bluuebunny/crossref_metadata_2025 huggingface dataset:
Spark resistance under high-speed gas flow in the oscillatory damped regime of discharge
Authors: Li Xiaoang , Zhang Yuzhao , Ma Chaoqun , Liu Lin
Published: July 2018

Applying a high-speed gas flow is an effective method to exclude residual plasma and expedite the insulation recovery of high-power spark gaps and can extend their applications to higher-repetition fields. In this paper, the subject of interest is a spark gap repetitively working in a low-damping oscillatory regime of discharge. The influence of gas flow for performance regulation on spark resistance was investigated based on both electrical and optical diagnoses. A high-speed air flow ranging from 0 to 100 m/s was applied by a Laval nozzle, and a significant increase in the damping ratio of the discharge current, implying an increase in spark resistance, was observed with increasing speed of gas flow. According to the optical diagnosis results, the influence of gas flow on the spark channel had two main aspects: configuration and temperature. Although the electron temperature under gas flow showed a trend of slight increase, indicating an increase in the conductivity of the spark channel, the high-speed gas flow could greatly stretch and thin the discharge channel, which was the dominant factor and resulted in an increase in spark resistance.
Enhanced current-perpendicular-to-plane giant magnetoresistance by improvement of atomic order of Co2FeSi Heusler alloy film through Ag doping
Authors: Li Songtian , Sakuraba Yuya , Sasaki Taisuke , Chen Jiamin , Bosu Subrojati , Hono Kazuhiro
Published: July 2018

We investigated the effect of Ag doping on atomic order and spin polarization of Co2FeSi Heusler alloy thin films. The Co2FeSi film doped with 3at.%-Ag showed improved degree of B2- and L21-ordering after thermal annealing comparing to Co2FeSi film. Negative sign of anisotropic magnetoresistance suggests the half-metallic nature of Ag-doped Co2FeSi film after annealing at a relatively low temperature of 300 °C. The current-perpendicular-to-plane pseudo spin-valves using the Ag-doped Co2FeSi ferromagnetic (FM) electrodes showed about 1.2 times larger MR ratio than that using the Co2FeSi FM electrodes, reflecting an enhanced spin polarization in Ag-doped Co2FeSi film. Micro-structure analysis revealed the doped Ag was rejected out of Co2FeSi layer after annealing. This study suggests Ag doping to Co-based Heusler compound having no/few solubility with Ag is beneficial for realizing spin-valves with high output at moderate annealing conditions.
Remote access to electrical conductivity by charge attachment from an ambient pressure plasma
Authors: Wiemer Jan L. , Weitzel Karl-Michael
Published: July 2018

A technique for investigating the electrical conductivity of condensed matter based on softly attaching charge carriers from a plasma to the front side of a sample is presented. The attachment of the charge carriers induces an electric surface potential and consequently charge migration inside the sample which is in contact with a single metal electrode at the backside. The measurement of the current allows determining the electrical conductivity of the sample. The plasma employed is generated by focusing femtosecond laser pulses in air at ambient pressure. As a proof-of-principle, we demonstrate the measurement of the ionic conductivity of a D263T glass and its activation energy. The analysis reveals very good agreement with independent previous measurements. The approach presented is operative in positive and negative polarities. It is in principle extendable to a wide range of plasma media and pressures and can thus be expected to be applicable for remote material testing.
The pugometer: an evaluation of a new tool for assessing treading damage of pasture soils and comparisons with other methods
Authors: Howes J. A. , Hanly J. A. , Horne D. J. , Hedley M. J. , Irwin M.
Published: July 2018

Treading damage inflicted by grazing animals degrades soil physical quality, increases sediment and nutrient loss to water, and reduces pasture yield. The extent or severity of treading damage can be assessed using several methods such as roller chain, depth of pug, and visual scoring. However, the ability of these methods to assess treading damage, and their relative merits, have not previously been compared. Four methods of measuring treading damage are compared in this study including the three methods mentioned and a new tool called the pugometer, which was developed to measure treading damage in a spatially explicit manner. These comparisons were conducted on three paddocks at Massey University’s Dairy 4 farm near Palmerston North, Manawatu, New Zealand which had sustained treading damage of varying levels during grazing in wet conditions.
All four methods were able to identify varying degrees of treading damage competently with strong correlations between them (R2 = 0.72–0.87). Therefore, the selection of the most appropriate method to assess treading damage will depend on the circumstances. Visual scoring was the quickest and simplest method to use over a large area, and so could be employed easily by a farmer. The pugometer provides a quantitative measure of the spatial variability of treading damage and so would be a useful research tool. The depth of pug and roller chain methods are reliable but much more time consuming and therefore are only practicable as research tools for small plot studies. Following a treading event, the pugometer was able to monitor the recovery of surface roughness in a spatially explicit and rapid manner.
Additional keywords: depth of pug, quantifying pugging, roller chain, visual assessment.
Heterosubtypic influenza protection elicited by double-layered polypeptide nanoparticles in mice
Authors: Deng Lei , Chang Timothy Z. , Wang Ye , Li Song , Wang Shelly , Matsuyama Shingo , Yu Guoying , Compans Richard W. , Li Jian-Dong , Prausnitz Mark R. , Champion Julie A. , Wang Bao-Zhong
Published: July 2018

Significance

Mismatched seasonal influenza vaccines are low efficacy and provide limited protection against circulating strains. A universal influenza vaccine that can induce broadly cross-protective immunity is urgently needed. Here, we have developed a layered peptide-only nanoparticle vaccine delivered by dissolvable microneedle patches. Immunizations with the vaccine candidates elicited robust long-lasting protective immune responses in mice. We found that the unique in vivo biodistribution feature of the nanoparticles correlated with the long-term immunity. This vaccine approach can be applied to develop peptide-based vaccines for different pathogens.
Functions of the COPII gene paralogs SEC23A and SEC23B are interchangeable in vivo
Authors: Khoriaty Rami , Hesketh Geoffrey G. , Bernard Amélie , Weyand Angela C. , Mellacheruvu Dattatreya , Zhu Guojing , Hoenerhoff Mark J. , McGee Beth , Everett Lesley , Adams Elizabeth J. , Zhang Bin , Saunders Thomas L. , Nesvizhskii Alexey I. , Klionsky Daniel J. , Shavit Jordan A. , Gingras Anne-Claude , Ginsburg David
Published: July 2018

Significance

In humans, SEC23B deficiency results in congenital dyserythropoietic anemia type II, a disease of abnormal red blood cell development, while SEC23A deficiency results in cranio-lenticulo-sutural-dysplasia, a disease characterized by bone abnormalities due to defective collagen secretion (but no red blood cell defect). In this study, we show that SEC23A and SEC23B overlap in function, and that the disparate phenotypes of SEC23A/SEC23B deficiency within and across species are likely due to evolutionary shifts in gene-expression programs, rather than distinct functions of the SEC23 paralogs. Our studies provide a rationale for increased SEC23A or SEC23B expression as a therapeutic strategy for congenital dyserythropoietic anemia type II or cranio-lenticulo-sutural-dysplasia, respectively.
Intermetallic-strengthened nanocrystalline bainitic steel
Authors: Hulme-Smith C. N. , Ooi S. W. , Bhadeshia H. K. D. H.
Published: July 2018

A new thermally stable, nanocrystalline bainitic steel has been developed, rich in nickel and aluminium. During tempering, it is expected that a significant quantity of intermetallic precipitates will form. This was confirmed by X-ray diffractometry, scanning transmission electron microscopy, Fourier transform analysis of atomic column images, energy dispersive X-ray spectroscopy and selected area electron diffraction. These are the first intermetallics to be produced in a nanocrystalline bainitic steel.
Foreshore beach sand as a reservoir and source of total phosphorus in Lake Ontario
Authors: Staley Zachery R. , He Dennis D. , Shum Phoenix , Vender Reid , Edge Thomas A.
Published: July 2018

Many regions around the Great Lakes have been designated Areas of Concern as a result of consistent water quality problems from pollutants like phosphorus and Escherichia coli, which cause eutrophication, beach postings and Beneficial Use Impairments. While foreshore beach sand is a potential reservoir for E. coli, there is less understanding of whether it might also be a reservoir and source of phosphorus for adjacent beach waters. We measured levels of E. coli, total phosphorus and soluble reactive phosphorus at Sunnyside and Rouge Beaches in the Toronto and Region Area of Concern, and stormwater outfalls in the adjacent Humber and Rouge Rivers within their beachsheds. Additionally, we used microbial source tracking assays to detect human and gull fecal contamination. Soluble reactive phosphorus concentrations were highest in stormwater outfalls, with concentrations as high as 556 µg l−1 at an outfall in the Sunnyside beachshed, and 4780 µg l−1 at an outfall in the Rouge beachshed. In contrast, the highest total phosphorus concentrations were typically found in foreshore beach sand pore water and were more associated with gull fecal contamination. Beach sand total phosphorus levels were as high as 10,600 µg l−1 at Sunnyside Beach, although the highest total phosphorus concentration measured (25,600 µg l−1) was in a Rouge River outfall. Concentrations of total phosphorus in outfalls were significantly correlated with concentrations of E. coli in both beachsheds and the human microbial source tracking marker in the Sunnyside beachshed outfalls. These results indicate that stormwater outfalls with sewage cross-contamination can deliver high concentrations of total phosphorus, soluble reactive phosphorus and fecal bacterial contamination to associated beachsheds. Further, similar to E. coli, foreshore beach sand can act as a reservoir of total phosphorus and a source for adjacent water bodies via wave action or groundwater discharge. High phosphorus inputs from beach sand could contribute localized changes to microbial communities and unique eutrophication effects along beach shorelines.
Evaluation of cross-platform and interlaboratory concordance via consensus modelling of genomic measurements
Authors: Peters Timothy J , French Hugh J , Bradford Stephen T , Pidsley Ruth , Stirzaker Clare , Varinli Hilal , Nair Shalima , Qu Wenjia , Song Jenny , Giles Katherine A , Statham Aaron L , Speirs Helen , Speed Terence P , Clark Susan J
Published: July 2018

Motivation

A synoptic view of the human genome benefits chiefly from the application of nucleic acid sequencing and microarray technologies. These platforms allow interrogation of patterns such as gene expression and DNA methylation at the vast majority of canonical loci, allowing granular insights and opportunities for validation of original findings. However, problems arise when validating against a “gold standard” measurement, since this immediately biases all subsequent measurements towards that particular technology or protocol. Since all genomic measurements are estimates, in the absence of a ”gold standard” we instead empirically assess the measurement precision and sensitivity of a large suite of genomic technologies via a consensus modelling method called the row-linear model. This method is an application of the American Society for Testing and Materials Standard E691 for assessing interlaboratory precision and sources of variability across multiple testing sites. Both cross-platform and cross-locus comparisons can be made across all common loci, allowing identification of technology- and locus-specific tendencies.

Results

We assess technologies including the Infinium MethylationEPIC BeadChip, whole genome bisulfite sequencing (WGBS), two different RNA-Seq protocols (PolyA+ and Ribo-Zero) and five different gene expression array platforms. Each technology thus is characterised herein, relative to the consensus. We showcase a number of applications of the row-linear model, including correlation with known interfering traits. We demonstrate a clear effect of cross-hybridisation on the sensitivity of Infinium methylation arrays. Additionally, we perform a true interlaboratory test on a set of samples interrogated on the same platform across twenty-one separate testing laboratories.

Availability and implementation

A full implementation of the row-linear model, plus extra functions for visualisation, are found in the R package consensus at https://github.com/timpeters82/consensus.

Supplementary information

Supplementary data are available at Bioinformatics online.
Hot-starting software containers for STAR aligner
Authors: Zhang Pai , Hung Ling-Hong , Lloyd Wes , Yeung Ka Yee
Published: July 2018

Background

Using software containers has become standard practice to reproducibly deploy and execute biomedical workflows on the cloud. However, some applications that contain time-consuming initialization steps will produce unnecessary costs for repeated executions.

Findings

We demonstrate that hot-starting from containers that have been frozen after the application has already begun execution can speed up bioinformatics workflows by avoiding repetitive initialization steps. We use an open-source tool called Checkpoint and Restore in Userspace (CRIU) to save the state of the containers as a collection of checkpoint files on disk after it has read in the indices. The resulting checkpoint files are migrated to the host, and CRIU is used to regenerate the containers in that ready-to-run hot-start state. As a proof-of-concept example, we create a hot-start container for the spliced transcripts alignment to a reference (STAR) aligner and deploy this container to align RNA sequencing data. We compare the performance of the alignment step with and without checkpoints on cloud platforms using local and network disks.

Conclusions

We demonstrate that hot-starting Docker containers from snapshots taken after repetitive initialization steps are completed significantly speeds up the execution of the STAR aligner on all experimental platforms, including Amazon Web Services, Microsoft Azure, and local virtual machines. Our method can be potentially employed in other bioinformatics applications in which a checkpoint can be inserted after a repetitive initialization phase.
Risk of health morbidity for the uninsured: 10-year evidence from a large hospital center in Boston, Massachusetts
Authors: Chen Zhaoyi , Min Jae , Bian Jiang , Wang Mo , Zhou Le , Prosperi Mattia
Published: July 2018

Objective

To investigate the independent contribution of insurance status toward the risk of diagnosis of specific clinical comorbidities for individuals admitted to intensive care unit (ICU).

Design

Retrospective analysis of secondary database.

Setting

Ten years of public de-identified ICU electronic medical records from a large hospital in USA.

Participants

Patients (18–65 years old) who had private insurance or no insurance were extracted from the database.

Main outcome measures

Independent association of insurance status (uninsured vs. privately insured) with the risk of diagnosis of specific clinical comorbidities.

Results

Among 14 268 (from 11 753 patients) admissions to ICU between 2001 and 2012, 96% of them were covered by private insurance. Patients with private insurance had higher proportion of females, married, White race, longer ICU stay and more procedures during stay, and fewer deaths. A lower CCI was observed in uninsured patients. At multivariable analysis, uninsured patients had higher odds of death and of admissions for accidental falls, substance or alcohol abuse.

Conclusions

Patients with no insurance coverage were at higher risk of death and of admission for physical and substance-related injury. We did not observe a higher risk for acute life-threatening diseases such as myocardial infarction or kidney failure. The lower CCI observed in the uninsured may be explained by under diagnosis or voluntary withdrawal from coverage in the pre-Affordable Care Act era. Replication of findings is warranted in other populations, among those with government-subsidized insurance and in the procedure/prescription domains.
Rotational variation of the linear polarization of the asteroid (3200) Phaethon as evidence for inhomogeneity in its surface properties
Authors: Borisov G , Devogèle M , Cellino A , Bagnulo S , Christou A , Bendjoya Ph , Rivet J-P , Abe L , Vernet D , Donchev Z , Krugly Yu , Belskaya I , Bonev T , Steeghs D , Galloway D , Dhillon V , O’Brien P , Pollacco D , Poshyachinda S , Ramsay G , Thrane E , Ackley K , Rol E , Ulaczyk K , Cutter R , Dyer M
Published: July 2018

Asteroid (3200) Phaethon is a Near-Earth Apollo asteroid with an unusual orbit that brings it closer to the Sun than any other known asteroid. Its last close approach to the Earth was in 2017 mid-December and the next one will be on 2026 October. Previous rotationally time-resolved spectroscopy of Phaethon showed that its spectral slope is slightly bluish, in agreement with its B/F taxonomic classification, but at some rotational phases, it changes to slightly reddish. Motivated by this result, we performed time-resolved imaging polarimetry of Phaethon during its recent close approach to the Earth. Phaethon has a spin period of 3.604 h, and we found a variation of the linear polarization with rotation. This seems to be a rare case in which such variation is unambiguously found, also a consequence of its fairly large amplitude. Combining this new information with the brightness and colour variation as well as previously reported results from Arecibo radar observations, we conclude that there is no variation of the mineralogy across the surface of Phaeton. However, the observed change in the linear polarization may be related to differences in the thickness of the surface regolith in different areas or local topographic features.
Predictors of Missed Hepatitis C Intake Appointments and Failure to Establish Hepatitis C Care Among Patients Living With HIV
Authors: Cachay Edward R , Hill Lucas , Torriani Francesca , Ballard Craig , Grelotti David , Aquino Abigail , Christopher Mathews W
Published: July 2018

Background

We estimated and characterized the proportion of patients living with HIV (PLWH) who missed hepatitis C (HCV) intake appointments and subsequently failed to establish HCV care.

Methods

Logistic regression analyses were used to identify factors associated with missed HCV intake appointments and failure to establish HCV care among PLWH referred for HCV treatment between January 2014 and December 2017. In addition to demographics, variables included HIV treatment characteristics, type of insurance, liver health status, active alcohol or illicit drug use, unstable housing, and history of a mental health disorder (MHD).

Results

During the study period, 349 new HCV clinic appointments were scheduled for 202 unduplicated patients. Approximately half were nonwhite, and 80% had an undetectable HIV viral load. Drug use (31.7%), heavy alcohol use (32.8%), and MHD (37.8%) were prevalent. Over the 4-year period, 21.9% of PLWH referred for HCV treatment missed their HCV intake appointment. The proportion increased each year, from 17.2% in 2014 to 25.4% in 2017 (P = .021). Sixty-six of the 202 newly referred HCV patients (32.7%) missed their first HCV appointment, and 28 of these (42.4%) failed to establish HCV care. Having a history of MHD, CD4 <200, ongoing drug use, and being nonwhite were independent predictors of missing an intake HCV appointment. The strongest predictor of failure to establish HCV care was having a detectable HIV viral load.

Conclusions

The proportion of PLWH with missed HCV appointments increased over time. HCV elimination among PLWH may require integrated treatment of MHD and substance use.
Epidemiology and Clinical Features of Invasive Fungal Infection in a US Health Care Network
Authors: Webb Brandon J , Ferraro Jeffrey P , Rea Susan , Kaufusi Stephanie , Goodman Bruce E , Spalding James
Published: July 2018

Background

A better understanding of the epidemiology and clinical features of invasive fungal infection (IFI) is integral to improving outcomes. We describe a novel case-finding methodology, reporting incidence, clinical features, and outcomes of IFI in a large US health care network.

Methods

All available records in the Intermountain Healthcare Enterprise Data Warehouse from 2006 to 2015 were queried for clinical data associated with IFI. The resulting data were overlaid in 124 different combinations to identify high-probability IFI cases. The cohort was manually reviewed, and exclusions were applied. European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group Consensus Group definitions were adapted to categorize IFI in a broad patient population. Linear regression was used to model variation in incidence over time.

Results

A total of 3374 IFI episodes occurred in 3154 patients. The mean incidence was 27.2 cases/100 000 patients per year, and there was a mean annual increase of 0.24 cases/100 000 patients (P = .21). Candidiasis was the most common (55%). Dimorphic fungi, primarily Coccidioides spp., comprised 25.1% of cases, followed by Aspergillus spp. (8.9%). The median age was 55 years, and pediatric cases accounted for 13%; 26.1% of patients were on immunosuppression, 14.9% had autoimmunity or immunodeficiency, 13.3% had active malignancy, and 5.9% were transplant recipients. Lymphopenia preceded IFI in 22.1% of patients. Hospital admission occurred in 76.2%. The median length of stay was 16 days. All-cause mortality was 17.0% at 42 days and 28.8% at 1 year. Forty-two-day mortality was highest in Aspergillus spp. (27.5%), 20.5% for Candida, and lowest for dimorphic fungi (7.5%).

Conclusions

In this population, IFI was not uncommon, affected a broad spectrum of patients, and was associated with high crude mortality.
Adenovirus Type 21 Outbreak Among Lung Transplant Patients at a Large Tertiary Care Hospital
Authors: Philo Sarah E , Anderson Benjamin D , Costa Sylvia F , Henshaw Nancy , Lewis Sarah S , Reynolds John M , Jayakumar Jayanthi , Su Yvonne C F , Gray Gregory C
Published: July 2018

Here we summarize an April 2016, 7-patient cluster of human adenovirus (HAdV) infections in a cardiothoracic surgery intensive care unit. We show that the patients were infected with a single HAdV21b type. Rapid HAdV typing diagnostics and effective antiviral interventions are needed for immunocompromised patients suffering from HAdV infections.
Anatomic Nuances of the Ophthalmic Artery Origin from a Ventral Viewpoint: Considerations and Implications for Endoscopic Endonasal Surgery
Authors: Naudy Cristian A , Yanez-Siller Juan C , Mesquita Filho Paulo M , Gomez G. Matias , Otto Bradley A , Carrau Ricardo L , Prevedello Daniel M
Published: July 2018

BACKGROUND

The origin of the ophthalmic artery is within the surgical field of endoscopic endonasal approaches (EEAs) to the suprasellar and parasellar regions. However, its anatomy from the endoscopic point-of-view has not been adequately elucidated.

OBJECTIVE

To highlight the anatomy of the ophthalmic artery origin from an endoscopic endonasal perspective.

METHODS

The origin of the ophthalmic artery was studied bilaterally under endoscopic visualization, after performing transplanum/transtubercular EEAs in 17 cadaveric specimens (34 arteries). Anatomic relationships relevant to surgery were evaluated. To complement the cadaveric findings, the ophthalmic artery origin was reviewed in 200 “normal” angiographic studies.

RESULTS

On the right side, 70.6% of ophthalmic arteries emerged from the superior aspect, while 17.6% and 11.8% emerged from the superomedial and superolateral aspects of the intradural internal carotid artery, respectively. On the left, 76.5%, 17.6%, and 5.9% of ophthalmic arteries emerged from the superior, superomedial, and superolateral aspects of the internal carotid, respectively. Similar findings were observed on angiography. All ophthalmic arteries emerged at the level of the medial opticocarotid recess. Overall, 47%, 26.5%, and 26.5% of ophthalmic arteries (right and left) were inferolateral, inferior, and inferomedial to the intracranial optic nerve segment, respectively. On both sides, the intracranial length of the ophthalmic artery ranged from 1.5 to 4.5 mm (mean: 2.90 ± standard deviation of 0.74 mm).

CONCLUSION

Awareness of the endoscopic nuances of the ophthalmic artery origin is paramount to minimize the risk of sight-threatening neurovascular injury during EEAs to the suprasellar and parasellar regions.
Cloning, gene regulation, and neuronal proliferation functions of novel N‐terminal–truncated carboxypeptidase E/neurotrophic factor‐αl variants in embryonic mouse brain
Authors: Xiao Lan , Yang Xuyu , Sharma Vinay Kumar , Loh Y. Peng
Published: July 2018

Carboxypeptidase E (CPE), an exopeptidase involved in proneuropeptide processing, is also a neurotrophic factor, named neurotrophic factor‐α1 (NF‐α1) and has important roles in neuroprotection, stem cell differentiation, and neurite outgrowth, independent of enzymatic activity. Additionally, an N‐terminal–truncated CPE/NF‐α1 variant, (CPE/NF‐α1)‐ΔN, proposed from bioinformatic analysis of GenBank (National Center for Biotechnology Information, Bethesda, MD, USA) DNA sequences and encoding a 40‐kDa protein, has been found to be exclusively expressed in embryonic neurons. To investigate the function of (CPEZNF‐α1)‐ΔN in neurodevelopment, we first cloned (CPEZNF‐α1)‐ΔN transcripts from an embryonic mouse brain. A rapid amplification of cDNA ends assay, DNA sequencing, and Northern blot revealed 1.9‐ and 1.73‐kb transcripts, which encoded 47‐ and 40‐kDa (CPE/NF‐α1)‐ΔN proteins, respectively. Those proteins were expressed in embryonic mouse brain. Expression of the 2 (CPE/NF‐α1)‐ΔN mRNAs surged at embryonic d 10.5, correlating with the time of neurogenesis in the developing brain and also at postnatal d 1. HT22 cells, a mouse hippocampal cell line, transduced with 40 kDa (CPE/NF‐α1)‐ΔN up‐regulated expression of genes involved in embryonic neurodevelopment: insulin‐like growth factor binding protein 2 (IGFBP2), death‐associated protein 1, and ephrin A1, which regulate proliferation, programmed cell death, and neuronal migration, respectively. HT22 cells and embryonic cortical neurons overexpressing 40 kDa (CPE/NF‐α1)‐ΔN exhibited enhanced proliferation, which was inhibited by IGFBP2 short interfering RNA treatment. Thus, 40 kDa (CPE/NF‐α1)‐ΔN has an important, enzymatically independent role in the regulation of genes critical for neurodevelopment.—Xiao, L., Yang, X., Sharma, V. K., Loh, Y. P. Cloning, gene regulation, and neuronal proliferation functions of novel N‐terminal–truncated carboxypeptidase E/neurotrophic factor‐α1 variants in embryonic mouse brain. FASEB J. 33, 808–820 (2019). www.fasebj.org
Juvenile hormone–dependent Kazal‐type serine protease inhibitor Greglin safeguards insect vitellogenesis and egg production
Authors: Guo Wei , Wu Zhongxia , Yang Libin , Cai Zhaokui , Zhao Lianfeng , Zhou Shutang
Published: July 2018

In addition to preventing insect metamorphosis, juvenile hormone (JH) is known to stimulate aspects of insect reproduction. However, the molecular mechanisms of JH action in insect reproduction remain largely unknown. By reanalyzing the transcriptomic data from adults and other developmental stages of the migratory locust Locusta migratoria, we identified a gene coding for Kazal‐type protease inhibitor, previously named Greglin. Greglin is specifically expressed in adult females and most abundant in the fat body and ovaries. Interestingly, Greglin is among the top 3 of highly expressed genes in adult female locusts, after 2 vitellogenin (Vg) genes. Greglin is induced by JH and expressed at remarkably high levels in the vitellogenic stage. Knockdown of Greglin in adult female locusts results in accelerated degradation of serine protease substrate and significantly reduced levels of Greglin protein in hemolymph and ovaries. The consequent phenotypes include blocked oocyte maturation, arrested ovarian growth and shrunken follicular epithelium, as well as declines in egg number and hatchability. The data provide the first evidence, to our knowledge, that JH‐dependent Greglin is involved in locust vitellogenesis and oocyte maturation likely by protecting vitellogenesis and other forms of yolk precursors from proteolysis. The result offers new insights into the regulation of JH and function of protease inhibitors in insect vitellogenesis, oocyte maturation and fecundity.—Guo, W., Wu, Z., Yang, L., Cai, Z., Zhao, L., Zhou, S. Juvenile hormone–dependent Kazal‐type serine protease inhibitor Greglin safeguards insect vitellogenesis and egg production. FASEB J. 33, 917–927 (2019). www.fasebj.org
Sexually dimorphic gene expression and transcriptome evolution provides mixed evidence for a fast-Z effect inHeliconius
Authors: Pinharanda A , Rousselle M , Martin SH , Hanly JJ , Davey JW , Kumar S , Galtier N , Jiggins CD
Published: July 2018

Sex chromosomes have different evolutionary properties as compared to the autosomes due to their hemizygous nature. In particular, recessive mutations are more readily exposed to selection, which can lead to faster rates of molecular evolution. Here, we report patterns of gene expression and molecular evolution in the sex chromosomes of a group of tropical butterflies. We first improved the completeness of theHeliconius melpomenereference annotation, a neotropical butterfly with a ZW sex determination system. Then we sequenced RNA from male and female whole abdomens and female ovary and gut tissue to identify sex and tissue specific gene expression profiles inH. melpomene. Using these expression profiles we compare sequence divergence and polymorphism, the strength of positive and negative selection and rates of adaptive evolution for Z and autosomal genes between two species ofHeliconiusbutterflies,H. melpomeneandH. erato.

We show that the rate of adaptive substitutions is higher for Z as compared to autosomal genes, but contrary to expectation it is also higher for male as compared to female biased genes. There is therefore mixed evidence that hemizygosity influences the rate of adaptive substitutions. Additionally, we find no significant increase in the rate of adaptive evolution or purifying selection on genes expressed in ovary tissue, a heterogametic specific tissue. Together our results provide limited support for fast-Z evolution. This contributes to a growing body of literature from other ZW systems that also provide mixed evidence for a fast-Z effect.
Considerations for imaging thick, low contrast, and beam sensitive samples with liquid cell transmission electron microscopy
Authors: Moser Trevor H. , Shokuhfar Tolou , Evans James E.
Published: July 2018

Transmission electron microscopy of whole cells is hindered by the inherently large thickness and low atomic contrast intrinsic of cellular material. Liquid cell transmission electron microscopy allows samples to remain in their native hydrated state and may permit visualizing cellular dynamics in-situ. However, imaging biological cells with this approach remains challenging and identifying an optimal imaging regime using empirical data would help foster new advancements in the field. Recent questions about the role of the electron beam inducing morphological changes or damaging cellular structure and function necessitates further investigation of electron beam-cell interactions, but is complicated by variability in imaging techniques used across various studies currently present in literature. The necessity for using low electron fluxes for imaging biological samples requires finding an imaging strategy which produces the strongest contrast and signal to noise ratio for the electron flux used. Here, we experimentally measure and evaluate signal to noise ratios and damage mechanisms between liquid and cryogenic samples for cells using multiple electron imaging modalities all on the same instrument and with equivalent beam parameters to standardize the comparison. We also discuss considerations for optimal electron microscopy imaging conditions for future studies on whole cells within liquid environments.
Modeling the MYC-driven normal-to-tumour switch in breast cancer
Authors: Lourenco Corey , Kalkat Manpreet , Houlahan Kathleen E. , Melo Jason De , Longo Joseph , Done Susan J. , Boutros Paul C. , Penn Linda Z.
Published: July 2018

The potent MYC oncoprotein is deregulated in many human cancers, including breast carcinoma, and is associated with aggressive disease. To understand the mechanisms and vulnerabilities of MYC-driven breast cancer, we have generated anin vivomodel that mimics human disease in response to MYC deregulation. MCF10A cells ectopically expressing a common breast cancer mutation in the PI3 kinase pathway (PIK3CAH1047R) lead to the development of organized acinar structures in mice. However, expressing both PIK3CAH1047Rand deregulated-MYC lead to the development of invasive ductal carcinoma, thus creating a model in which a MYC-dependent normal-to-tumour switch occursin vivo. These MYC-driven tumors exhibit classic hallmarks of human breast cancer at both the pathological and molecular levels. Moreover, tumour growth is dependent upon sustained deregulated MYC expression, further demonstrating addiction to this potent oncogene and regulator of gene transcription. We therefore provide a MYC-dependent human model of breast cancer which can be assayed forin vivotumour initiation, proliferation, and transformation from normal breast acini into invasive breast carcinoma. Taken together, we anticipate that this novel MYC-driven transformation model will be a useful research tool to both better understand MYC’s oncogenic function and identify therapeutic vulnerabilities.

Conflict of interest statement

The authors declare no potential conflicts of interest.
Effect ofde novotranscriptome assembly on transcript quantification
Authors: Hsieh Ping-Han , Oyang Yen-Jen , Chen Chien-Yu
Published: July 2018

Background

Correct quantification of transcript expression is essential to understand the functional products of the genome in different physiological conditions and developmental stages. Recently, the development of high-throughput RNA sequencing (RNA-Seq) allows the researchers to perform transcriptome analysis for the organisms without the reference genome and transcriptome. For such projects,de novotranscriptome assembly must be carried out prior to quantification. However, a large number of erroneous contigs produced by the assemblers might result in unreliable estimation on the abundance of transcripts. In this regard, this study comprehensively investigates how assembly quality affects the performance of quantification for RNA-Seq analysis based onde novotranscriptome assembly.

Results

Several important factors that might seriously affect the accuracy of the RNA-Seq analysis were thoroughly discussed. First, we found that the assemblers perform comparatively well for the transcriptomes with lower biological complexity. Second, we examined the over-extended and incomplete contigs, and then demonstrated that assembly completeness has a strong impact on the estimation of contig abundance. Lastly, we investigated the behavior of the quantifiers with respect to sequence ambiguity which might be originally present in the transcriptome or accidentally produced by assemblers. The results suggest that the quantifiers often over-estimate the expression of family-collapse contigs and under-estimate the expression of duplicated contigs. For organisms without reference transcriptome, it remained challenging to detect the inaccurate abundance estimation on family-collapse contigs. On the contrary, we observed that the situation of under-estimation on duplicated contigs can be warned through analyzing the read distribution of the duplicated contigs.

Conclusions

In summary, we explicated the behavior of quantifiers when erroneous contigs are present and we outlined the potential problems that the assemblers might cause for the downstream analysis of RNA-Seq. We anticipate the analytic results conducted in this study provides valuable insights for future development of transcriptome assembly and quantification.

Availability

we proposed an open-source Python based package QuantEval that builds connected components for the assembled contigs based on sequence similarity and evaluates the quantification results for each connected component. The package can be downloaded fromhttps://github.com/dn070017/QuantEval.
Developmental fidelity imposed by the RGL-1 “Balanced Switch” mediating opposing signals
Authors: Shin Hanna , Braendle Christian , Monahan Kimberly B. , Kaplan Rebecca E.W. , Zand Tanya P. , Mote F. Sefakor , Craig DeSean R. , Peters Eldon , Reiner David J.
Published: July 2018

The sixC. elegansvulval precursor cells (VPCs) are induced to form the 30-30-20-Γ-20-3° pattern of cell fates with high fidelity. In response to EGF signal, the LET-60/Ras-LIN-45/Raf-MEK-2/MEK-MPK-1/ERK canonical MAP kinase cascade is necessary to induce 1° fate and synthesis of DSL ligands. In turn, LIN-12/Notch signal is necessary to induce neighboring cells to become 2°. We previously showed that, in response to lower dose of EGF signal, the modulatory LET-60/Ras-RGL-1/RalGEF-RAL-1/Ral signal promotes 2° fate in support of LIN-12. In this study we identify two key differences between RGL-1 and RAL-1 functions. First, deletion of RGL-1 confers no overt developmental defects, while previous studies showed RAL-1 to be essential for viability and fertility. From this observation we hypothesize that the developmentally essential functions of RAL-1 are independent of upstream activation. Second, RGL-1 plays opposing and genetically separable roles in VPC fate patterning. RGL-1 promotes 2° fate via canonical GEF-dependent activation of RAL-1 and 1° fate via a non-canonical GEF-independent activity. Our genetic epistasis experiments are consistent with RGL-1 functioning in the modulatory 1°-promoting AGE-1/PI3-Kinase-PDK-1-AKT-1 cascade. Additionally, animals without RGL-1 experience 15-fold higher rates of VPC patterning errors compared to the wild type. Yet VPC patterning in RGL-1 deletion mutants is not more sensitive to environmental perturbations. We propose that RGL-1 functions as a “Balanced Switch” that orchestrates opposing 1°- and 2°-promoting modulatory cascades to decrease inappropriate fate decisions. We speculate that such switches are broadly conserved but mostly masked by paralog redundancy or essential genes.
Statistical optimization of culture conditions to improve cell density ofKomagataeibacter medellinensisNBRC 3288: the first step towards to optimize bacterial cellulose production
Authors: Molina-Ramírez Carlos , Zuluaga Robin , Castro Cristina , Gañán Piedad
Published: July 2018

The cell density yield ofKomagataeibacter medellinensisNBRC 3288 was optimized applying response surface methodology (RSM) for the first time with this strain. Four factors were evaluated: glucose, initial pH, MgSO4and KH2PO4, these were analyzed in a fractional factorial design to verify which were important to cell density yield. The best treatment assayed showed a yield of 1.09 OD600and analysis of variance (ANOVA) selected glucose, inital pH and KH2PO4as the significant factors. Next, a new experimental region with center point at glucose 0.5 %(wt./v), initial pH at 5.58 and KH2PO40.058 %(wt./v) was obtained by steepest ascent method and used to optimize biomass yield by Box-Behnken design. The results indicate that the optimum culture medium conditions predicted by the mathematical model (R2adj=72.09 %) were: glucose, 0.54 %(wt./v); peptone, 0.5 %(wt./v); yeast extract, 0.5 %(wt./v); KH2PO4, 0.059 %(wt./v); MgSO4, 0.025 %(wt./v); NaH2PO4, 0.267 %(wt./v) and pH, 5.18 (adjusted with citric acid, 0.2 %(wt./v)) to obtain an optimum cell density yield of 2.85 OD600with an improve of 68 % respect to the best result obtained at the begin, as well as μmimproved 34.78 % and a reduction in cost of culture medium due to glucose concentration reduction of 75 %.

Importance

Despite the important role of producer-strain play in bacterial cellulose production, until now there is not anu report about how to improve cell density, as a primary stage, that allows reach higher production of BC in later stages. In this study, was optimized the growth conditions ofK. medellinensis(a BC producer in acid pH) in order to increase the cell density, as the primer stage in the whole process to optimize the production of BC, which is a very important supplie in different fields of science such as: food, materials, water treatment, tissue engineering, etc. The optimization process was achieved with savings in production costs of the culture medium, through the reduction of glucose concentration by 75 % and through the reduction of the microorganism’s growth time.
Test-Retest Reliability of Task-based and Resting-state Blood Oxygen Level Dependence and Cerebral Blood Flow measures
Authors: Holiga Štefan , Sambataro Fabio , Luzy Cécile , Greig Gérard , Sarkar Neena , Renken Remco J , Marsman Jan-Bernard C , Schobel Scott A , Bertolino Alessandro , Dukart Juergen
Published: July 2018

Despite their wide-spread use, only limited information is available on the comparative test-retest reliability of task-based functional and resting state magnetic resonance imaging measures of blood oxygen level dependence (tb-fMRI and rs-fMRI) and cerebral blood flow (CBF) using arterial spin labeling. This information is critical to designing properly powered longitudinal studies. Here we comprehensively quantified and compared the test-retest reliability and reproducibility performance of 8 commonly applied fMRI tasks, 6 rs-fMRI metrics and CBF in 30 healthy volunteers. We find large variability in test-retest reliability performance across the different tb-fMRI paradigms and rs-fMRI metrics, ranging from poor to excellent. A larger extent of activation in tb-fMRI is linked to higher between-subject reliability of the respective task suggesting that differences in the amount of activation may be used as a first reliability estimate of novel tb-fMRI paradigms. For rs-fMRI, a good reliability of local activity estimates is paralleled by poor performance of global connectivity metrics. Evaluated CBF measures provide in general a good to excellent test-reliability matching or surpassing the best performing tb-fMRI and rs-fMRI metrics. This comprehensive effort allows for direct comparisons of test-retest reliability between the evaluated MRI domains and measures to aid the design of future tb-fMRI, rs-fMRI and CBF studies.
The BK channel gating ring is strongly coupled to the voltage sensor
Authors: Miranda Pablo , Holmgren Miguel , Giraldez Teresa
Published: July 2018

The open probability of large conductance voltage- and calcium-dependent potassium (BK) channels is regulated allosterically by changes in the transmembrane voltage and intracellular concentration of divalent ions (Ca2+ and Mg2+). The divalent cation sensors reside within the gating ring formed by eight Regulator of Conductance of Potassium (RCK) domains, two from each of the four channel subunits. Overall, the gating ring contains 12 sites that can bind Ca2+ with different affinities. Using patch-clamp fluorometry, we have shown robust changes in FRET signals within the gating ring in response to divalent ions and voltage, which do not directly track open probability. Only the conformational changes triggered through the RCK1 binding site are voltage-dependent in presence of Ca2+. Because the gating ring is outside the electric field, it must gain voltage sensitivity from coupling to the voltage-dependent channel opening, the voltage sensor or both. Here we demonstrate that alterations of voltage sensor dynamics known to shift gating currents produce a cognate shift in the gating ring voltage dependence, whereas changing BK channels’ relative probability of opening had little effect. These results strongly suggest that the conformational changes of the RCK1 domain of the gating ring are tightly coupled to the voltage sensor function, and this interaction is central to the allosteric modulation of BK channels.
Modelling bistable tumour population dynamics to design effective treatment strategies
Authors: Akhmetzhanov Andrei R. , Kim Jong Wook , Sullivan Ryan , Beckman Robert A. , Tamayo Pablo , Yeang Chen-Hsiang
Published: July 2018

Despite recent advances in targeted drugs and immunotherapy, cancer remains “the emperor of all maladies” due to inevitable emergence of resistance. Drug resistance is thought to be driven by mutations and/or dynamic plasticity that deregulate pathway activities and regulatory programs of a highly heterogeneous tumour. In this study, we propose a modelling framework to simulate population dynamics of heterogeneous tumour cells with reversible drug resistance. Drug sensitivity of a tumour cell is determined by its internal states, which are demarcated by coordinated activities of multiple interconnected oncogenic pathways. Transitions between cellular states depend on the effects of targeted drugs and regulatory relations between the pathways. Under this framework, we build a simple model to capture drug resistance characteristics of BRAF-mutant melanoma, where two cell states are described by two mutually inhibitory – main and alternative – pathways. We assume that cells with an activated main pathway are proliferative yet sensitive to the BRAF inhibitor, and cells with an activated alternative pathway are quiescent but resistant to the drug. We describe a dynamical process of tumour growth under various drug regimens using the explicit solution of mean-field equations. Based on these solutions, we compare efficacy of three treatment strategies: static treatments with continuous and constant dosages, periodic treatments with regular intermittent phases and drug holidays, and treatments derived from optimal control theory (OCT). Based on these analysis, periodic treatments outperform static treatments with a considerable margin, while treatments based on OCT outperform the best periodic treatment. Our results provide insights regarding optimal cancer treatment modalities for heterogeneous tumours, and may guide the development of optimal therapeutic strategies to circumvent drug resistance and due to tumour plasticity.