bluuebunny/crossref_metadata_2025 huggingface dataset:
Fetoscopic two‐layer closure of open neural tube defects
Authors: Giné C. , Arévalo S. , Maíz N. , Rodó C. , Manrique S. , Poca A. , Molino J. A. , Carreras E. , López M.
Published: June 2018

Objective

Fetoscopy for closure of open neural tube defects (NTD) remains controversial, as the use of patches or single‐layer closure is not considered to meet the standards of good neurosurgical reconstruction. In this study, we describe a fetoscopic two‐layer (myofascial and skin) closure technique for the treatment of NTD in five patients and report the preliminary anatomical outcome at birth.

Methods

From February to September 2017, five pregnant women with a fetus with a NTD, including three cases of myelomeningocele and two cases of myelocele, were operated on using a fetoscopic two‐layer closure technique. In this technique, with the uterus exteriorized and using three 10‐Fr ports, the placode is dissected from the surrounding tissue and detethered, removing the cystic tissue. The skin is undermined by blunt dissection and the defect is sutured to the midline in two layers (myofascial and skin) using a running 4/0 resorbable barbed suture.

Results

Median gestational age at the procedure was 24 + 3 (range, 23 + 5 to 27 + 3) weeks. Surgery was successful in all cases, without any intraoperative complications. Median time in surgery was 180 (range, 140–180) min and median time for fetoscopy was 105 (range, 65–120) min. In terms of obstetric complications, three cases of premature rupture of membranes and one case of chorioamnionitis were recorded. Median gestational age at delivery was 34 + 1 (range, 25 + 4 to 37 + 2) weeks and two patients delivered vaginally. The closed defect was watertight with good quality tissue in all cases.

Conclusion

Fetoscopic two‐layer closure of NTD may improve the quality of the tissue covering the defect, diminishing the need for postnatal surgical revision, and preserving the well‐documented beneficial effects of prenatal closure on the neural tissue and hindbrain herniation. However, this technique may not be appropriate for those cases with wide diastasis of the myofascial layer or with a low quantity of available tissue. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.
Latitude and elevation as factors controlling occurrence of calanoid copepods in marginal lotic waters in New South Wales, Australia
Authors: Kobayashi Tsuyoshi , Miller Jan , Bayly Ian A. E. , Tang Cheryl , Hunter Simon J. , Ralph Timothy J. , Stone Luke
Published: June 2018

Freshwater calanoid copepods develop abundant populations in lentic water bodies such as lakes, reservoirs and lagoons. In this study, we examined the potential habitat value of edges in lotic systems such as creeks and rivers where waters tend to stagnate, providing lentic‐like environments. We examined a total of 353 edge samples collected from 321 sites across the state of New South Wales, Australia, with latitudes in the range 28.3–37.4°S and elevations in the range 2–1834 m above sea level. Of the total samples examined, calanoid copepods were found in 94 samples, with the frequency of occurrences of species decreasing in the order:Boeckella fluvialisHenry,B. triarticulata(Thomson),Gladioferens spinosusHenry,G. pectinatus(Brady),B. majorSearle,B. minutaSars, andCalamoecia lucasiBrady. The probability of occurrence of the calanoid copepods was related negatively to both latitude (as absolute values) and elevation, based on logistic regression models. We conclude that the edges of many lotic systems provide additional habitats for some species of freshwater calanoid copepods, with constraints on their distributions along latitudinal and elevational gradients.
Differences in Coracoid and Glenoid Dimensions Based on Sex, Race, and Age: Implications for Use of the Latarjet Technique in Glenoid Reconstruction
Authors: Knapik Derrick M. , Cumsky Jameson , Tanenbaum Joseph E. , Voos James E. , Gillespie Robert J.
Published: June 2018

Background

The Latarjet procedure restores shoulder stability through reconstruction of the glenoid arc. Prior investigations of glenoid and coracoid dimensions have been underpowered to detect differences based on sex and race.

Questions/Purposes

We sought to establish normative values for glenoid width and coracoid dimensions based on sex, race, and age. In addition, we assessed the restoration of glenoid dimensions using the classic and modified Latarjet techniques (classic technique: placing lateral surface of the coracoid to the glenoid; modified technique: placing inferior surface of the coracoid to the glenoid).

Methods

A total of 993 cadaveric specimens ( n = 1986 scapulae) from people over 18 years of age at the time of death were analyzed. Measurements of maximal glenoid width, coracoid width, thickness, and length were recorded. Statistical analysis was performed to detect differences based on sex and race, while univariable linear regression was used to determine the association of increasing age on measured dimensions.

Results

All dimensions of specimens were significantly larger in males than in females. Caucasians possessed larger mean glenoid width, coracoid width, and coracoid length, while coracoid thickness was significantly larger in African Americans. Linear regression analysis found that increasing age was associated with increased glenoid width and coracoid dimensions. Coracoid positioning restored glenoid width in defects measuring 20% of glenoid width using both classic and modified Latarjet techniques, while defects measuring up to 25% were more accurately reproduced using the modified technique.

Conclusion

Dimensions were significantly larger in males and in Caucasians, aside from coracoid thickness. Mean dimensions increased with advancing age. Coracoid positioning using classic or modified Latarjet techniques restored glenoid width defects measuring 20% of the glenoid width, while the modified technique allowed for restoration of larger defects.
Partners’ Educational Pairings and Fertility Across Europe
Authors: Nitsche Natalie , Matysiak Anna , Van Bavel Jan , Vignoli Daniele
Published: June 2018

We provide new evidence on the education-fertility relationship by using EU-SILC panel data on 24 European countries to investigate how couples’ educational pairings predict their childbearing behavior. We focus on differences in first-, second-, and third-birth rates among couples with varying combinations of partners’ education. Our results show important differences in how education relates to parity progressions depending on the education of the partner. First, highly educated homogamous couples show a distinct childbearing behavior in most country clusters. They tend to postpone the first birth most and display the highest second- and third-birth rates. Second, contrary to what may be expected based on the “new home economics” approach, hypergamous couples with a highly educated male and a lower-educated female partner display among the lowest second-birth transitions. Our findings underscore the relevance of interacting both partners’ education for a better understanding of the education-fertility relationship.
Strain Cervical Elastography in Pregnancy: Feasibility Study and Its Usefulness in Prediction of Preterm Birth
Authors: Shah Nupur , Kaul Anita
Published: June 2018

Cervix in pregnancy is a biomechanical barrier holding the uterine contents till the time of parturition. The feasibility and reproducibility of assessing cervical tissue stiffness for predicting preterm birth by a standard method using strain cervical elastography were studied here. The prospective study included use of transvaginal strain elastography assessment of cervix at 22–24 weeks in three regions of interest: (1) Endocervical canal and entire cervix in mid-sagittal plane (2) At the level of external os in cross section and (3) at the level of internal os in cross-sectional plane, with constant pressure application each time. Strain ratios were recorded twice for the operator 1 and once by operator 2. Cervical length was also measured according to standard protocol. The measurement of strain ratios was possible in all the 85 included cases. Intra or and inter operator agreement was good for all the 3 ROIs by Kappa analysis and Pearson coefficient. In 10 cases of preterm birth with cervical length ≤≤25 mm, the strain ratios at internal os were observed to be <≤1. Strain cervical elastography in pregnancy appears to be a novel, feasible and reproducible technique using a standard method for prediction of preterm birth.
Radiocarbon chronology of occupation of the site Chicha and Bayesian statistics for the assessment of a discontinuous transition from Late Bronze to Early Iron Age (West Siberia)
Authors: J. Schneeweiss , Becker F. , Molodin V.I. , Parzinger H. , Marchenko Zh.V. , Svyatko S.V.
Published: June 2018

The Late Bronze to Iron Age transition in West Siberia involved significant cultural and political changes, which were reflected in the emergence of protourban settlements in the forest–steppe zone. The transition is roughly dated to the turn from the 2nd to the 1st mil. BC, mainly based on archaeological artefacts and on the general sociocultural development. A more precise radiocarbon dating for this transition was problematic mainly because of the general lack of data for West Siberia. This paper analyzes the chronology of the Late Bronze to Iron Age transition at Chicha, a reference site in the region for this period. The assessment of a possible hiatus between the Late Bronze Age and the following transitional period at Chicha is the key issue of our paper, as its presence may have far reaching cultural implications. To increase the precision of the radiocarbon chronology with focus on the possible hiatus, the samples from well-defined stratigraphic contexts were analyzed using Bayesian modeling incorporating stratigraphic information. The performed chronological modeling supports existing archaeological hypothesis of a hiatus at the very end of the 2nd mil. BC, just before the regular emergence of a new protourban settlement at the site of an abandoned Late Bronze settlement. A sensitivity analysis including the simulated hiatus confirms the reliability of the model. A complete population change seems to be plausible. The protourban settlement of Chicha, typical of the Transitional period, did not exist very long. With the emergence of the early nomadic cultures in the South Siberian steppes at the beginning of the 1st mil. BC, it most probably stopped functioning. The cultural development of that time, former believed to be continuous, was deeply interrupted several times.
Magnetic viscosity effect on TEM data of an array with a fixed transmitter loop
Authors: Kozhevnikov N.O. , Antonov E.Yu.
Published: June 2018

In this paper, we present and discuss the results of modeling of the transient induction processes observed at different distances from the center of a transmitter loop in studies of a two-layer earth in which the magnetic susceptibility of the top layer or the base depends on frequency. Profiling graphs (the offset is plotted on the abscissa, and the EMF induced in the receiver coil at a fixed time is plotted on the ordinate) show that the polarity of the EMF changes as the offset increases. For the model with a magnetic layer of any thickness, the polarity of the EMF reverses immediately after the receiver crosses the loop wire. For the model with a magnetic base, the offset at which the EMF polarity reversal occurs is the larger the greater the thickness of the layer. For both models, the EMF at a fixed time depends on the thickness of the layer and the offset. Particularly strong dependence of the EMF on layer thickness or offset is observed near the loop side. Therefore, measurements near the wire make it possible to determine the thickness of the layer in the case where it is much less than the length of the loop side. The overall effect of magnetic relaxation and transient eddy currents leads to the fact that small changes in the layer thickness or offset can lead to a dramatic change in the transient response.
Association between ondansetron use and symptom persistence in children with concussions: A 5P substudy
Authors: Gravel Jocelyn , Boutis Kathy , Tang Ken , Beauchamp Miriam H. , Freedman Stephen B. , Dubrovsky Alexander Sasha , Gagnon Isabelle , Momoli Frank , Zemek Roger
Published: June 2018

Objective

Ondansetron is increasingly administered to children suffering from concussion-associated nausea/vomiting. We examined the association between ondansetron administration and post-concussion symptoms in children at 1 week and 1 month following the concussion.

Methods

This was a secondary analysis of data collected prospectively in a cohort study conducted in nine pediatric emergency departments (EDs) (5P study). Participants were children ages between 5 and 17.99 years who sustained a concussion in the previous 48 hours. For the current study, only 5P participants who reported nausea and/or vomiting in the ED were eligible. The exposure of interest was ondansetron administration; the comparison group included all other participants. The primary outcome was an increase in at least three symptoms of the Post-Concussion Symptom Inventory score at 1 week and 1 month following trauma.

Results

Among the 3,063 children included in the 5P study, 1805 (59%) reported nausea and provided data at 1 week and/or 1 month. Among them, 132 (7%) received ondansetron. Multivariable logistic regression adjusted for confounders did not show an association between ondansetron use and the risk of persistent post-concussion symptoms at 1 week (OR: 1.13 [95% CI: 0.86-1.49]), but it was associated with a higher risk at 1 month (OR: 1.33 [95% CI: 1.05-1.97]).

Conclusion

In children presenting to the ED with an acute concussion, ondansetron use was associated with a higher risk of persistent post-concussion symptoms at 1 month. Although this may be related to the limitations of the design, it highlights the importance of evaluating this association using a randomized clinical trial.
The Duty to Investigate Violations of the Right to Life in Armed Conflicts in the Jurisprudence of the Inter-American Court of Human Rights
Authors: Frisso Giovanna Maria
Published: June 2018

This article explores how the Inter-American Court of Human Rights (the Court) has dealt with allegations of violations of the right to life during an armed conflict and, in particular, how it has dealt with allegations of violation of the obligation to investigate such allegations. The article notes that international humanitarian law (IHL) was initially used by the Court to strengthen the general obligations of states to protect the rights guaranteed by the American Convention on Human Rights (ACHR). Later IHL began informing the interpretation of specific rights. This change has been more significant in relation to the interpretation of the right to life under the ACHR than in the examination of state compliance with the right of access to justice, which encompasses the duty to investigate allegations of violations of the right to life during an armed conflict. The analysis of the Court's jurisprudence demonstrates that the different ways in which the Court has addressed the relationship between IHL and international human rights law (IHRL) have been informed by its primary effort to ensure that the interpretation of the ACHR provides the widest protection possible to individual rights.
NGO Fact-Finding for IHL Enforcement: In Search of a New Model
Authors: Steinberg Gerald M , Herzberg Anne
Published: June 2018

Human Rights Watch (HRW), Amnesty International (Amnesty), and other like-minded organisations have become major actors in the world of international humanitarian law (IHL). Every year they issue hundreds of publications purporting to document violations and to promote IHL enforcement. These publications are ubiquitously cited in the media, and used as source material for governmental and United Nations inquiries, quasi-judicial bodies, the International Criminal Court, academic studies, and other frameworks. Yet, despite the increase in the number, role and influence of non-governmental organisations (NGOs) working on IHL enforcement, conflicts and civilian deaths show no signs of abating. Among the factors that reduce NGO impact in these areas is the demonstrated weakness of these organisations in the realm of fact-finding, and the tension between these activities and emphasis on political advocacy. This article will thus analyse both objective and subjective aspects of NGO fact-finding during armed conflict, including mandates and methodology, selectivity, the application of legal standards, military expertise and sourcing. These issues will be examined through case studies of Amnesty and HRW publications on the conflicts in Yemen, Ukraine and the 2014 Gaza War. The article will conclude with recommendations for NGOs and the actors with which they interact.
Solid and fluid segments within the same molecule of stratum corneum ceramide lipid
Authors: Pham Quoc Dat , Mojumdar Enamul H. , Gooris Gert S. , Bouwstra Joke A. , Sparr Emma , Topgaard Daniel
Published: June 2018

The outer layer of the skin, stratum corneum (SC) is an efficient transport barrier and it tolerates mechanical deformation. At physiological conditions, the majority of SC lipids are solid, while the presence of a small amount of fluid lipids is considered crucial for SC barrier and material properties. Here we use solid-state and diffusion nuclear magnetic resonance to characterize the composition and molecular dynamics of the fluid lipid fraction in SC model lipids, focusing on the role of the essential SC lipid CER EOS, which is a ceramide esterified omega-hydroxy sphingosine linoleate with very long chain. We show that both rigid and mobile structures are present within the same CER EOS molecule, and that the linoleate segments undergo fast isotropic reorientation while exhibiting extraordinarily slow self-diffusion. The characterization of this unusual self-assembly in SC lipids provides deepened insight into the molecular arrangement in the SC extracellular lipid matrix and the role of CER EOS linoleate in the healthy and diseased skin.
BANK RUNS: THE PREDEPOSIT GAME
Authors: Shell Karl , Zhang Yu
Published: June 2018

We analyze in some detail the full predeposit game in a simple, tractable, yet very rich, banking environment. How does run-risk affect the optimal deposit contract? If there is a run equilibrium in the postdeposit game, then the optimal contract in the predeposit game tolerates small-probability runs. However, this does not mean that small changes in run-risk are ignored. In some cases, the optimal contract becomes—as one would expect—strictly more conservative as the run-probability increases (until it switches to the best run-proof contract), and the equilibrium allocation is not a mere randomization over the equilibrium allocations from the postdeposit game. In other cases, the allocation is a mere randomization over the equilibria from the postdeposit game. In the first cases (the more intuitive cases), the incentive constraint does not bind. In the second cases, the incentive constraint does bind.
Effectiveness of zinc-fortified water on zinc intake, status and morbidity in Kenyan pre-school children: a randomised controlled trial
Authors: Kujinga Prosper , Galetti Valeria , Onyango Elizabeth , Jakab Viktor , Buerkli Simone , Andang’o Pauline , Brouwer Inge D , Zimmermann Michael B , Moretti Diego
Published: June 2018

Objective

Zn deficiency and diarrhoea are prevalent and may coexist in children living in low-resource settings. Recently, a novel approach for delivering Zn via microbiologically treated, Zn-fortified water was shown to be effective in improving Zn status in West African schoolchildren. We assessed the effectiveness of Zn-fortified, microbiologically purified water delivered as a household intervention on Zn intake, status and morbidity in children aged 2–6 years from rural western Kenya.

Design

Randomised controlled trial. Intervention included households assigned to water treatment device with (ZFW) or without (FW) Zn delivery capability

Setting

Rural households in Kisumu, western Kenya.

Subjects

Children aged 2–6 years.

Results

The ZFW group had higher dietary Zn intake compared with the FW group. ZFW contributed 36 and 31 % of daily requirements for absorbable Zn in children aged 2–3 and 4–6 years, respectively, in the ZFW group. Consumption of Zn-fortified water resulted in lower prevalence of reported illness (risk ratio; 95 % CI) in the ZFW group compared with the FW group: for cold with runny nose (0·91; 0·83, 0·99; P=0·034) and abdominal pain (0·70; 0·56, 0·89; P=0·003) in the intention-to-treat analysis and for diarrhoea (0·72; 0·53, 0·96; P=0·025) in the per-protocol analysis. We did not detect an effect of treatment on plasma Zn concentration.

Conclusions

Daily consumption of Zn-fortified, microbiologically treated water results in increased intake of absorbable dietary Zn and may help in preventing childhood infections in pre-school children in rural Africa.
TEMPORAL AND SPATIAL HETEROGENEITY IN PULMONARY PERFUSION: A MATHEMATICAL MODEL TO PREDICT INTERACTIONS BETWEEN MACRO- AND MICRO-VESSELS IN HEALTH AND DISEASE
Authors: CLARK A. R. , TAWHAI M. H.
Published: June 2018

Heterogeneity in pulmonary microvascular blood flow (perfusion) provides an early indicator of lung disease or disease susceptibility. However, most computational models of the pulmonary vasculature neglect structural heterogeneities, and are thus not accurate predictors of lung function in disease that is not diffuse (spread evenly through the lung). Models that do incorporate structural heterogeneity have either neglected the temporal dynamics of blood flow, or the structure of the smallest blood vessels. Larger than normal oscillations in pulmonary capillary calibre, high oscillatory stress contribute to disease progression. Hence, a model that captures both spatial and temporal heterogeneity in pulmonary perfusion could provide new insights into the early stages of pulmonary vascular disease. Here, we present a model of the pulmonary vasculature, which captures both flow dynamics, and the anatomic structure of the pulmonary blood vessels from the right to left heart including the micro-vasculature. The model is compared to experimental data in normal lungs. We confirm that spatial heterogeneity in pulmonary perfusion is time-dependent, and predict key features of pulmonary hypertensive disease using a simple implementation of increased vascular stiffness.
Influence of Soil Moisture on Absorption, Translocation, and Metabolism of Florpyrauxifen-benzyl
Authors: Miller M. Ryan , Norsworthy Jason K.
Published: June 2018

Florpyrauxifen-benzyl is a new active ingredient that represents an additional tool in rice (Oryza sativaL.) weed control by providing an alternative mechanism of action. Studies were conducted to evaluate soil moisture influences on florpyrauxifen-benzyl absorption, translocation, and metabolism in three problematic weeds. In the absorption/translocation study, barnyardgrass [Echinochloa crus-galli(L.) P. Beauv.], hemp sesbania [Sesbania herbacea(Mill.) McVaugh], and yellow nutsedge (Cyperus esculentusL.) were treated with [14C]florpyrauxifen-benzyl under two soil moisture regimes (7.5% and 60% field capacity). Greater absorption occurred under moist conditions (60% soil moisture content). More translocation of the herbicide to the area above the treated leaf occurred under moist versus dry soil across all weed species.Sesbania herbaceatranslocated 25% of the absorbed herbicide above the treated leaf, a result greater than that of the other two weed species at 60% soil moisture. However, no differences in translocation occurred among the weed species at the 7.5% soil moisture regime. In the metabolism study, 95% of the herbicide recovered was in its acid form under the high soil moisture regime forS. herbacea, a species that shows extreme sensitivity to even low doses of this herbicide, and soil moisture influenced the amount of acid form found in all species. While these data provide a limited view into the physiological processes being affected, they do suggest that forE. crus-galli,S. herbacea, andC. esculentus, soil moisture content in the field will likely play a significant role in absorption, translocation, and metabolism of florpyrauxifen-benzyl.
Floe Size Effect on Wave‐Ice Interactions: Possible Effects, Implementation in Wave Model, and Evaluation
Authors: Boutin Guillaume , Ardhuin Fabrice , Dumont Dany , Sévigny Caroline , Girard‐Ardhuin Fanny , Accensi Mickael
Published: June 2018

Wind waves may play an important role in the evolution of sea ice. That role is largely determined by how fast the ice layer dissipates the wave energy. The transition from a continuous layer of ice to a series of broken floes is expected to have a strong impact on the several attenuation processes. Here we explore the possible effects of basal friction, scattering, and dissipation within the ice layer. The ice is treated as a single layer that can be fractured in many floes. Dissipation associated with ice flexure is evaluated using an anelastic linear dissipation and a cubic inelastic viscous dissipation. Tests aiming to reproduce a Marginal Ice Zone are used to discuss the effects of each process separately. Attenuation is exponential for friction and scattering. Scattering produces an increase in the wave height near the ice edge and broadens the wave directional spectrum, especially for short‐period waves. The nonlinear inelastic dissipation is larger for larger wave heights as long as the ice is not broken. These effects are combined in a realistic simulation of an ice break‐up event observed south of Svalbard in 2010. The recorded rapid shift from a strong attenuation to little attenuation when the ice is broken is only reproduced when using a nonlinear dissipation that vanishes when the ice is broken. A preliminary pan‐Arctic test of these different parameterizations suggests that inelastic dissipation alone is not enough and requires its combination with basal friction.
Subpolar North Atlantic Overturning and Gyre‐Scale Circulation in the Summers of 2014 and 2016
Authors: Holliday N. P. , Bacon S. , Cunningham S. A. , Gary S. F. , Karstensen J. , King B. A. , Li F. , Mcdonagh E. L.
Published: June 2018

The Atlantic Meridional Overturning Circulation (AMOC) is a key component of the global climate system through its transport of heat and freshwater. The subpolar North Atlantic (SPNA) is a region where the AMOC is actively developed and shaped though mixing and water mass transformation and where large amounts of heat are released to the atmosphere. Two hydrographic transbasin sections in the summers of 2014 and 2016 provide highly spatially resolved views of the SPNA velocity and property fields on a line from Canada to Greenland to Scotland. Estimates of the AMOC, isopycnal (gyre‐scale) transport, and heat and freshwater transport are derived from the observations. The overturning circulation, the maximum in northward transport integrated from the surface to seafloor and computed in density space, has a high range, with 20.6 ± 4.7 Sv in June–July 2014 and 10.6 ± 4.3 Sv in May–August 2016. In contrast, the isopycnal (gyre‐scale) circulation was lowest in summer 2014: 41.3 ± 8.2 Sv compared to 58.6 ± 7.4 Sv in 2016. The heat transport (0.39 ± 0.08 PW in summer 2014, positive is northward) was highest for the section with the highest AMOC, and the freshwater transport was largest in summer 2016 when the isopycnal circulation was high (−0.25 ± 0.08 Sv). Up to 65% of the heat and freshwater transport was carried by the isopycnal circulation, with isopycnal property transport highest in the western Labrador Sea and the eastern basins (Iceland Basin to Scotland).
A gene transfer event suggests a long-term partnership between eustigmatophyte algae and a novel lineage of endosymbiotic bacteria
Authors: Yurchenko Tatiana , Ševčíková Tereza , Přibyl Pavel , El Karkouri Khalid , Klimeš Vladimír , Amaral Raquel , Zbránková Veronika , Kim Eunsoo , Raoult Didier , Santos Lilia M A , Eliáš Marek
Published: June 2018

Rickettsiales are obligate intracellular bacteria originally found in metazoans, but more recently recognized as widespread endosymbionts of various protists. One genus was detected also in several green algae, but reports on rickettsialean endosymbionts in other algal groups are lacking. Here we show that several distantly related eustigmatophytes (coccoid algae belonging to Ochrophyta, Stramenopiles) are infected by Candidatus Phycorickettsia gen. nov., a new member of the family Rickettsiaceae. The genome sequence of Ca. Phycorickettsia trachydisci sp. nov., an endosymbiont of Trachydiscus minutus CCALA 838, revealed genomic features (size, GC content, number of genes) typical for other Rickettsiales, but some unusual aspects of the gene content were noted. Specifically, Phycorickettsia lacks genes for several components of the respiration chain, haem biosynthesis pathway, or c-di-GMP-based signalling. On the other hand, it uniquely harbours a six-gene operon of enigmatic function that we recently reported from plastid genomes of two distantly related eustigmatophytes and from various non-rickettsialean bacteria. Strikingly, the eustigmatophyte operon is closely related to the one from Phycorickettsia, suggesting a gene transfer event between the endosymbiont and host lineages in early eustigmatophyte evolution. We hypothesize an important role of the operon in the physiology of Phycorickettsia infection and a long-term eustigmatophyte-Phycorickettsia coexistence.
Pharmacological inactivation of the PI3K p110δ prevents breast tumour progression by targeting cancer cells and macrophages
Authors: Goulielmaki Evangelia , Bermudez-Brito Miriam , Andreou Margarita , Tzenaki Niki , Tzardi Maria , de Bree Eelco , Tsentelierou Eleftheria , Makrigiannakis Antonis , Papakonstanti Evangelia A.
Published: June 2018

Patient selection for PI3K-targeted solid cancer treatment was based on the PIK3CA/PTEN mutational status. However, it is increasingly clear that this is not a good predictor of the response of breast cancer cells to the anti-proliferative effect of PI3K inhibitors, indicating that isoform(s) other than p110α may modulate cancer cells sensitivity to PI3K inhibition. Surprisingly, we found that although no mutations in the p110δ subunit have been detected thus far in breast cancer, the expression of p110δ becomes gradually elevated during human breast cancer progression from grade I to grade III. Moreover, pharmacological inactivation of p110δ in mice abrogated the formation of tumours and the recruitment of macrophages to tumour sites and strongly affected the survival, proliferation and apoptosis of grafted tumour cells. Pharmacological inactivation of p110δ in mice with defective macrophages or in mice with normal macrophages but grafted with p110δ-lacking tumours suppressed only partly tumour growth, indicating a requisite role of p110δ in both macrophages and cancer cells in tumour progression. Adoptive transfer of δD910A/D910A macrophages into mice with defected macrophages suppressed tumour growth, eliminated the recruitment of macrophages to tumour sites and prevented metastasis compared with mice that received WT macrophages further establishing that inactivation of p110δ in macrophage prevents tumour progression. Our work provides the first in vivo evidence for a critical role of p110δ in cancer cells and macrophages during solid tumour growth and may pave the way for the use of p110δ inhibitors in breast cancer treatment.
The transcription factor Zfp90 regulates the self-renewal and differentiation of hematopoietic stem cells
Authors: Liu Ting , Kong Wei-xia , Tang Xiao-yi , Xu Man , Wang Qing-han , Zhang Bin , Hu Liang-ding , Chen Hu
Published: June 2018

Hematopoietic stem cells (HSCs) can give rise to all blood cells that are essential to defend against pathogen invasion. The defective capability of HSC self-renewal is linked to many serious diseases, such as anemia. However, the potential mechanism regulating HSC self-renewal has not been thoroughly elucidated to date. In this study, we showed that Zfp90 was highly expressed in HSCs. Zfp90 deficiency in the hematopoietic system caused impaired HSPC pools and led to HSC dysfunction. We showed that Zfp90 deletion inhibited HSC proliferation, while HSC apoptosis was not affected. Regarding the mechanism of this effect on HSC proliferation, we found that Zfp90 interacted with Snf2l, a subunit of the NURF complex, to regulate Hoxa9 expression. Ectopic expression of Hoxa9 rescued the HSC repopulation capacity in Zfp90-deficient mice, which indicates that Hoxa9 is the downstream effector of Zfp90. In summary, our findings identify Zfp90 as a key transcription factor in determining the fate of HSCs.
Molecular characterization and integrative genomic analysis of a panel of newly established penile cancer cell lines
Authors: Zhou Qiang-hua , Deng Chuang-zhong , Li Zai-shang , Chen Jie-ping , Yao Kai , Huang Kang-bo , Liu Ting-yu , Liu Zhuo-wei , Qin Zi-ke , Zhou Fang-jian , Huang Wenlin , Han Hui , Liu Ran-yi
Published: June 2018

Cell line models are essential tools to study the molecular mechanisms underlying tumor initiation and progression. There are limited treatment options for penile squamous cell carcinoma (PSCC), accounting for 1–2% of male tumors in developing countries, and limited progress in preclinical research in PSCC due to lacking available models with identified genomic characteristics. Here, biological and molecular characteristics and whole-genomic alterations were analyzed in a panel of PSCC cell lines newly established in our laboratory. These cell lines were all human papillomavirus (HPV)-negative, epithelial-like, immortalized, and tumorigenic in nude mice, whereas they displayed different proliferation, migration and invasion capacities in vitro, and tumorigenic ability in nude mice. They were all cisplatin sensitive, anti-EGFR therapy resistant, and androgen irresponsive. Whole-genomic sequecing analysis revealed that transition mutations (C:G>T:A and T:A>C:G) were the most common substitution types in these cell lines, whereas ERCC5, TP53, PTH1, CLTCL1, NOTCH2, MAP2K3, CDK11A/B, USP6, ADCH5, BCLAF1, CDKN2A, FANCD2, HRAS, and NOTCH1 were the most frequently altered genes. Amplifications of MYC, PLAG1, NCOA2, RUNX1T1, COX6C, and EGFR and losses of FBXW7, TET2, XPC, and FANCE were frequently observed in cell lines. The exomic variations between cell lines and their corresponding cancer tissues were highly consistent. Genetic variations were mainly involved in the MAPK, Jak-STAT, TGF-beta, Notch, and apoptosis signaling pathways. Conclusively, these panel of PSCC cell lines established in our laboratory harbor some common or specific biological characteristics and genomic variations, and they may serve as optimal models to investigate the molecular mechanisms underlying the progression, metastasis, relapses, and treatment resistance of PSCC and to develop effective treatment strategy.
Inflammation, neurodegeneration and protein aggregation in the retina as ocular biomarkers for Alzheimer’s disease in the 3xTg-AD mouse model
Authors: Grimaldi Alfonso , Brighi Carlo , Peruzzi Giovanna , Ragozzino Davide , Bonanni Valentina , Limatola Cristina , Ruocco Giancarlo , Di Angelantonio Silvia
Published: June 2018

Alzheimer's disease (AD) is the most common cause of dementia in the elderly. In the pathogenesis of AD a pivotal role is played by two neurotoxic proteins that aggregate and accumulate in the central nervous system: amyloid beta and hyper-phosphorylated tau. Accumulation of extracellular amyloid beta plaques and intracellular hyper-phosphorylated tau tangles, and consequent neuronal loss begins 10–15 years before any cognitive impairment. In addition to cognitive and behavioral deficits, sensorial abnormalities have been described in AD patients and in some AD transgenic mouse models. Retina can be considered a simple model of the brain, as some pathological changes and therapeutic strategies from the brain may be observed or applicable to the retina. Here we propose new retinal biomarkers that could anticipate the AD diagnosis and help the beginning and the follow-up of possible future treatments. We analyzed retinal tissue of triple-transgenic AD mouse model (3xTg-AD) for the presence of pathological hallmarks during disease progression. We found the presence of amyloid beta plaques, tau tangles, neurodegeneration, and astrogliosis in the retinal ganglion cell layer of 3xTg-AD mice, already at pre-symptomatic stage. Moreover, retinal microglia in pre-symptomatic mice showed a ramified, anti-inflammatory phenotype which, during disease progression, switches to a pro-inflammatory, less ramified one, becoming neurotoxic. We hypothesize retina as a window through which monitor AD-related neurodegeneration process.
Deducing the presence of proteins and proteoforms in quantitative proteomics
Authors: Bamberger Casimir , Martínez-Bartolomé Salvador , Montgomery Miranda , Pankow Sandra , Hulleman John D. , Kelly Jeffery W. , Yates John R.
Published: June 2018

The human genome harbors just 20,000 genes suggesting that the variety of possible protein products per gene plays a significant role in generating functional diversity. In bottom-up proteomics peptides are mapped back to proteins and proteoforms to describe a proteome; however, accurate quantitation of proteoforms is challenging due to incomplete protein sequence coverage and mapping ambiguities. Here, we demonstrate that a new software tool called ProteinClusterQuant (PCQ) can be used to deduce the presence of proteoforms that would have otherwise been missed, as exemplified in a proteomic comparison of two fly species, Drosophilamelanogaster and D. virilis. PCQ was used to identify reduced levels of serine/threonine protein kinases PKN1 and PKN4 in CFBE41o− cells compared to HBE41o− cells and to elucidate that shorter proteoforms of full-length caspase-4 and ephrin B receptor are differentially expressed. Thus, PCQ extends current analyses in quantitative proteomics and facilitates finding differentially regulated proteins and proteoforms.
High energy-density and reversibility of iron fluoride cathode enabled via an intercalation-extrusion reaction
Authors: Fan Xiulin , Hu Enyuan , Ji Xiao , Zhu Yizhou , Han Fudong , Hwang Sooyeon , Liu Jue , Bak Seongmin , Ma Zhaohui , Gao Tao , Liou Sz-Chian , Bai Jianming , Yang Xiao-Qing , Mo Yifei , Xu Kang , Su Dong , Wang Chunsheng
Published: June 2018

Iron fluoride, an intercalation-conversion cathode for lithium ion batteries, promises a high theoretical energy density of 1922 Wh kg–1. However, poor electrochemical reversibility due to repeated breaking/reformation of metal fluoride bonds poses a grand challenge for its practical application. Here we report that both a high reversibility over 1000 cycles and a high capacity of 420 mAh g−1 can be realized by concerted doping of cobalt and oxygen into iron fluoride. In the doped nanorods, an energy density of ~1000 Wh kg−1 with a decay rate of 0.03% per cycle is achieved. The anion’s and cation’s co-substitutions thermodynamically reduce conversion reaction potential and shift the reaction from less-reversible intercalation-conversion reaction in iron fluoride to a highly reversible intercalation-extrusion reaction in doped material. The co-substitution strategy to tune the thermodynamic features of the reactions could be extended to other high energy conversion materials for improved performance.
Innovation and cumulative culture through tweaks and leaps in online programming contests
Authors: Miu Elena , Gulley Ned , Laland Kevin N. , Rendell Luke
Published: June 2018

The ability to build progressively on the achievements of earlier generations is central to human uniqueness, but experimental investigations of this cumulative cultural evolution lack real-world complexity. Here, we studied the dynamics of cumulative culture using a large-scale data set from online collaborative programming competitions run over 14 years. We show that, within each contest population, performance increases over time through frequent ‘tweaks’ of the current best entry and rare innovative ‘leaps’ (successful tweak:leap ratio = 16:1), the latter associated with substantially greater variance in performance. Cumulative cultural evolution reduces technological diversity over time, as populations focus on refining high-performance solutions. While individual entries borrow from few sources, iterative copying allows populations to integrate ideas from many sources, demonstrating a new form of collective intelligence. Our results imply that maximising technological progress requires accepting high levels of failure.
A modular transcriptional signature identifies phenotypic heterogeneity of human tuberculosis infection
Authors: Singhania Akul , Verma Raman , Graham Christine M. , Lee Jo , Tran Trang , Richardson Matthew , Lecine Patrick , Leissner Philippe , Berry Matthew P. R. , Wilkinson Robert J. , Kaiser Karine , Rodrigue Marc , Woltmann Gerrit , Haldar Pranabashis , O’Garra Anne
Published: June 2018

Whole blood transcriptional signatures distinguishing active tuberculosis patients from asymptomatic latently infected individuals exist. Consensus has not been achieved regarding the optimal reduced gene sets as diagnostic biomarkers that also achieve discrimination from other diseases. Here we show a blood transcriptional signature of active tuberculosis using RNA-Seq, confirming microarray results, that discriminates active tuberculosis from latently infected and healthy individuals, validating this signature in an independent cohort. Using an advanced modular approach, we utilise the information from the entire transcriptome, which includes overabundance of type I interferon-inducible genes and underabundance of IFNG and TBX21, to develop a signature that discriminates active tuberculosis patients from latently infected individuals or those with acute viral and bacterial infections. We suggest that methods targeting gene selection across multiple discriminant modules can improve the development of diagnostic biomarkers with improved performance. Finally, utilising the modular approach, we demonstrate dynamic heterogeneity in a longitudinal study of recent tuberculosis contacts.
A quantitative mass spectrometry-based approach to monitor the dynamics of endogenous chromatin-associated protein complexes
Authors: Papachristou Evangelia K. , Kishore Kamal , Holding Andrew N. , Harvey Kate , Roumeliotis Theodoros I. , Chilamakuri Chandra Sekhar Reddy , Omarjee Soleilmane , Chia Kee Ming , Swarbrick Alex , Lim Elgene , Markowetz Florian , Eldridge Matthew , Siersbaek Rasmus , D’Santos Clive S. , Carroll Jason S.
Published: June 2018

Understanding the dynamics of endogenous protein–protein interactions in complex networks is pivotal in deciphering disease mechanisms. To enable the in-depth analysis of protein interactions in chromatin-associated protein complexes, we have previously developed a method termed RIME (Rapid Immunoprecipitation Mass spectrometry of Endogenous proteins). Here, we present a quantitative multiplexed method (qPLEX-RIME), which integrates RIME with isobaric labelling and tribrid mass spectrometry for the study of protein interactome dynamics in a quantitative fashion with increased sensitivity. Using the qPLEX-RIME method, we delineate the temporal changes of the Estrogen Receptor alpha (ERα) interactome in breast cancer cells treated with 4-hydroxytamoxifen. Furthermore, we identify endogenous ERα-associated proteins in human Patient-Derived Xenograft tumours and in primary human breast cancer clinical tissue. Our results demonstrate that the combination of RIME with isobaric labelling offers a powerful tool for the in-depth and quantitative characterisation of protein interactome dynamics, which is applicable to clinical samples.
Network biology discovers pathogen contact points in host protein-protein interactomes
Authors: Ahmed Hadia , Howton T. C. , Sun Yali , Weinberger Natascha , Belkhadir Youssef , Mukhtar M. Shahid
Published: June 2018

In all organisms, major biological processes are controlled by complex protein–protein interactions networks (interactomes), yet their structural complexity presents major analytical challenges. Here, we integrate a compendium of over 4300 phenotypes with Arabidopsis interactome (AI-1MAIN). We show that nodes with high connectivity and betweenness are enriched and depleted in conditional and essential phenotypes, respectively. Such nodes are located in the innermost layers of AI-1MAIN and are preferential targets of pathogen effectors. We extend these network-centric analyses to Cell Surface Interactome (CSILRR) and predict its 35 most influential nodes. To determine their biological relevance, we show that these proteins physically interact with pathogen effectors and modulate plant immunity. Overall, our findings contrast with centrality-lethality rule, discover fast information spreading nodes, and highlight the structural properties of pathogen targets in two different interactomes. Finally, this theoretical framework could possibly be applicable to other inter-species interactomes to reveal pathogen contact points.
Helicase promotes replication re-initiation from an RNA transcript
Authors: Sun Bo , Singh Anupam , Sultana Shemaila , Inman James T. , Patel Smita S. , Wang Michelle D.
Published: June 2018

To ensure accurate DNA replication, a replisome must effectively overcome numerous obstacles on its DNA substrate. After encountering an obstacle, a progressing replisome often aborts DNA synthesis but continues to unwind. However, little is known about how DNA synthesis is resumed downstream of an obstacle. Here, we examine the consequences of a non-replicating replisome collision with a co-directional RNA polymerase (RNAP). Using single-molecule and ensemble methods, we find that T7 helicase interacts strongly with a non-replicating T7 DNA polymerase (DNAP) at a replication fork. As the helicase advances, the associated DNAP also moves forward. The presence of the DNAP increases both helicase’s processivity and unwinding rate. We show that such a DNAP, together with its helicase, is indeed able to actively disrupt a stalled transcription elongation complex, and then initiates replication using the RNA transcript as a primer. These observations exhibit T7 helicase’s novel role in replication re-initiation.
NEK7 regulates dendrite morphogenesis in neurons via Eg5-dependent microtubule stabilization
Authors: Freixo Francisco , Martinez Delgado Paula , Manso Yasmina , Sánchez-Huertas Carlos , Lacasa Cristina , Soriano Eduardo , Roig Joan , Lüders Jens
Published: June 2018

Organization of microtubules into ordered arrays is best understood in mitotic systems, but remains poorly characterized in postmitotic cells such as neurons. By analyzing the cycling cell microtubule cytoskeleton proteome through expression profiling and targeted RNAi screening for candidates with roles in neurons, we have identified the mitotic kinase NEK7. We show that NEK7 regulates dendrite morphogenesis in vitro and in vivo. NEK7 kinase activity is required for dendrite growth and branching, as well as spine formation and morphology. NEK7 regulates these processes in part through phosphorylation of the kinesin Eg5/KIF11, promoting its accumulation on microtubules in distal dendrites. Here, Eg5 limits retrograde microtubule polymerization, which is inhibitory to dendrite growth and branching. Eg5 exerts this effect through microtubule stabilization, independent of its motor activity. This work establishes NEK7 as a general regulator of the microtubule cytoskeleton, controlling essential processes in both mitotic cells and postmitotic neurons.