bluuebunny/crossref_metadata_2025 huggingface dataset:
Author Disclosures in Plastic Surgery Journals Compared With Information Reported in the Open Payments Database: How Open Are We?
Authors: Boyll Piper , Neville Matthew , Bernard Robert , Mahabir Raman C
Published: September 2018

Background

Relationships between companies in the biomedical industry and authors submitting scientific articles for publication has been an issue of some concern for many years. It has been frequently demonstrated that these financial relationships can influence the manner in which research findings are presented. The National Physician Payment Transparency Program, also known as the Open Payment Program or the Sunshine Act, was legislated to expose potential conflicts of interest (COIs). Likewise, most peer-reviewed journals require disclosure of any potential COIs.

Objectives

The purpose of this paper was to compare the information published in the Open Payment Database to authors’ self-disclosed COIs in their published articles.

Methods

An analysis was performed by one of the authors (P.S.B.) of all articles published in Aesthetic Surgery Journal (ASJ) and Plastic and Reconstructive Surgery (PRS) from August 2013 through December 2016. Financial disclosures reported in these articles were compared with the physician payment information provided by the biomedical industry and published in the Open Payments Database in 2013 and 2018.

Results

A total of 1346 articles were included in the study, from which 320 authors and 899 total authorships were eligible for analysis. Out of 782 authorships with noted discrepancies, 96% were related to potential COIs found in the Open Payments database but not disclosed in the journal publication.

Conclusions

Our data suggest major discordance between authors’ self-reported COIs in the plastic surgery literature and industry payments published in the Open Payments database.
Glucomannan Hydrolysate Promotes Gut Proliferative Homeostasis and Extends Life Span in Drosophila melanogaster
Authors: Si Yuan , Liu Xi , Ye Kaixiong , Bonfini Alessandro , Hu Xun Yang , Buchon Nicolas , Gu Zhenglong
Published: September 2018

Dietary supplementation of glucomannan has been shown to have multiple health benefits, but its effect on life span has not been investigated. Here, we show that glucomannan hydrolysate (GMH) treatment extends mean life span of the model organism Drosophila melanogaster. To unravel the underlying mechanisms, we first examined the effect of GMH on the gut microbiota. We found that GMH treatment is associated with an elevated bacterial load in aged flies but overall has limited effects on the relative microbiota composition. We also demonstrated that GMH inhibits age-associated hyperproliferation of intestinal stem cells and thus delays the deterioration of gut integrity. Further analysis of the midgut transcriptome revealed that both EGFR/MAPK and JAK/STAT signaling pathways are suppressed in GMH groups. Multiple key regulators or effectors of EGFR/MAPK pathway, Ets21c, Mkp3, and Rho, are downregulated by GMH treatment. In the JAK/STAT pathway, major ligands (eg, Upd2 and Upd3) and negative feedback inhibitors (eg, Socs36e) are all significantly downregulated. Additionally, the expression of genes encoding antimicrobial peptides is elevated by GMH treatment. Taken together, our study shows that dietary supplementation of GMH can prolong life span, possibly through regulating gut proliferative homeostasis.
The Impact of Reactogenicity After the First Dose of Recombinant Zoster Vaccine on the Physical Functioning and Quality of Life of Older Adults: An Open-Label, Phase III Trial
Authors: Schmader Kenneth E , Levin Myron J , Grupping Katrijn , Matthews Sean , Butuk David , Chen Michael , Idrissi Mohamed El , Fissette Laurence A , Fogarty Charles , Hartley Paul , Klein Nicola P , Nevarez Max , Uusinarkaus Kari , Oostvogels Lidia , Curran Desmond
Published: September 2018

Background

Herpes zoster and its related complications are associated with significant medical burden, which negatively affects quality of life and daily functioning of the patients. The recently licensed recombinant zoster vaccine (RZV) offers high efficacy but is associated with local and systemic reactions. This study assessed the impact of RZV on the quality of life and daily functioning of participants and implications for caregivers.

Methods

Four hundred and one adults aged 50 years or older received single RZV doses at 0 and 2 months in this open-label, single-arm, multicenter study (NCT02979639). Change in mean SF-36 Physical Functioning score following first-dose administration, quality of life, reactogenicity, safety, productivity loss, and health care resource utilization was assessed. The current analysis was performed post-vaccine dose-1; safety follow-up will continue until 1 year post-dose-2.

Results

The most common solicited local symptoms were injection-site pain (77.5%), redness (23.0%), and swelling (13.3%); the most frequent solicited systemic reactions were fatigue (33.5%), headache (28.3%), and myalgia (26.8%). Grade 3 reactogenicity occurred in 9.5% of participants and was associated with a transient clinically important decrease in SF-36 Physical Functioning score (affecting activities such as walking, carrying groceries, climbing stairs) on Days 1 and 2 post-first vaccination. No clinically meaningful reductions in mean SF-36 Physical Functioning scale scores from pre- to post-RZV dose-1 were observed (mean +1.9 points, primary end point), and no overall quality-adjusted-life-year loss was recorded post-dose-1. Five participants reported lost workdays; caregiver workload was not increased.

Conclusions

Overall, the physical functioning and quality of life of older adults were not affected by a first RZV dose. The observed reactogenicity was consistent with previous studies.
Evaluation of Frailty as an Unmeasured Confounder in Observational Studies of Antidiabetic Medications
Authors: Presley Caroline A , Chipman Jonathan , Min Jea Young , Grijalva Carlos G , Greevy Robert A , Griffin Marie R , Roumie Christianne L
Published: September 2018

Background

It is unknown whether observational studies evaluating the association between antidiabetic medications and mortality adequately account for frailty. Our objectives were to evaluate if frailty was a potential confounder in the relationship between antidiabetic medication regimen and mortality and how well administrative and clinical electronic health record (EHR) data account for frailty.

Methods

We conducted a retrospective cohort study in a single Veterans Health Administration (VHA) healthcare system of 500 hospitalizations—the majority due to heart failure—of Veterans who received regular VHA care and initiated type 2 diabetes treatment from 2001 to 2008. We measured frailty using a modified frailty index (FI, >0.21 frail). We obtained antidiabetic medication regimen and time-to-death from administrative sources. We compared FI among patients on different antidiabetic regimens. Stepwise Cox proportional hazards regression estimated time-to-death by demographic, administrative, clinical EHR, and FI data.

Results

Median FI was 0.22 (interquartile range 0.18, 0.27). Frailty differed across antidiabetic regimens (p < .001). An FI increase of 0.05 was associated with an increased risk of death (hazard ratio 1.45, 95% confidence interval 1.32, 1.60). Cox proportional hazards model for time-to-death including demographic, administrative, and clinical EHR data had a c-statistic of 0.70; adding FI showed marginal improvement (c-statistic 0.72).

Conclusions

Frailty was associated with antidiabetic regimen and death, and may confound that relationship. Demographic, administrative, and clinical EHR data, commonly used to balance differences among exposure groups, performed moderately well in assessing risk of death, with minimal gain from adding frailty. Study design and analytic techniques can help minimize potential confounding by frailty in observational studies.
Communication and Distributed Work
Authors: ter Hoeven Claartje , Gibbs Jennifer
Published: September 2018

Scholars have been studying distributed work since the 1990s. The proliferation of new communication technologies such as e-mail, computer conferencing, instant messaging, and enterprise social media has enabled and made commonplace geographically dispersed work arrangements such as global virtual teams, mobile work, and telework that span time and space and allow for collaboration at a distance. While distributed work is an interdisciplinary topic that is studied by scholars in management, information systems, and communication (among others), this review is bounded to focus primarily on research by communication scholars or in dealing with communication phenomena. Distributed work is of great interest to communication scholars as it highlights how communication processes such as collaboration, knowledge sharing, and relationship formation are enacted across geographical, temporal, cultural, and organizational boundaries.
The U.S. Mexican War
Authors: Conway Christopher
Published: September 2018

The US-Mexican War of 1846–1848 was key to the drawing of the modern borders of the United States and Mexico, and it contributed to the coming of the Civil War in the United States. At the end of the war, after the signing of The Treaty of Guadalupe Hidalgo (1848), the United States acquired the present day states of California, Nevada, Arizona, Utah, and New Mexico, as well as parts of Wyoming, Kansas, and Colorado. (The US had annexed the Republic of Texas before the war, in 1845.) For this reason, the war paved the way for the emergence of a multicultural western and southwestern United States populated by Native peoples and Mexicans who had lived there for generations. The acquisition of so much new territory also intensified tensions in the United States over where to draw the line between slave states and free states. In 1820, thanks to the Missouri Compromise, which stipulated that slavery would not be allowed above the southern border of Missouri, Whigs and Democrats achieved an equilibrium of twelve slave states and twelve free states. The acquisition of Texas, which was south of Missouri’s border, tipped the scale in favor of the slave-owning states. However, the Missouri Compromise was not equipped to explain what to do with the newly acquired lands to the west, leading to the Compromise of 1850 and the Kansas-Nebraska Act of 1854, both which negotiated the future expansion of slavery. In Mexico, the humiliation of defeat stirred liberal nationalism and helped to discredit Mexican president Antonio López de Santa Anna, who was overthrown in 1855. The war thus marked the birth of modern Mexican liberalism, which remained a potent force until the Mexican Revolution of 1910. These various repercussions underline why the US-Mexican War is more than a bounded, historical event. It would be more accurate to describe it as a lens through which to examine political debates about slavery in the United States, the emergence of a “Mexican American” population within US borders, the realization of the Anglo-American ideology of Manifest Destiny, and the emergence of modern Mexican nationalism and liberalism.
The Rio Grande
Authors: Lavariega Monforti Jessica , Graham Margaret A.
Published: September 2018

The Rio Grande is a 1,900-mile-long river that has been a lifeline for communities that depend on its waters for sustenance and transportation in a predominantly arid or semi-arid environment. The source of the river is in the San Juan Mountains of south-central Colorado. It flows east and then south through New Mexico and eventually opens into the Gulf of Mexico at the southernmost tip of Texas. Below the sister cities of El Paso, Texas, and Ciudad Juarez, Chihuahua, the Rio Grande has formed the international boundary between the United States and Mexico since the Treaty of Guadalupe Hidalgo relocated the border in 1848. The river’s importance as a life-sustaining resource is reflected in its many names: Río del Norte, Río Bravo del Norte, or Río Bravo in Mexico; P’osoge (“Big River”) by the Pueblo Tewa; and Tó Ba’áadi (“Female River,” because its course is southerly) by the Navajo. In 1582 the Spanish explorer Antonio de Espejo followed the course of the Río Conchos to its confluence with a great river, which Espejo named Río del Norte (River of the North). The name Río Grande was first given by the explorer Juan de Oñate, who arrived on its banks near present-day El Paso in 1598. This work focuses on the Rio Grande as border and borderland. Like the river itself, the border moves physically, historically, politically, and socially, and the meanings of the border, and of the river that denotes it, have also shifted. This life-giving border river has a long history of conflict and is today, in many locations, a militarized zone with multiple layers of surveillance by local, state, and federal authorities. Portrayals of crime, violence, and state control are popular in the media, but they often do not include the lived experience of many border residents. The English novelist Emma Smith wrote, “The river is used to divide but it is not an impenetrable division. Life is like the river, sometimes it sweeps you gently along and sometimes the rapids come out of nowhere.”
The Beneficial Root-Colonizing Fungus Mortierella hyalina Promotes the Aerial Growth of Arabidopsis and Activates Calcium-Dependent Responses That Restrict Alternaria brassicae–Induced Disease Development in Roots
Authors: Johnson Joy Michal , Ludwig Anatoli , Furch Alexandra C. U. , Mithöfer Axel , Scholz Sandra , Reichelt Michael , Oelmüller Ralf
Published: September 2018

The endophytic fungus Mortierella hyalina colonizes the roots of Arabidopsis thaliana and stimulates growth and biomass production of the aerial parts but not of roots. An exudate fraction from the fungus induces rapid and transient cytoplasmic Ca2+elevation in the roots. The Ca2+ response does not require the well-characterized (co)receptors BAK1, CERK1, and FLS2 for pathogen-associated molecular patterns, and the Ca2+ channels GLR-2.4, GLR-2.5, and GLR-3.3 or the vacuolar TWO PORE CHANNEL1, which might be involved in cytoplasmic Ca2+ elevation. We isolated an ethyl-methane-sulfonate–induced Arabidopsis mutant that is impaired in this Ca2+ response. The roots of the mutant are impaired in M. hyalina–mediated suppression of immune responses after Alternaria brassicae infection, i.e., jasmonate accumulation, generation of reactive oxygen species, as well as the activation of jasmonate-related defense genes. Furthermore, they are more colonized by M. hyalina than wild-type roots. We propose that the mutant gene product is involved in a Ca2+-dependent signaling pathway activated by M. hyalina to suppress immune responses in Arabidopsis roots.
Interactions Between Root Rotting Phytophthora, Abies Christmas Trees, and Environment
Authors: McKeever Kathleen M. , Chastagner Gary A
Published: September 2018

Defining host-pathogen interactions between species of root-rotting Phytophthora and Abies in Christmas tree production areas is important for tailoring management activities on a regional scale and for developing molecular tools for identifying resistant host species. Classifying Abies species as resistant or susceptible is complicated by regional variation in abundance and aggressiveness of Phytophthora species and the influence of environment on symptom expression and host vigor. Because previous studies performed to assess host response to Phytophthora root rot (PRR) have focused on one or a few species of either the host or pathogen, a multifactorial experiment was conducted to assess the responses of seven species of Abies challenged with three isolates each of four Phytophthora species under contrasting temperature conditions. Evaluation of mortality, root rot severity, and remaining root biomass after 16 weeks of exposure to the pathogen confirmed prior inferences regarding inherent variation in the resistance responses of various species of Abies and demonstrated evidence of variation in aggressiveness among species of Phytophthora as well as different isolates of the same Phytophthora species. The ambient temperatures at which studies were conducted had a conspicuous effect on host mortality, root rot severity, and radial growth of Phytophthora. Understanding how host responses differ under variable pathogen attack and ambient environment will improve efforts to control PRR using host species substitutions on infested ground.
Genetic Diversity of Verticillium dahliae Populations From Olive and Potato in Lebanon
Authors: Baroudy Farah , Putman Alexander I. , Habib Wassim , Puri Krishna D. , Subbarao Krishna V. , Nigro Franco
Published: September 2018

Verticillium dahliae is widely distributed in potato and olive fields in Lebanon, causing serious economic losses. However, little is known about the inoculum source, population structure, and genetic diversity of the pathogen or the mechanisms of dissemination within Lebanon. To understand the population structure, a total of 203 isolates sampled from olive (n = 78) and potato (n = 125) were characterized for species, mating type, and race, and the genetic relationships were delineated using 13 microsatellite markers. All isolates except one from potato were V. dahliae, with 55.1 and 12.1% race 1, and 43.6 and 83.1% race 2 in olive and potato, respectively. The genetic structure of the studied population was best described by two large and two small clusters. Membership in the two large clusters was determined by the presence or absence of the effector gene Ave1. Furthermore, genetic structure was moderately associated with the host of origin but was weakly associated with the geographic origin. All but four isolates represented by three multilocus haploid genotypes were MAT1-2. This study identified a clear lack of gene flow between virulence genotypes of V. dahliae despite the proximity of these cropping systems and the wide distribution of genetic diversity among hosts and geographic regions in Lebanon.
Comparative Studies on the Effect of Adjuvants with Urea to Reduce the Overwintering Inoculum of Venturia inaequalis
Authors: Beckerman Janna , Abbott Chelsi
Published: September 2018

A 2-year study on the use of organic and conventional adjuvants alone, or mixed with urea, was conducted for management of overwintering inoculum of the apple scab pathogen, Venturia inaequalis. Select adjuvants (LI 700, Bond Max, Latron B-1956, and Organic Wet Betty [OWB]) have the potential to hasten urea-driven leaf litter decomposition and reduce V. inaequalis overwintering inoculum comparable to urea, and that one organic surfactant could perform the same level of leaf decomposition as urea. Combinations of adjuvants with urea significantly improved leaf litter degradation compared with urea alone, concomitant with reducing the number of pseudothecia present and pseudothecium fertility. We demonstrate that the combination of urea with Bond Max or OWB reduced pseudothecia fertility and ascospore production to less than 5% in the remaining pseudothecia, a significantly greater reduction than with urea alone. These results suggest that conventional growers combine urea with Bond Max or OWB to more effectively reduce overwintering inoculum, and that the adjuvant OWB can provide organic growers with comparable performance to urea used in conventional orchards for improved sanitation.
MYCN-induced metabolic rewiring creates novel therapeutic vulnerabilities in neuroblastoma
Authors: Tjaden Britta , Baum Katharina , Marquardt Viktoria , Simon Mareike , Trajkovic-Arsic Marija , Kouril Theresa , Siebers Bettina , Lisec Jan , Siveke Jens T. , Schulte Johannes H. , Benary Uwe , Remke Marc , Wolf Jana , Schramm Alexander
Published: September 2018

MYCN is a transcription factor that is aberrantly expressed in many tumor types and is often correlated with poor patient prognosis. Recently, several lines of evidence pointed to the fact that oncogenic activation of MYC family proteins is concomitant with reprogramming of tumor cells to cope with an enhanced need for metabolites during cell growth. These adaptions are driven by the ability of MYC proteins to act as transcriptional amplifiers in a tissue-of-origin specific manner. Here, we describe the effects of MYCN overexpression on metabolic reprogramming in neuroblastoma cells. Ectopic expression of MYCN induced a glycolytic switch that was concomitant with enhanced sensitivity towards 2-deoxyglucose, an inhibitor of glycolysis. Moreover, global metabolic profiling revealed extensive alterations in the cellular metabolome resulting from overexpression of MYCN. Limited supply with either of the two main carbon sources, glucose or glutamine, resulted in distinct shifts in steady-state metabolite levels and significant changes in glutathione metabolism. Interestingly, interference with glutamine-glutamate conversion preferentially blocked proliferation of MYCN overexpressing cells, when glutamine levels were reduced. Thus, our study uncovered MYCN induction and nutrient levels as important metabolic master switches in neuroblastoma cells and identified critical nodes that restrict tumor cell proliferation.
Nicotinic and Cholinergic Modulation of Reward Prediction Error Computations in the Ventral Tegmental Area: a Minimal Circuit Model
Authors: Deperrois Nicolas , Gutkin Boris
Published: September 2018

Dopamine (DA) neurons in the ventral tegmental area (VTA) are thought to encode reward prediction errors (RPE) by comparing actual and expected rewards. In recent years, much work has been done to identify how the brain uses and computes this signal.While several lines of evidence suggest the the interplay of he DA and the inhibitory interneurons in the VTA implements the RPE computaiton, it still remains unclear how the DA neurons learn key quantities, for example the amplitude and the timing of primary rewards during conditioning tasks. Furthermore, exogenous nicotine and endogenous acetylcholine, acting on both VTA DA and GABA (γ- aminobutyric acid) neurons via nicotinic-acetylcholine receptors (nAChRs), also likely affect these computations. To explore the potential circuit-level mechanisms for RPE computations during classical-conditioning tasks, we developed a minimal computational model of the VTA circuitry. The model was designed to account for several reward-related properties of VTA afferents and recent findings on VTA GABA neuron dynamics during conditioning.

With our minimal model, we showed that the RPE can be learned by a two-speed process computing reward timing and magnitude. Including a model of nAChR-mediated currents in the VTA DA-GABA circuit, we also showed that nicotine should reduce the acetylcholine action on the VTA GABA neurons by receptor desensitization and therefore potentially boost the DA responses to reward information. Together, our results delineate the mechanisms by which RPE are computed in the brain, and suggest a hypothesis on nicotine-mediated effects on reward-related perception and decision-making.
Cell competition corrects noisy Wnt morphogen gradients to achieve robust patterning
Authors: Akieda Yuki , Ogamino Shohei , Furuie Hironobu , Ishitani Shizuka , Akiyoshi Ryutaro , Nogami Jumpei , Masuda Takamasa , Shimizu Nobuyuki , Ohkawa Yasuyuki , Ishitani Tohru
Published: September 2018

Morphogen signaling forms an activity gradient and instructs cell identities in a signaling strength-dependent manner to pattern developing tissues. However, developing tissues also undergo dynamic morphogenesis, which may produce cells with unfit morphogen signaling and consequent noisy morphogen gradient. Here we show that a cell competition-related system corrects such noisy morphogen gradients. Zebrafish imaging analyses of the Wnt/β-catenin signaling-gradient, which acts as a morphogen to establish embryonic anterior-posterior patterning, revealed that unfit cells with abnormal Wnt/β-catenin activity spontaneously appear and produce noise in the Wnt/β-catenin-gradient. Communication between the unfit and neighboring fit cells via cadherin proteins stimulates the apoptosis of the unfit cells by activating Smad signaling and reactive oxygen species production. This unfit cell elimination is required for proper Wnt/β-catenin-gradient formation and consequent anterior-posterior patterning. Because this gradient controls patterning not only in the embryo but also in adult tissues, this system may support tissue robustness and disease prevention.
Transsynaptic interactions between IgSF proteins DIP-α and Dpr10 are required for motor neuron targeting specificity inDrosophila
Authors: Ashley James , Sorrentino Violet , Nagarkar-Jaiswal Sonal , Tan Liming , Xu Shuwa , Xiao Qi , Zinn Kai , Carrillo Robert A.
Published: September 2018

TheDrosophilalarval neuromuscular system provides an ideal context in which to study synaptic partner choice, because it contains a small number of pre- and postsynaptic cells connected in an invariant pattern. The discovery of interactions between two subfamilies of IgSF cell surface proteins, the Dprs and the DIPs, provided new candidates for cellular labels controlling synaptic specificity. Here we show that DIP-α is expressed by two identified motor neurons, while its binding partner Dpr10 is expressed by postsynaptic muscle targets. Removal of either DIP-α or Dpr10 results in loss of specific axonal branches and NMJs formed by one motor neuron, MNISN-1s, while other branches of the MNISN-1s axon develop normally. The temporal and spatial expression pattern ofdpr10correlates with muscle innervation by MNISN-1s during embryonic development. We propose a model whereby DIP-α and Dpr10 on opposing synaptic partners interact with each other to generate proper motor neuron connectivity.
Dietary fatty acids promote lipid droplet diversity through seipin enrichment in an ER subdomain
Authors: Cao Zhe , Hao Yan , Lee Yiu Yiu , Wang Pengfei , Li Xuesong , Xie Kang , Lam Wen Jiun , Qiu Yifei , Shui Guanghou , Liu Pingsheng , Qu Jianan , Kang Byung-Ho , Mak Ho Yi
Published: September 2018

Exogenous metabolites from microbial and dietary origins have profound effects on host metabolism. Here, we report that a sub-population of lipid droplets (LDs), which are conserved organelles for fat storage, is defined by metabolites-driven targeting of theC. elegansseipin ortholog, SEIP-1. Loss of SEIP-1 function reduced the size of a subset of LDs while over-expression of SEIP-1 had the opposite effect. Ultrastructural analysis revealed SEIP-1 enrichment in an endoplasmic reticulum (ER) subdomain, which co-purified with LDs. Analyses ofC. elegansand bacterial genetic mutants indicated a requirement of polyunsaturated fatty acids (PUFAs) and microbial cyclopropane fatty acids (CFAs) for SEIP-1 enrichment, as confirmed by dietary supplementation experiments. In mammalian cells, heterologous expression of SEIP-1 promoted lipid droplet expansion from ER subdomains in a conserved manner. Our results suggest that microbial and polyunsaturated fatty acids serve unexpected roles in regulating cellular fat storage by enforcing LD diversity.
Metatranscriptomic and thermodynamic insights into medium-chain fatty acid production using an anaerobic microbiome
Authors: Scarborough Matthew J. , Lawson Christopher E. , Hamilton Joshua J. , Donohue Timothy J. , Noguera Daniel R.
Published: September 2018

Biomanufacturing from renewable feedstocks represents a sustainable strategy to offset fossil fuel-based chemical production. One potential biomanufacturing strategy is production of medium chain fatty acids (MCFA) from organic feedstocks using either pure cultures or microbiomes. While the set of microbes in a microbiome can often metabolize more diverse organic materials than a single species, and the role of specific species may be known, knowledge of the carbon and energy flow within and between organisms in MCFA producing microbiomes is only starting to emerge. Here, we integrate metagenomic, metatranscriptomic, and thermodynamic analyses to predict and characterize the metabolic network of an anaerobic microbiome producing MCFA from organic matter derived from lignocellulosic ethanol fermentation conversion residue. A total of 37 high quality (>80% complete, < 10% contamination) metagenome-assembled genomes (MAGs) were recovered from the microbiome and metabolic reconstruction of the 10 most abundant MAGs was performed. Metabolic reconstruction combined with metatranscriptomic analysis predicted that organisms affiliated with Lactobacillus and Coriobacteriaceae degraded carbohydrates and fermented sugars to lactate and acetate. Lachnospiraceae and Eubacteriaceae affiliated organisms were predicted to transform these fermentation products to MCFA. Thermodynamic analyses identified conditions in which H2 is expected to be either produced or consumed, suggesting a potential role of H2 partial pressure on MCFA production. From an integrated systems analysis perspective, we propose that MCFA production could be improved if microbiomes are engineered to use homofermentative instead of heterofermentative Lactobacillus, and if MCFA-producing organisms are engineered to preferentially use a thioesterase instead of a CoA transferase as the terminal enzyme in reverse β-oxidation.

Importance

Mixed communities of microbes play important roles in health, the environment, agriculture, and biotechnology. While tapping the combined activity of organisms within microbiomes may allow the utilization of a wider range of substrate over the use of pure cultures for biomanufacturing, harnessing the metabolism of these mixed cultures remains a major challenge. Here, we predict metabolic functions of bacteria in a microbiome that produces medium-chain fatty acids from a renewable feedstock. Our findings lay the foundation to begin addressing how to engineer and control microbiomes for improved biomanufacturing; to build synthetic mixtures of microbes that produce valuable chemicals from renewable resources; and to better understand microbial communities that contribute to health, agriculture, and the environment.
Precision identification and prediction of high mortality phenotypes and disease progression pathways in severe malaria without requiring longitudinal data
Authors: Hoffmann Till , Johnston Iain , Greenbury Sam , Cominetti Ornella , Jallow Muminatou , Kwiatkowski Dominic , Barahona Mauricio , Jones Nick , Casals-Pascual Climent
Published: September 2018

The parasite Plasmodium falciparum is the main cause of severe malaria (SM). Despite treatment with antimalarial drugs, more than 450,000 SM deaths are reported every year, mainly in African children. The diversity of clinical presentations associated with SM indicate important differences in disease pathogenesis that often require specific treatment, and this clinical heterogeneity of SM is largely unresolved. In this study, we apply new machine learning and inference tools for large-scale data analysis to dissect the heterogeneity in patterns of clinical features associated with SM in 2,695 Gambian children admitted to hospital with Plasmodium falciparum malaria. This quantitative analysis, including the powerful HyperTraPS algorithm for inference of progressive processes, reveals pathways of SM symptom progression and features predicting the severity of individual patient outcomes. Notably, our approach allows the identification and dissection of disease progression pathways without the need for longitudinal observations. Learning these pathways and features from this rich dataset allows us to construct several quantitative measures of the mortality risk associated with a patient presenting with a given set of symptoms. By independently surveying expert practitioners, we show that this data-driven approach agrees with and expands the current state of knowledge on malaria progression, while simultaneously providing a data-supported framework for predicting clinical risk.
Noninvasive prenatal test of methylmalonic academia cblC type through targeted sequencing of cell-free DNA in maternal plasma
Authors: Han Lianshu , Chen Chao , Guo Fengyu , Ye Jun , Peng Zhiyu , Qiu Wenjuan , Wang Yaoshen , Li Wei , Zhang Huiwen , Liang Lili , Wang Yu , Wang Huanhuan , Ji Xing , Sun Jun , Gu Xuefan
Published: September 2018

Methylmalonic acidemia (MMA) cblC type is the most frequent inborn error of intracellular cobalamin metabolism which is caused by mutations of MMACHC gene. Non-invasive test of MMA for pregnant women facilitates safe and timely prenatal diagnosis of the disease. In our study, we aimed to design and validate a haplotype-based noninvasive prenatal test (NIPT) method for cblC type of MMA. Targeted capture sequencing using customized hybridization was performed utilizing gDNA (genomic DNA) of trios including parents and an affected proband to determine parental haplotypes associated with the mutant and wild allele. The fetal haplotype was inferred later based on the high depth sequencing data of maternal plasma as well as haplotype linkage analysis. The fetal genotypes deduced by NIPT were further validated by amniocentesis. Haplotype-based NIPT was successfully performed in 21 families. The results of NIPT of 21 families were all consistent with invasive prenatal diagnosis, which was interpreted in a blinded fashion. Three fetuses were identified as compound heterozygosity of MMACHC, 9 fetuses were carriers of MMACHC variant, and 9 fetuses were normal. These results indicated that the haplotype-based NIPT for MMA through small target capture region sequencing is technically accurate and feasible.
Excised linear introns regulate growth in yeast
Authors: Morgan Jeffrey T. , Fink Gerald R. , Bartel David P.
Published: September 2018

Spliceosomal introns are ubiquitous non-coding RNAs typically destined for rapid debranching and degradation. Here, we describe 34 excisedSaccharomyces cerevisiaeintrons that, although rapidly degraded in log-phase growth, accumulate as linear RNAs under either saturated-growth conditions or other stresses that cause prolonged inhibition of TORC1, a key integrator of growth signaling. Introns that become stabilized remain associated with components of the spliceosome and differ from the other spliceosomal introns in having a short distance between their lariat branch point and 3′ splice site, which is necessary and sufficient for their stabilization. Deletion of these unusual introns is disadvantageous in saturated conditions and causes aberrantly high growth rates of yeast chronically challenged with the TORC1 inhibitor rapamycin. Reintroduction of native or engineered stable introns suppresses this aberrant rapamycin response. Thus, excised introns function within the TOR growth-signaling network ofS. cerevisiae, and more generally, excised spliceosomal introns can have biological functions.
Glial Ca2+ Signaling Links Endocytosis to K+ Buffering around Neuronal Somas to Regulate Excitability
Authors: Weiss Shirley , Melom Jan E , Ormerod Kiel G , Zhang Yao V , Littleton J Troy
Published: September 2018

Glial-neuronal signaling at synapses is widely studied, but how glia interact with neuronal somas to regulate neuronal function is unclear. Drosophila cortex glia are restricted to brain regions devoid of synapses, providing an opportunity to characterize interactions with neuronal somas. Mutations in the cortex glial NCKXzydeco elevate basal Ca2+, predisposing animals to seizures. To determine how cortex glial Ca2+ signaling controls neuronal excitability, we performed an in vivo modifier screen of the NCKXzydeco seizure phenotype. We show that elevation of glial Ca2+ causes hyperactivation of calcineurin-dependent endocytosis and accumulation of early endosomes. Knockdown of sandman, a K2P channel, recapitulates NCKXzydeco seizures. In addition, restoring glial K+ buffering by ectopically expressing a leak K+ channel abolishes NCKXzydeco seizures. These data provide an unexpected link between glial Ca2+ signaling and the more well-known roles of glia in K+ buffering as a key mechanism for regulating neuronal excitability.
Critical Limb Ischemia Induces Remodeling of Skeletal Muscle Motor Unit and Myonuclear- and Mitochondrial-Domains
Authors: Mohiuddin Mahir , Lee Nan Hee , Moon June Young , Han Woojin M. , Anderson Shannon E. , Choi Jeongmoon J. , Nakhai Shadi , Tran Thu , Aliya Berna , Kim Do Young , Gerold Aimee , Hansen Laura , Taylor W. Robert , Jang Young C.
Published: September 2018

Critical limb ischemia, the most severe form of peripheral artery disease, leads to extensive damage and alterations in skeletal muscle homeostasis. Although recent developments towards revascularization therapies have been introduced, there has been limited research into treatments for ischemic myopathy. To elucidate the regenerative mechanism of the muscle stem cell and its niche components in response to ischemic insults, we explored interactions between the vasculature, motor neuron, muscle fiber, and the muscle stem cell. We first investigated changes in the neuromuscular junction and motor neuron innervation following a surgical hindlimb ischemia model of critical limb ischemia in mice. Along with previous findings that support remodeling of the neuromuscular junction, we report that ischemic injury also causes significant alterations to the myofiber through a muscle stem cell-mediated increase of myonuclei number per fiber, a concomitant decrease in myonuclear domain size, and an increase in relative mitochondrial content per myonucleus. These results indicate that as a regenerative response to critical limb ischemia, myofibers exhibit myonuclear expansion to allow enhanced transcriptional support and an increase in mitochondrial content for bioenergetic need of the energy-demanding tissue regeneration.
Asymmetric ephaptic inhibition between compartmentalized olfactory receptor neurons
Authors: Zhang Ye , Tsang Tin Ki , Bushong Eric A. , Chu Li-An , Chiang Ann-Shyn , Ellisman Mark H. , Reingruber Jürgen , Su Chih-Ying
Published: September 2018

In the Drosophila antenna, different subtypes of olfactory receptor neurons (ORNs) housed in the same sensory hair (sensillum) can inhibit each other non-synaptically. However, the mechanisms underlying this unusual form of lateral inhibition remain unclear. Here we use recordings from pairs of sensilla impaled by the same tungsten electrode to prove that direct electrical (“ephaptic”) interactions mediate lateral inhibition between ORNs. Intriguingly, within individual sensilla, we find that ephaptic lateral inhibition is asymmetric such that one ORN exerts greater influence onto its neighbor. Serial block-face scanning electron microscopy of genetically identified ORNs and circuit modeling indicate that asymmetric lateral inhibition reflects a surprisingly simple mechanism: the physically larger ORN in a pair corresponds to the dominant neuron in ephaptic interactions. Thus, morphometric differences between compartmentalized ORNs account for highly specialized inhibitory interactions that govern information processing at the earliest stages of olfactory coding.
Real-Time Observation of a Coherent Lattice Transformation into a High-Symmetry Phase
Authors: Teitelbaum Samuel W. , Shin Taeho , Wolfson Johanna W. , Cheng Yu-Hsiang , Molesky Ilana J. P. , Kandyla Maria , Nelson Keith A.
Published: September 2018

Excursions far from their equilibrium structures can bring crystalline solids through collective transformations including transitions into new phases that may be transient or long-lived. The direct spectroscopic observation of far-from-equilibrium rearrangements provides fundamental mechanistic insight into chemical and structural transformations and a potential route to practical applications, including ultrafast optical control over material structure and properties. However, in many cases, photoinduced transitions are irreversible or only slowly reversible, or the light fluence required exceeds material damage thresholds. This requirement precludes conventional ultrafast spectroscopy, in which optical excitation and probe pulses irradiate the sample many times, each measurement providing information about the sample response at just one probe delay time following excitation, with each measurement at a high repetition rate and with the sample fully recovering its initial state in between measurements. Using a single-shot, real-time measurement method, we are able to observe the photoinduced phase transition from the semimetallic, low-symmetry phase of crystalline bismuth into a high-symmetry phase whose existence at high electronic excitation densities is predicted based on earlier measurements at moderate excitation densities below the damage threshold. Our observations indicate that coherent lattice vibrational motion launched upon photoexcitation with an incident fluence above 10  mJ/cm2 in bulk bismuth brings the lattice structure directly into the high-symmetry configuration for several picoseconds, after which carrier relaxation and diffusion restore the equilibrium lattice configuration.

Published by the American Physical Society
2018
The effect of executive incentives on FDI ambidexterity
Authors: Li Zijie , Gao Qiuling , Shen Kai , Zhang Junyue
Published: September 2018

Purpose

This paper aims to examine different hypotheses concerning the effects of executive incentive on the degree of Chinese foreign direct investment (FDI) ambidexterity. Specifically, this study provides new insights on how executive equity incentive and executive control right incentive may affect overseas ambidextrous strategy of Chinese enterprises.

Design/methodology/approach

This study used panel data of Chinese manufacturing listed companies in 2006-2015 to explore the relationships between related factors. Hypotheses are tested by using regression analysis.

Findings

This study found that executive equity incentive is positively related to the degree of FDI ambidexterity. It also found that the level at which control right incentives of executive are made has a curvilinear relationship with degree of FDI ambidexterity. Higher level of control right incentive of executive will be associated with higher degree of FDI ambidexterity; however, beyond some level, higher control right incentive of executive will be associated with lower degree of FDI ambidexterity.

Research limitations/implications

This paper has implications to future research and companies’ everyday practice on ambidextrous FDI strategy.

Originality/value

Based on the principal-agent framework and incentive theory, this paper offers an interesting insight of achieving balance of ambidextrous strategy for Chinese multinational enterprises by involving the different roles of executive equity incentive and executive control right incentive they played.
A stability controlling-based approach for designing 1-D variable fractional delay all-pass filters
Authors: Zhao Hui , Li Shengnan , Yang Hongyu , Zhou Quan
Published: September 2018

Purpose

Variable fractional delay filtering is an important technology in signal processing; the research shows that all-pass variable fractional delay (VFD) filters achieve higher design accuracy than FIR VFD filters; therefore, the design, analysis and implementation of all-pass VFD filters are of great importance.

Design/methodology/approach

In this paper, a two-stage approach for the design of general 1-D stable VFD all-pass filters is proposed. The method takes the desired group delay range [N−1, N], where N is the filter order.

Findings

The design algorithm is decomposed into two design stages: first, a set of fixed delay all-pass filters are designed by minimizing a set of objective functions defined in terms of approximating error criterion and filter stability constraint. Then, the design result is determined by fitting each of the fixed delay all-pass filter coefficients as 1-D polynomials. A design example together with its comparisons with those of the recent literature studies is given to justify the effectiveness of the proposed design method.

Originality/value

An illustrating design example shows that the method proposed can achieve better filter performances than the existing ones.
Topology optimisation using nonlinear behaviour of ferromagnetic materials
Authors: Mohamodhosen Bilquis Bibi Safoorah , Gillon Frederic , Tounzi Mounaim , Chevallier Loïc
Published: September 2018

Purpose

The purpose of this paper is to propose a methodology to seek the optimal topology of electromagnetic devices using the density method while taking into account the non-linear behaviour of ferromagnetic materials. The tools and methods used are detailed and applied to a three-dimensional (3D) electromagnet for analysis and validation. Resulting topologies with and without the non-linear behaviour are investigated.

Design/methodology/approach

The polynomial mapping is used with the density method for material distribution in the optimisation domain. To consider the non-linear behaviour of the materials, an analytical approximation based on the Marrocco equation is used and combined with the polynomial mapping to solve the problem. Furthermore, to prevent the occurrence of intermediate materials, a weighted sum of objectives is used in the optimisation problem to eliminate these undesired materials.

Findings

Taking into account the non-linear materials behaviour and 3D model during topology optimisation (TO) is important, as it produces more physically feasible and coherent results. Moreover, the use of a weighted sum of objectives to eliminate intermediate materials increases the number of evaluations to reach the final solution, but it is efficient.

Practical implications

Considering non-linear materials behaviour yields results closer to reality, and physical feasibility of structures is more obvious in absence of intermediate materials.

Originality/value

This work tackles an obstacle of TO in electromagnetism which is often overlooked in literature, that is, non-linear behaviour of ferromagnetic materials by proposing a methodology.
Building maintenance management activities in a public institution
Authors: Alves Tenório de Morais Gabriela , Casado Lordsleem Júnior Alberto
Published: September 2018

Purpose

The purpose of this paper is to present a case study about the diagnosis perform of the building maintenance process in a Brazilian Government public institution.

Design/methodology/approach

The research methodology involved interviews, maintenance process diagnosis and request database analysis.

Findings

The results showed that the average attendance rate of the received requests is 86 percent and the greatest demands are related to the refrigeration, electrical and hydrosanitary installations, which represent 55 percent of the total requests. According to maintenance management, it was verified the need for a better structuring of the requests receiving system and greater rigor to the services quality.

Originality/value

The paper extends the knowledge relating to the building maintenance process in government public institutions. The government building maintenance management characterization can serve as reference and benchmark for similar institutions.