]aniline
Authors: Sohtun Winaki P. , Kannan Arunachalam , Dhandayutham Saravanan , Velusamy Marappan
Published: March 2018

In the title compound, C11H15N3S2, the dithiocarbazate moiety is rotated by 18.73 (8)° with respect to the benzene ring. The dithiocarbazate group adopts anEconfiguration with respect to the C=N bond of the benzylidene group. Furthermore, in the solid state the compound exists in the thione tautomeric form. In the crystal, molecules are linked by pairs of weak N—H...S hydrogen bonds, forming inversion dimers which are arranged in layers parallel to (010).
International business research challenges in Africa
Authors: Ado Abdoulkadre , Wanjiru Roseline
Published: March 2018

Purpose

This paper aims to explore the challenges researchers in/on Africa face when conducting research on the continent. It examines the reasons behind Africans’ relatively limited contribution to the business literature in the global sphere and why not culturally sensitive and nuanced research on Africa is spreading unchallenged.

Design/methodology/approach

The study combines knowledge creation and institutional theories to explain why African business scholars struggle in researching the continent and in contributing significantly to global knowledge creation. It also explores the debate about why Africa’s narratives in business seem dominated by not culturally sensitive and nuanced voices and approaches. It uses a participant observation method.

Findings

The study found that African scholars have not yet contributed significantly to global knowledge creation because of Africa’s institutional weaknesses and lack of government support for research, coupled with challenges at the interviewing, organizational and scholars’ levels. The study points to the specificities of the continent as well as to African interviewees’ particularities and the type of interactions with the researchers. The paper proposes new avenues to address those multilevel challenges and offers key lessons for future studies.

Originality/value

To the best of the authors’ knowledge, this study is the first to systematically investigate the fundamental reasons behind business research challenges in/on Africa from knowledge creation and institutional standpoints. This study also contributes to the growing debate on Africans’ meager contribution to business literature as well as the controversy regarding culturally sensitive vs not culturally sensitive knowledge creation on Africa. Finally, it proposes avenues to understanding and overcoming those challenges.