bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetic cooperativity in multi-layer networks implicates cell survival and senescence in the striatum of Huntington’s disease mice synchronous to symptoms
Authors: Bigan Erwan , Sasidharan Nair Satish , Lejeune François-Xavier , Fragnaud Hélissande , Parmentier Frédéric , Mégret Lucile , Verny Marc , Aaronson Jeff , Rosinski Jim , Neri Christian
Published: June 2019

Motivation

Huntington’s disease (HD) may evolve through gene deregulation. However, the impact of gene deregulation on the dynamics of genetic cooperativity in HD remains poorly understood. Here, we built a multi-layer network model of temporal dynamics of genetic cooperativity in the brain of HD knock-in mice (allelic series of Hdh mice). To enhance biological precision and gene prioritization, we integrated three complementary families of source networks, all inferred from the same RNA-seq time series data in Hdh mice, into weighted-edge networks where an edge recapitulates path-length variation across source-networks and age-points.

Results

Weighted edge networks identify two consecutive waves of tight genetic cooperativity enriched in deregulated genes (critical phases), pre-symptomatically in the cortex, implicating neurotransmission, and symptomatically in the striatum, implicating cell survival (e.g. Hipk4) intertwined with cell proliferation (e.g. Scn4b) and cellular senescence (e.g. Cdkn2a products) responses. Top striatal weighted edges are enriched in modulators of defective behavior in invertebrate models of HD pathogenesis, validating their relevance to neuronal dysfunction in vivo. Collectively, these findings reveal highly dynamic temporal features of genetic cooperativity in the brain of Hdh mice where a 2-step logic highlights the importance of cellular maintenance and senescence in the striatum of symptomatic mice, providing highly prioritized targets.

Availability and implementation

Weighted edge network analysis (WENA) data and source codes for performing spectral decomposition of the signal (SDS) and WENA analysis, both written using Python, are available at http://www.broca.inserm.fr/HD-WENA/.

Supplementary information

Supplementary data are available at Bioinformatics online.
Androgens regulate follicle stage-dependent pro- and anti-apoptosis in teleost ovaries through ZIP9 activation of different G proteins†
Authors: Converse Aubrey , Thomas Peter
Published: June 2019

Androgens mediate a number of processes in mammalian and teleost ovaries in a follicle-stage dependent manner, including follicle growth, survival, and apoptosis. We recently reported that the membrane androgen receptor ZIP9 mediates apoptosis in Atlantic croaker granulosa/theca (G/T) cells from mature ovarian follicles, but the effects of androgens on early stage G/T cells in this model remains unknown. Here we show that testosterone mediates pro- and anti-apoptotic responses in a follicle stage-dependent manner in croaker ovarian follicle cells. Testosterone treatment decreased the incidence of apoptosis in G/T cells from early stage follicles (diameter <300 μm) but increased apoptosis in G/T cells from late stage follicles (diameter >400 μm). Small interfering RNA targeting ZIP9, but not the nuclear androgen receptor, blocked the anti-apoptotic response, indicating ZIP9 mediates anti-apoptotic in addition to pro-apoptotic responses. Testosterone treatment of early stage G/T cells resulted in opposite signaling outcomes from those previously characterized for the ZIP9-mediated apoptotic response including decreased cAMP and intracellular free zinc levels, and downregulation of pro-apoptotic member mRNA expression. While ZIP9-mediated apoptosis involves activation of a stimulatory G protein (Gs), activators of Gs signaling antagonized the anti-apoptotic response. Proximity ligation and G protein activation assays indicated that in G/T cells from early stage follicles ZIP9 is in close proximity and activates an inhibitory G protein, while in G/T cells from late stage follicles ZIP9 is in close proximity and activates Gs. This study demonstrates that ZIP9 mediates opposite survival responses of croaker G/T cells by activating different G proteins in a follicle stage-dependent manner.
Nyap1 Regulates Multipolar–Bipolar Transition and Morphology of Migrating Neurons by Fyn Phosphorylation during Corticogenesis
Authors: Wang Shuzhong , Li Xuzhao , Zhang Qianru , Chai Xuejun , Wang Yi , Förster Eckart , Zhu Xiaoyan , Zhao Shanting
Published: June 2019

The coordination of cytoskeletal regulation is a prerequisite for proper neuronal migration during mammalian corticogenesis. Neuronal tyrosine-phosphorylated adaptor for the phosphoinositide 3-kinase 1 (Nyap1) is a member of the Nyap family of phosphoproteins, which has been studied in neuronal morphogenesis and is involved in remodeling of the actin cytoskeleton. However, the precise role of Nyap1 in neuronal migration remains unknown. Here, overexpression and knockdown of Nyap1 in the embryonic neocortex of mouse by in utero electroporation-induced abnormal morphologies and multipolar–bipolar transitions of migrating neurons. The level of phosphorylated Nyap1 was crucial for neuronal migration and morphogenesis in neurons. Furthermore, Nyap1 regulated neuronal migration as a downstream target of Fyn, a nonreceptor protein-tyrosine kinase that is a member of the Src family of kinases. Importantly, Nyap1 mediated the role of Fyn in the multipolar–bipolar transition of migrating neurons. Taken together, these results suggest that cortical radial migration is regulated by a molecular hierarchy of Fyn via Nyap1.
Potential for Point-of-Care Tests to Reduce Chlamydia-associated Burden in the United States: A Mathematical Modeling Analysis
Authors: Rönn Minttu M , Menzies Nicolas A , Gift Thomas L , Chesson Harrell W , Trikalinos Tom A , Bellerose Meghan , Malyuta Yelena , Berruti Andrés , Gaydos Charlotte A , Hsu Katherine K , Salomon Joshua A
Published: June 2019

Background

Point-of-care testing (POCT) assays for chlamydia are being developed. Their potential impact on the burden of chlamydial infection in the United States, in light of suboptimal screening coverage, remains unclear.

Methods

Using a transmission model calibrated to data in the United States, we estimated the impact of POCT on chlamydia prevalence, incidence, and chlamydia-attributable pelvic inflammatory disease (PID) incidence, assuming status quo (Analysis 1) and improved (Analysis 2) screening frequencies. We tested the robustness of results to changes in POCT sensitivity, the proportion of patients getting treated immediately, the baseline proportion lost to follow-up (LTFU), and the average treatment delay.

Results

In Analysis 1, high POCT sensitivity was needed to reduce the chlamydia-associated burden. With a POCT sensitivity of 90%, reductions from the baseline burden only occurred in scenarios in which over 60% of the screened individuals would get immediate treatment and the baseline LTFU proportion was 20%. With a POCT sensitivity of 99% (baseline LTFU 10%, 2-week treatment delay), if everyone were treated immediately, the prevalence reduction was estimated at 5.7% (95% credible interval [CrI] 3.9–8.2%). If only 30% of tested persons would wait for results, the prevalence reduction was only 1.6% (95% CrI 1.1–2.3). POCT with 99% sensitivity could avert up to 12 700 (95% CrI 5000–22 200) PID cases per year, if 100% were treated immediately (baseline LTFU 20% and 3-week treatment delay). In Analysis 2, when POCT was coupled with increasing screening coverage, reductions in the chlamydia burden could be realized with a POCT sensitivity of 90%.

Conclusions

POCT could improve chlamydia prevention efforts if test performance characteristics are significantly improved over currently available options.
Evaluation of a Redesigned Personal Protective Equipment Gown
Authors: Drews Frank A , Mulvey Diane , Stratford Kristina , Samore Matthew H , Mayer Jeanmarie
Published: June 2019

Background

In healthcare, the goal of personal protective equipment (PPE) is to protect healthcare personnel (HCP) and patients from body fluids and infectious organisms via contact, droplet, or airborne transmission. The critical importance of using PPE properly is highlighted by 2 potentially fatal viral infections, severe acute respiratory syndrome–associated coronavirus and Ebola virus, where HCP became infected while caring for patients due to errors in the use of PPE. However, PPE in dealing with less dangerous, but highly infectious organisms is important as well. This work proposes a framework to test and evaluate PPE with a focus on gown design.

Methods

An observational study identified issues with potential for contamination related to gown use. After redesigning the existing gown, a high-fidelity patient simulator study with 40 HCP as participants evaluated the gown redesign using 2 commonly performed tasks. Variables of interest were nonadherence to procedural standards, use problems with the gown during task performance, and usability and cognitive task load ratings of the standard and redesigned gowns.

Results

While no differences were found in terms of nonadherence and use problems between the current and the redesigned gown, differences in usability and task load ratings suggested that the redesigned gown is perceived more favorably by HCP.

Conclusions

This work proposes a framework to guide the evaluation of PPE. The results suggest that the current design of the PPE gown can be improved in usability and user satisfaction. Although our data did not find an increase in adherence to protocol when using the redesigned gown, it is likely that higher usability and lower task load could result in higher adherence over longer periods of use.
Transdiaphragmatic Mucormycosis
Authors: Koehler Philipp , Reimer Robert , Wahba Roger , Schömig-Markiefka Birgid , Cornely Oliver A
Published: June 2019

Mucormycosis is a life-threatening infection. This is the first report of transdiaphragmatic mucormycosis in a series of 3 patients. We observed this phenomenon in 11% of patients. Clinicians should be aware of this possibly underreported entity, and as a consequence we envision more comprehensive imaging studies in patients with mucormycosis.
Targeting protein tyrosine phosphatase PTP-PEST (PTPN12) for therapeutic intervention in acute myocardial infarction
Authors: Yang Chiu-Fen , Chen Yi-Yun , Singh Jai Prakash , Hsu Shu-Fang , Liu Yu-Wen , Yang Chun-Yi , Chang Chia-Wei , Chen Szu-Ni , Shih Rou-Ho , Hsu Shang-Te Danny , Jou Yuh-Shan , Cheng Ching-Feng , Meng Tzu-Ching
Published: June 2019

Aims

The myocardial ischaemia/reperfusion (I/R) injury is almost inevitable since reperfusion is the only established treatment for acute myocardial infarction (AMI). To date there is no effective strategy available for reducing the I/R injury. Our aim was to elucidate the mechanisms underlying myocardial I/R injury and to develop a new strategy for attenuating the damage it causes.

Methods and results

Using a mouse model established by ligation of left anterior descending artery, we found an increase in activity of protein tyrosine phosphatases (PTPs) in myocardium during I/R. Treating the I/R-mice with a pan-PTP inhibitor phenyl vinyl sulfone attenuated I/R damage, suggesting PTP activation to be harmful in I/R. Through analysing RNAseq data, we showed PTPs being abundantly expressed in mouse myocardium. By exposing primary cardiomyocytes ablated with specific endogenous PTPs by RNAi to hypoxia/reoxygenation (H/R), we found a role that PTP-PEST (PTPN12) plays to promote cell death under H/R stress. Auranofin, a drug being used in clinical practice for treating rheumatoid arthritis, may target PTP-PEST thus suppressing its activity. We elucidated the molecular basis for Auranofin-induced inactivation of PTP-PEST by structural studies, and then examined its effect on myocardial I/R injury. In the mice receiving Auranofin before reperfusion, myocardial PTP activity was suppressed, leading to restored phosphorylation of PTP-PEST substrates, including ErbB-2 that maintains the survival signalling of the heart. In line with the inhibition of PTP-PEST activity, the Auranofin-treated I/R-mice had smaller infarct size and better cardiac function.

Conclusions

PTP-PEST contributes to part of the damages resulting from myocardial I/R. The drug Auranofin, potentially acting through the PTP-PEST-ErbB-2 signalling axis, reduces myocardial I/R injury. Based on this finding, Auranofin could be used in the development of new treatments that manage I/R injury in patients with AMI.
Brugada syndrome in a young patient with type 1 myotonic dystrophy requiring an implantable cardioverter defibrillator for primary prevention: a case report
Authors: Korantzopoulos Panagiotis , Bechlioulis Aris , Lakkas Lampros , Naka Katerina K
Published: June 2019

Background 

Cardiac electrical disturbances represent the most frequent cardiac manifestations of myotonic dystrophy Type 1 (MD1). Limited data suggest that the prevalence of Brugada syndrome in MD1 may be increased compared to the general population.

Case summary 

We report a case of a 22-year-old asymptomatic man with repolarization abnormalities in leads V1–V3 suggestive of Type III Brugada pattern. The patient had a family history of MD and incidents of sudden death in relatives. Drug-induced Brugada Type 1 syndrome was revealed after procainamide challenge. A ventricular stimulation study was positive since a polymorphic ventricular tachycardia was induced after two extrastimuli. The patient underwent implantation of a single chamber cardiac defibrillator (ICD). Eight months after the procedure he suffered an appropriate ICD shock due to rapid polymorphic ventricular tachycardia.

Discussion 

Brugada syndrome is linked with MD1. Potential life-threatening arrhythmias may develop in the adult life of MD1 patients. Electrocardiographic surveillance and tailored invasive treatment with ICDs can prevent sudden cardiac death in this setting.
Oncolytic bacteria: past, present and future
Authors: Rius-Rocabert Sergio , Llinares Pinel Francisco , Pozuelo Maria Jose , García Antonia , Nistal-Villan Estanislao
Published: June 2019

More than a century ago, independent groups raised the possibility of using bacteria to selectively infect tumours. Such treatment induces an immune reaction that can cause tumour rejection and protect the patient against further recurrences. One of the first holistic approximations to use bacteria in cancer treatment was performed by William Coley, considered the father of immune-therapy, at the end of XIX century. Since then, many groups have used different bacteria to test their antitumour activity in animal models and patients. The basis for this reactivity implies that innate immune responses activated upon bacteria recognition, also react against the tumour. Different publications have addressed several aspects of oncolytic bacteria. In the present review, we will focus on revisiting the historical aspects using bacteria as oncolytic agents and how they led to the current clinical trials. In addition, we address the molecules present in oncolytic bacteria that induce specific toxic effects against the tumors as well as the activation of host immune responses in order to trigger antitumour immunity. Finally, we discuss future perspectives that could be considered in the different fields implicated in the implementation of this kind of therapy in order to improve the current use of bacteria as oncolytic agents.
Genetic Variation in Human Gene Regulatory Factors Uncovers Regulatory Roles in Local Adaptation and Disease
Authors: Perdomo-Sabogal Álvaro , Nowick Katja
Published: June 2019

Differences in gene regulation have been suggested to play essential roles in the evolution of phenotypic changes. Although DNA changes in cis-regulatory elements affect only the regulation of its corresponding gene, variations in gene regulatory factors (trans) can have a broader effect, because the expression of many target genes might be affected. Aiming to better understand how natural selection may have shaped the diversity of gene regulatory factors in human, we assembled a catalog of all proteins involved in controlling gene expression. We found that at least five DNA-binding transcription factor classes are enriched among genes located in candidate regions for selection, suggesting that they might be relevant for understanding regulatory mechanisms involved in human local adaptation. The class of KRAB-ZNFs, zinc-finger (ZNF) genes with a Krüppel-associated box, stands out by first, having the most genes located on candidate regions for positive selection. Second, displaying most nonsynonymous single nucleotide polymorphisms (SNPs) with high genetic differentiation between populations within these regions. Third, having 27 KRAB-ZNF gene clusters with high extended haplotype homozygosity. Our further characterization of nonsynonymous SNPs in ZNF genes located within candidate regions for selection, suggests regulatory modifications that might influence the expression of target genes at population level. Our detailed investigation of three candidate regions revealed possible explanations for how SNPs may influence the prevalence of schizophrenia, eye development, and fertility in humans, among other phenotypes. The genetic variation we characterized here may be responsible for subtle to rough regulatory changes that could be important for understanding human adaptation.
Multimorbidity and Cognitive Decline Over 14 Years in Older Americans
Authors: Wei Melissa Y , Levine Deborah A , Zahodne Laura B , Kabeto Mohammed U , Langa Kenneth M
Published: June 2019

Background

Multimorbidity is associated with greater disability and accelerated declines in physical functioning over time in older adults. However, less is known about its effect on cognitive decline.

Methods

Participants without dementia from the Health and Retirement Study were interviewed about physician-diagnosed conditions, from which their multimorbidity-weighted index (MWI) that weights diseases to physical functioning was computed. We used linear mixed-effects models to examine the predictor MWI with the modified Telephone Interview for Cognitive Status (TICSm, global cognition), 10-word immediate recall and delayed recall, and serial 7s outcomes biennially after adjusting for baseline cognition and covariates.

Results

Fourteen thousand two hundred sixty-five participants, 60% female, contributed 73,700 observations. Participants had a mean ± SD age 67 ± 9.3 years and MWI 4.4 ± 3.9 at baseline. Each point increase in MWI was associated with declines in global cognition (0.04, 95% CI: 0.03–0.04 TICSm), immediate recall (0.01, 95% CI: 0.01–0.02 words), delayed recall (0.01, 95% CI: 0.01–0.02 words), and working memory (0.01, 95% CI: 0.01–0.02 serial 7s; all p < .001). Multimorbidity was associated with faster declines in global cognition (0.003 points/year faster, 95% CI: 0.002–0.004), immediate recall (0.001 words/year faster, 95% CI: 0.001–0.002), and working memory (0.006 incorrect serial 7s/year faster, 95% CI: 0.004–0.009; all p < .001), but not delayed recall compared with premorbid slopes.

Conclusions

Multimorbidity using a validated index weighted to physical functioning was associated with acute decline in cognition and accelerated and persistent cognitive decline over 14 years. This study supports an ongoing geriatric syndrome of coexisting physical and cognitive impairment in adults with multimorbidity. Clinicians should monitor and address both domains in older multimorbid adults.
The Effect of Initiation of Anti-TNF Therapy on the Subsequent Direct Health Care Costs of Inflammatory Bowel Disease
Authors: Targownik Laura E , Benchimol Eric I , Witt Julia , Bernstein Charles N , Singh Harminder , Lix Lisa , Tennakoon Aruni , Zubieta Antonio Aviña , Coward Stephanie , Jones Jennifer , Kuenzig Ellen , Murthy Sanjay K , Nguyen Geoffrey C , Peña-Sánchez Juan Nicolás , Kaplan Gil
Published: June 2019

Background

Anti–tumor necrosis factor (anti-TNF) drugs are highly effective in the treatment of moderate-to-severe Crohn’s disease (CD) and ulcerative colitis (UC), but they are very costly. Due to their effectiveness, they could potentially reduce future health care spending on other medical therapies, hospitalization, and surgery. The impact of downstream costs has not previously been quantified in a real-world population-based setting.

Methods

We used the University of Manitoba IBD Database to identify all persons in a Canadian province with CD or UC who received anti-TNF therapy between 2004 and 2016. All inpatient, outpatient, and drug costs were enumerated both in the year before anti-TNF initiation and for up to 5 years after anti-TNF initiation. Costs before and after anti-TNF initiation were compared, and multivariate linear regression analyses were performed to look for predictors of higher costs after anti-TNF initiation.

Results

A total of 928 people with IBD (676 CD, 252 UC) were included for analyses. The median cost of health care in the year before anti-TNF therapy was $4698 for CD vs $6364 for UC. The median cost rose to $39,749 and $49,327, respectively, in the year after anti-TNF initiation, and to $210,956 and $245,260 in the 5 years after initiation for continuous anti-TNF users. Inpatient and outpatient costs decreased in the year after anti-TNF initiation by 12% and 7%, respectively, when excluding the cost of anti-TNFs.

Conclusions

Direct health care expenditures markedly increase after anti-TNF initiation and continue to stay elevated over pre-initiation costs for up to 5 years, with only small reductions in the direct costs of non-drug-related health care.
The role of the non-indigenous green crab (Carcinus maenas) in the decline of a unique strain of Irish moss (Chondrus crispus): direct and indirect effects
Authors: Tummon Flynn Paula , Lynn Kassandra Devon , Cairns David K , Quijón Pedro A
Published: June 2019

A unique strain of the red alga Irish moss (Chondrus crispus) is found solely amongst clumps of blue mussels (Mytilus edulis) in a coastal lagoon in Atlantic Canada. Since about 2000, its bed area has shrunk by >99.9%, coinciding with the arrival of the non-indigenous green crab (Carcinus maenas). This study tested two mechanisms by which green crabs may harm the Irish moss. The hypothesis that green crabs directly consume the alga was tested by exposing fronds and clumps to crabs. Crab interaction with the clumps caused limited fragmentation, consumption was very small, and the condition (visible grazing damage) of fronds did not change significantly. A second hypothesis, that during predation and handling of mussels green crabs indirectly displace the seaweed and remove its attachment substrate, was addressed by placing crabs with Irish moss-mussel clumps containing either large or small mussels. Green crabs removed and ate up to 100% of the small mussels but did not consume or displace large mussels. This study concludes that direct consumption is not a plausible mechanism for green crabs to harm this strain. Instead, green crabs harm could be mediated by mussels, whose removal deprives the giant Irish moss of positional stability.
Residential distance from high-voltage overhead power lines and risk of Alzheimer’s dementia and Parkinson’s disease: a population-based case-control study in a metropolitan area of Northern Italy
Authors: Gervasi Federico , Murtas Rossella , Decarli Adriano , Russo Antonio Giampiero
Published: June 2019

Background

The association between the extremely low-frequency magnetic field generated by overhead power lines and neurodegenerative disease is still a matter of debate.

Methods

A population-based case-control study was carried out on the residents in the Milan metropolitan area between 2011 and 2016 to evaluate the possible association between exposure to extremely low-frequency magnetic fields generated by high-voltage overhead power lines and Alzheimer's dementia and Parkinson's disease. A statistical analysis was performed on cases and controls matched by sex, year of birth and municipality of residence (with a case to controls ratio of 1 : 4) using conditional logistic regression models adjusted for socio-economic deprivation and distance from the major road network as potential confounders.

Results

Odds ratios for residents <50 m from the source of exposure compared with residents at ≥600 m turned out to be 1.11 (95% confidence interval: 0.95–1.30) for Alzheimer's dementia and 1.09 (95% confidence interval: 0.92–1.30) for Parkinson's disease.

Conclusions

The finding of a weak association between exposure to the extremely low-frequency magnetic field and neurodegenerative diseases suggests the continuation of research on this topic. Moreover, the low consistency between the results of the already existing studies emphasises the importance of increasingly refined study designs.
How Issue Salience Explains the Rise of the Populist Right in Western Europe
Authors: Dennison James
Published: June 2019

This article tests whether variation in issue salience can explain the rise of the populist right in Western Europe. By taking a novel cross-country and cross-time approach at both the aggregate- and individual levels using panel data, I robustly demonstrate that the salience of immigration positively affects electoral support for the populist right. I also find, using a structural equation modeling approach, that the salience of immigration, in turn, is partially caused by immigration rates. I do not find evidence of a positive effect of the salience of the issues of crime, unemployment, the economy, or terrorism. I find evidence of a positive effect of the salience of Europe at the individual level, which is of a similar scale to immigration.
When Less Is More: Sex Ratios for the Mass-Rearing of Anastrepha ludens (Diptera: Tephritidae)
Authors: González-López G I , Solís-Echeverría E , Díaz-Fleischer F , Pérez-Staples D
Published: June 2019

Anastrepha ludens (Loew) is one of the most important pests of citrus and mango crops in Mexico. A method used to control this pest is the sterile insect technique, which consists in the mass production, irradiation, and release of insects in affected areas. The production of insects begins with the establishment of colonies to produce eggs, which must be highly fertile to ensure an adequate production of larvae. However, female fecundity and fertility can be affected by adult density and sex ratio, thus an optimal sex ratio in mass-rearing cages must be used. The genetic sexing strain of A. ludens (Tapachula-7) allows the identification of the sex at the pupal stage, making it possible to establish rearing cages with different sex ratios. We determined if different sex ratios have an effect on egg production. Two sex ratios (4♀: 1♂ and 1♀: 1♂) were compared. Fecundity, fertility and survival at different ages were also determined. Higher fertility and fecundity per female were observed at a ratio of 4:1. However, females with higher fecundity had reduced survival probabilities. In conclusion, maintaining colonies with a lower proportion of males in cages ensures a greater fecundity and fertility. Further research is necessary to understand whether results can be attributed to lower male harassment in cages.
Montagu Burrows and the Generational Anxieties of a Victorian Historian
Authors: Garritzen Elise
Published: June 2019

The generation-consciousness of Montagu Burrows (1819–1905), first a naval officer and later Chichele Professor of Modern History in Oxford, illustrates how Victorians located themselves at the juncture of biological and socially constructed historical generations and had overlapping and conflicting generational affiliations. As a historian Burrows believed in progress: the flow of generations connected past, present, and future, and each generation advanced to a higher position. As a professor, Burrows was marginalized and this essay suggests that generational affinities played a role in this. Spending his adolescence at sea, he missed out the vital formative experience of early Oxford education. By adopting the romantic ideal of a historian as a moral guide he cultivated the persona of an instructor rather than a researcher. This persona, embraced by earlier generations, appeared antiquated to Burrows’s near contemporaries who endeavoured to make history a research-based discipline. By exploring how Burrows negotiated the generational belonging and unbelonging he experienced as an historian, this essay shows that generation could function as an important category of inclusion and exclusion for professional communities.
Whole genome sequence of first Candida auris strain, isolated in Russia
Authors: Pchelin Ivan M , Azarov Daniil V , Churina Maria A , Ryabinin Igor A , Vibornova Irina V , Apalko Svetlana V , Kruglov Alexander N , Sarana Andrey M , Taraskina Anastasia E , Vasilyeva Natalya V
Published: June 2019

Candida auris is an emergent yeast pathogen, easily transmissible between patients and with high percent of multidrug resistant strains. Here we present a draft genome sequence of the first known Russian strain of C. auris, isolated from a case of candidemia. The strain clustered within South Asian C. auris clade and seemingly represented an independent event of dissemination from the original species range. Observed fluconazole resistance was probably due to F105L and K143R mutations in ERG11.
The galaxy–halo connection in modified gravity cosmologies: environment dependence of galaxy luminosity function
Authors: Devi N Chandrachani , Rodríguez-Puebla Aldo , Valenzuela O , Avila-Reese Vladimir , Hernández-Aguayo César , Li Baojiu
Published: June 2019

We investigate the dependence of the galaxy–halo connection and galaxy density field in modified gravity models using the N-body simulations for f(R) and nDGP models at z = 0. Because of the screening mechanisms employed by these models, chameleon and Vainshtein, haloes are clustered differently in the non-linear regime of structure formation. We quantify their deviations in the galaxy density field from the standard Λ cold dark matter (ΛCDM) model under different environments. We populate galaxies in haloes via the (sub)halo abundance matching. Our main results are as follows: (1) The galaxy–halo connection strongly depends on the gravity model; a maximum variation of ${\sim }40{{\ \rm per\ cent}}$ is observed between halo occupational distribution (HOD) parameters; (2) f(R) gravity models predict an excess of galaxies in low-density environments of ${\sim }10{{\ \rm per\ cent}}$ but predict a deficit of ${\sim }10{{\ \rm per\ cent}}$ at high-density environments for |fR0| = 10−4 and 10−6 while |fR0| = 10−5 predicts more high-density structures; nDGP models are consistent with ΛCDM; (3) different gravity models predict different dependences of the galaxy luminosity function (GLF) with the environment, especially in void-like regions we find differences around ${\sim }10{{\ \rm per\ cent}}$ for the f(R) models while nDPG models remain closer to ΛCDM for low-luminosity galaxies but there is a deficit of ${\sim }11{{\ \rm per\ cent}}$ for high-luminosity galaxies in all environments. We conclude that the dependence of the GLF with environment might provide a test to distinguish between gravity models and their screening mechanisms from the ΛCDM. We provide HOD parameters for the gravity models analysed in this paper.
On the radio image of relativistic jets – I. Internal structure, Doppler boosting, and polarization maps
Authors: Chernoglazov A V , Beskin V S , Pariev V I
Published: June 2019

In this first paper from forthcoming series of works devoted to radio image of relativistic jets from active galactic nuclei the role of internal structure of a flow is discussed. We determine the radial profiles of all physical values for reasonable Michel magnetization parameter σM and ambient pressure Pext. Maps of Doppler boosting factor δ and observed directions of linear polarization of synchrotron emission are also constructed.
NIHAO – XXII. Introducing black hole formation, accretion, and feedback into the NIHAO simulation suite
Authors: Blank Marvin , Macciò Andrea V , Dutton Aaron A , Obreja Aura
Published: June 2019

We introduce algorithms for black hole physics, i.e. black hole formation, accretion, and feedback, into the Numerical Investigation of a Hundred Astrophysical Objects (NIHAO) project of galaxy simulations. This enables us to study high mass, elliptical galaxies, where feedback from the central black hole is generally thought to have a significant effect on their evolution. We furthermore extend the NIHAO suite by 45 simulations that encompass z = 0 halo masses from 1 × 1012 to $4 \times 10^{13}\, \mathrm{M}_{\odot }$, and resimulate five galaxies from the original NIHAO sample with black hole physics, which have z = 0 halo masses from 8 × 1011 to $3 \times 10^{12}\, \mathrm{M}_{\odot }$. Now NIHAO contains 144 different galaxies and thus has the largest sample of zoom-in simulations of galaxies, spanning z = 0 halo masses from 9 × 108 to $4 \times 10^{13}\, \mathrm{M}_{\odot }$. In this paper we focus on testing the algorithms and calibrating their free parameters against the stellar mass versus halo mass relation and the black hole mass versus stellar mass relation. We also investigate the scatter of these relations, which we find is a decreasing function with time and thus in agreement with observations. For our fiducial choice of parameters we successfully quench star formation in objects above a z = 0 halo mass of $10^{12}\, \mathrm{M}_{\odot }$, thus transforming them into red and dead galaxies.
Bayesian hierarchical inference of asteroseismic inclination angles
Authors: Kuszlewicz James S , Chaplin William J , North Thomas S H , Farr Will M , Bell Keaton J , Davies Guy R , Campante Tiago L , Hekker Saskia
Published: June 2019

The stellar inclination angle – the angle between the rotation axis of a star and our line of sight – provides valuable information in many different areas, from the characterization of the geometry of exoplanetary and eclipsing binary systems to the formation and evolution of those systems. We propose a method based on asteroseismology and a Bayesian hierarchical scheme for extracting the inclination angle of a single star. This hierarchical method therefore provides a means to both accurately and robustly extract inclination angles from red giant stars. We successfully apply this technique to an artificial data set with an underlying isotropic inclination angle distribution to verify the method. We also apply this technique to 123 red giant stars observed with Kepler. We also show the need for a selection function to account for possible population-level biases, which are not present in individual star-by-star cases, in order to extend the hierarchical method towards inferring underlying population inclination angle distributions.
The build-up of pseudo-bulges in a hierarchical universe
Authors: Izquierdo-Villalba David , Bonoli Silvia , Spinoso Daniele , Rosas-Guevara Yetli , Henriques Bruno M B , Hernández-Monteagudo Carlos
Published: June 2019

We study the cosmological build-up of pseudo-bulges using the L-Galaxies semi-analytical model for galaxy formation with a new approach for following separately the assembly of classical bulges and pseudo-bulges. Classical bulges are assumed to be the result of violent processes (i.e. mergers and starbursts), while the formation of pseudo-bulges is connected to the secular growth of discs. We apply the model to both the Millennium and the Millennium II simulations, in order to study our results across a wide range of stellar masses ($\rm 10^{7}\!-\!10^{11.5}\, {\rm M}_{\odot }$). We find that z = 0 pseudo-bulges mainly reside in galaxies of $\mathit{ M}_{\rm stellar} \, {\sim }\, 10^{10}\!-\!10^{10.5}\, {\rm M}_{\odot }$ ($\mathit{ M}_{\rm halo} \, {\sim }\, 10^{11.5}\!-\!10^{12}\, {\rm M}_{\odot }$) and we recover structural properties of these objects (e.g. sizes and bulge-to-total ratios) that are in good agreement with observational results. Tracing their formation history, we find that pseudo-bulges assembled in galaxies with a very quiet merger history, as opposed to the host galaxies of classical bulges. Regarding the bulge structure, we find that $\, {\sim }\, 30{{\ \rm per\ cent}}$ of the galaxies with a predominant pseudo-bulge feature a composite structure, hosting both a pseudo- and a classical bulge component. The classical component typically constitutes ${\sim }\, 10{{\ \rm per\ cent}}$ of the total bulge galaxy mass. When looking at the properties of the host galaxies, we find that z = 0 pseudo-bulges are hosted by main-sequence galaxies, characterized by a stellar population which is generally younger compared to the one of the hosts of classical bulges.
A general approach to quenching and galactic conformity
Authors: Sin Larry P T , Lilly Simon J , Henriques Bruno M B
Published: June 2019

We develop a conceptual framework and methodology to study the drivers of the quenching of galaxies, including the drivers of galactic conformity. The framework is centred on the statistic Δ, which is defined as the difference between the observed star formation state of a galaxy, and a prediction of its state based on an empirical model of quenching. In particular, this work uses the average quenching effects of stellar mass M* and local density δ to construct an empirical model of quenching. Δ is therefore a residual which reflects the effects of drivers of quenching not captured by M* and δ, or so-called hidden variables. Through a toy model, we explore how the statistical properties of Δ can be used to learn about the internal and external hidden variables which control the quenching of a sample of galaxies. We then apply this analysis to a sample of local galaxies and find that, after accounting for the average quenching effects of M* and δ, Δ remains correlated out to separations of 3 Mpc. Furthermore, we find that external hidden variables remain important for driving the residual quenching of low-mass galaxies, while the residual quenching of high-mass galaxies is driven mostly by internal properties. These results, along with a similar analysis of a semi-analytical mock catalogue, suggest that it is necessary to consider halo-related properties as candidates for hidden variables. A preliminary halo-based analysis indicates that much of the correlation of Δ can be attributed to the physics associated with individual haloes.
DNMT3B shapes the mCA landscape and regulates mCG for promoter bivalency in human embryonic stem cells
Authors: Tan Hong Kee , Wu Chan-Shuo , Li Jia , Tan Zi Hui , Hoffman Jordan R , Fry Christopher J , Yang Henry , Di Ruscio Annalisa , Tenen Daniel G
Published: June 2019

DNMT3B is known as a de novo DNA methyltransferase. However, its preferential target sites for DNA methylation are largely unknown. Our analysis on ChIP-seq experiment in human embryonic stem cells (hESC) revealed that DNMT3B, mCA and H3K36me3 share the same genomic distribution profile. Deletion of DNMT3B or its histone-interacting domain (PWWP) demolished mCA in hESCs, suggesting that PWWP domain of DNMT3B directs the formation of mCA landscape. In contrast to the common presumption that PWWP guides DNMT3B-mediated mCG deposition, we found that deleting PWWP does not affect the mCG landscape. Nonetheless, DNMT3B knockout led to the formation of 2985 de novo hypomethylated regions at annotated promoter sites. Upon knockout, most of these promoters gain the bivalent marks, H3K4me3 and H3K27me3. We call them spurious bivalent promoters. Gene ontology analysis associated spurious bivalent promoters with development and cell differentiation. Overall, we found the importance of DNMT3B for shaping the mCA landscape and for maintaining the fidelity of the bivalent promoters in hESCs.
Germline genetic landscape of pediatric central nervous system tumors
Authors: Muskens Ivo S , Zhang Chenan , de Smith Adam J , Biegel Jaclyn A , Walsh Kyle M , Wiemels Joseph L
Published: June 2019

Central nervous system (CNS) tumors are the second most common type of cancer among children. Depending on histopathology, anatomic location, and genomic factors, specific subgroups of brain tumors have some of the highest cancer-related mortality rates or result in considerable lifelong morbidity. Pediatric CNS tumors often occur in patients with genetic predisposition, at times revealing underlying cancer predisposition syndromes. Advances in next-generation sequencing (NGS) have resulted in the identification of an increasing number of cancer predisposition genes. In this review, the literature on genetic predisposition to pediatric CNS tumors is evaluated with a discussion of potential future targets for NGS and clinical implications. Furthermore, we explore potential strategies for enhancing the understanding of genetic predisposition of pediatric CNS tumors, including evaluation of non-European populations, pan-genomic approaches, and large collaborative studies.
Congress of Neurological Surgeons Systematic Review and Evidence-Based Guideline on the Management of Patients With Myelomeningocele: Whether Prenatal or Postnatal Closure Affects Future Ambulatory Status
Authors: Bauer David F , Beier Alexandra D , Nikas Dimitrios C , Assassi Nadege , Blount Jeffrey , Durham Susan R , Flannery Ann Marie , Klimo Jr Paul , McClung-Smith Catherine , Rehring Patricia , Tamber Mandeep S , Tyagi Rachana , Mazzola Catherine A
Published: June 2019

BACKGROUND

Myelomeningocele (MM) is an open neural tube defect treated by pediatric neurosurgeons with prenatal or postnatal closure.

OBJECTIVE

The objective of this systematic review was to answer the question: What is the evidence for the effectiveness of prenatal vs postnatal closure of MM regarding short and long-term ambulatory status? Treatment recommendations were provided based on the available evidence.

METHODS

The National Library of Medicine PubMed database and Embase were queried using MeSH headings and keywords relevant to ambulatory status after prenatal or postnatal closure of MM. Abstracts were reviewed to identify which studies met the inclusion criteria. An evidence table was assembled summarizing the studies and the quality of evidence (Classes I-III). Based on the quality of the literature, a recommendation was rendered (Level I, II, or III).

RESULTS

One randomized controlled trial (Class II) and 3 retrospective cohort studies (Class III) were included as evidence. Initial ambulatory status depended on anatomic level of the neural tube defect. In the short term, prenatal closure may improve ambulatory status compared to postnatal closure. Spinal cord tethering or dermoid inclusion cyst has been associated with neurologic deterioration in infants closed in utero and after birth. Ambulation may cease in both groups over time. No long-term studies evaluated whether there is a difference in the ability to ambulate upon reaching adulthood.

CONCLUSION

Prenatal closure of MM may improve ambulatory status in the short term (Level II). Spinal cord tethering in both groups caused deterioration in the ability to walk. Evaluation and treatment of spinal cord tethering may help maintain ambulatory status (Level III). No studies evaluate whether prenatal or postnatal repair provides improved ability to ambulate upon reaching adulthood.

The full guideline can be found at https://www.cns.org/guidelines/guidelines-spina-bifida-chapter-3.
The Myth of Flexible Universality: Human Rights and the Limits of Comparative Naturalism
Authors: Heinze Eric
Published: June 2019

Many writers reject the notion of universal human rights, insisting on their historically recent, Western-secular character. Other theorists emphasise mutual exchange between human rights and systems such as Confucianism, Buddhism and Islam. They celebrate a common ground that would appear, moreover, to enhance the case for universality. This article acknowledges that common ground but rejects the view that it can strengthen the case for universality. Any such ‘exchange’, far from being mutual, turns out to be dictated entirely by human rights. Familiar rhetoric about the supposed flexibility of human rights law, which would suggest genuinely interactive relationships between it and other belief systems, flatly contradicts its higher-law claims. Genuinely flexible human rights could only ever arise either (i) in the trivial sense that any broadly formulated legal rule ends up applied to a range of situations or (ii) in the untenable sense that human rights law would accommodate serious violations.
Involvement of HD-ZIP I transcription factors LcHB2 and LcHB3 in fruitlet abscission by promoting transcription of genes related to the biosynthesis of ethylene and ABA in litchi
Authors: Ma Xingshuai , Li Caiqin , Huang Xuming , Wang Huicong , Wu Hong , Zhao Minglei , Li Jianguo
Published: June 2019

Abnormal fruitlet abscission is a limiting factor in the production of litchi, an economically important fruit in Southern Asia. Both ethylene and abscisic acid (ABA) induce organ abscission in plants. Although ACS/ACO and NCED genes are known to encode key enzymes required for ethylene and ABA biosynthesis, respectively, the transcriptional regulation of these genes is unclear in the process of plant organ shedding. Here, two polygalacturonase (PG) genes (LcPG1 and LcPG2) and two novel homeodomain-leucine zipper I transcription factors genes (LcHB2 and LcHB3) were identified as key genes associated with the fruitlet abscission in litchi. The expression of LcPG1 and LcPG2 was strongly associated with litchi fruitlet abscission, consistent with enhanced PG activity and reduced homogalacturonan content in fruitlet abscission zones (FAZs). The promoter activities of LcPG1/2 were enhanced by ethephon and ABA. In addition, the production of ethylene and ABA in fruitlets was significantly increased during fruit abscission. Consistently, expression of five genes (LcACO2, LcACO3, LcACS1, LcACS4 and LcACS7) related to ethylene biosynthesis and one gene (LcNCED3) related to ABA biosynthesis in FAZs were activated. Further, electrophoretic mobility shift assays and transient expression experiments demonstrated that both LcHB2 and LcHB3 could directly bind to the promoter of LcACO2/3, LcACS1/4/7 and LcNCED3 genes and activate their expression. Collectively, we propose that LcHB2/3 are involved in the litchi fruitlet abscission through positive regulation of ethylene and ABA biosynthesis.
Homoplasy and extinction: the phylogeny of cassidulid echinoids (Echinodermata)
Authors: Souto Camilla , Mooi Rich , Martins Luciana , Menegola Carla , Marshall Charles R
Published: June 2019

Inclusion of fossils can be crucial to address evolutionary questions, because their unique morphology, often drastically modified in recent species, can improve phylogenetic resolution. We performed a cladistic analysis of 45 cassidulids with 98 characters, which resulted in 24 most parsimonious trees. The strict consensus recovers three major cassiduloid clades, and the monophyly of the family Cassidulidae is not supported. Ancillary analyses to determine the sensitivity of the phylogeny to missing data do not result in significantly different topologies. The taxonomic implications of these results, including the description of a new cassiduloid family and the evolution of some morphological features, are discussed. Cassiduloids (as defined here) most probably originated in the Early Cretaceous, and their evolutionary history has been dominated by high levels of homoplasy and a dearth of unique, novel traits. Despite their high diversity during the Palaeogene, there are only seven extant cassiduloid species, and three of these are relicts of lineages dating back to the Eocene. Future studies of the biology of these poorly known species, some of which brood their young, will yield further insights into the evolutionary history of this group.
NPs' use of guidelines to diagnose and treat childhood ADHD
Authors: Jansen Mashelle
Published: June 2019

Current research on NPs' use of the American Academy of Pediatrics (AAP) Clinical Practice Guideline for the Diagnosis, Evaluation, and Treatment of Attention-Deficit/Hyperactivity Disorder in Children and Adolescents is limited. This cross-sectional survey examined 89 NPs in Upstate New York regarding self-reported practice behaviors based on the guideline. Most NPs followed at least 50% of the AAP guideline for diagnosis and treatment. However, use of all criteria was less than optimal.