bluuebunny/crossref_metadata_2025 huggingface dataset:
Genotypic diversity and genotype identity of resident species drive community composition
Authors: Hadincová Věroslava , Skálová Hana , Münzbergová Zuzana
Published: January 2020

Aims

Species-rich plant communities are more resistant to invasions. In the past decade it was demonstrated that genetic variation also has many ecological effects. In our study we aimed to test whether the patterns of response to the genetic diversity of a resident species differ between colonizing species of different growth forms and whether the response is affected by soil nutrients.

Methods

We established experimental stands of a common grass, Festuca rubra, harbouring three levels of genetic diversity (1, 6 or 18 clonal genotypes, referred to as genotypic diversity) under two soil nutrient levels. In the fourth year after the stands were established, we sowed a mixture of four colonizers into the stands: a stoloniferous legume (Trifolium repens), a broad-leaf tussock grass (Anthoxanthum odoratum), a large-rosette forb (Plantago lanceolata) and a small-rosette forb (Campanula rotundifolia). We observed species establishment and growth over 3 years. We tested whether colonization success depended on genotypic diversity, specific Festuca genotypes, soil nutrients and colonizer growth form.

Important Findings

The colonization success and biomass of the colonizers were significantly affected by the genotypic diversity and the genotype identity of the resident clonal grass. The response, however, differed between the colonizers. The strongest response to the genotypic diversity of the resident species was observed in the tussock grass with a growth form and architecture similar to the resident species. The large-rosette species responded in early stages of growth whereas the stoloniferous legume did not respond at all. The intraspecific genotypic diversity and genotype identity of the resident species play an important role in the assembly of plant communities.
Absorbed radiation doses in the thyroid as estimated by UNSCEAR and subsequent risk of childhood thyroid cancer following the Great East Japan Earthquake
Authors: Ohira Tetsuya , Shimura Hiroki , Hayashi Fumikazu , Nagao Masanori , Yasumura Seiji , Takahashi Hideto , Suzuki Satoru , Matsuzuka Takashi , Suzuki Satoshi , Iwadate Manabu , Ishikawa Tetsuo , Sakai Akira , Suzuki Shinichi , Nollet Kenneth E , Yokoya Susumu , Ohto Hitoshi , Kamiya Kenji ,   for the Fukushima Health Management Survey Group
Published: January 2020

The identification of thyroid cancers among children after the Chernobyl nuclear power plant accident propelled concerns regarding long-term radiation effects on thyroid cancer in children affected by the Fukushima Daiichi nuclear power plant accident in Fukushima, Japan. Herein we consider the potential association between absorbed dose in the thyroid and the risk of developing thyroid cancer as detected by ultrasonography on 300 473 children and adolescents aged 0–18 years in Fukushima. The absorbed dose mentioned in the present study indicates the sum of that from external exposure and that from internally deposited radionuclides. We grouped participants according to estimated absorbed doses in each of 59 municipalities in Fukushima Prefecture, based on The United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR) 2013 report. The 59 municipalities were assigned to quartiles by dose. We limited our analyses to participants aged ≥6 years because only one case of thyroid cancer was observed in participants aged ≤5 years; 164 299 participants were included in the final analysis. Compared with the lowest dose quartile, the age- and sex-adjusted rate ratios (95% confidence intervals) for the low-middle, high-middle and highest quartiles were 2.00 (0.84–4.80), 1.34 (0.50–3.59) and 1.42 (0.55–3.67) for the 6–14-year-old groups and 1.99 (0.70–5.70), 0.54 (0.13–2.31) and 0.51 (0.12–2.15) for the >15-year-old group, respectively. No dose-dependent pattern emerged from the geographical distribution of absorbed doses by municipality, as estimated by UNSCEAR, and the detection of thyroid cancer among participants within 4–6 years after the accident. Ongoing surveillance might further clarify the effects of low-dose radiation exposure on thyroid cancer in Fukushima.
Disc tearing and Bardeen–Petterson alignment in GRMHD simulations of highly tilted thin accretion discs
Authors: Liska M , Hesp C , Tchekhovskoy A , Ingram A , van der Klis M , Markoff S B , Van Moer M
Published: January 2020

Luminous active galactic nuclei and X-ray binaries often contain geometrically thin, radiatively cooled accretion discs. According to theory, these are – in many cases – initially highly misaligned with the black hole equator. In this work, we present the first general relativistic magnetohydrodynamic simulations of very thin (h/r ∼ 0.015–0.05) accretion discs around rapidly spinning (a ∼ 0.9) black holes and tilted by 45°–65°. We show that the inner regions of the discs with h/r ≲ 0.03 align with the black hole equator, though out to smaller radii than predicted by analytic work. The inner aligned and outer misaligned disc regions are separated by a sharp break in tilt angle accompanied by a sharp drop in density. We find that frame dragging by the spinning black hole overpowers the disc viscosity, which is self-consistently produced by magnetized turbulence, tearing the disc apart and forming a rapidly precessing inner sub-disc surrounded by a slowly precessing outer sub-disc. We find that the system produces a pair of relativistic jets for all initial tilt values. At small distances, the black hole launched jets precess rapidly together with the inner sub-disc, whereas at large distances they partially align with the outer sub-disc and precess more slowly. If the tearing radius can be modeled accurately in future work, emission model independent measurements of black hole spin based on precession-driven quasi-periodic oscillations may become possible.
Towards determining the neutrino mass hierarchy: weak lensing and galaxy clustering forecasts with baryons and intrinsic alignments
Authors: Copeland David , Taylor Andy , Hall Alex
Published: January 2020

The capacity of Stage IV lensing surveys to measure the neutrino mass sum and differentiate between the normal and inverted mass hierarchies depends on the impact of nuisance parameters describing small-scale baryonic astrophysics and intrinsic alignments. For a Euclid-like survey, we perform the first combined weak lensing and galaxy clustering Fisher analysis with baryons, intrinsic alignments, and massive neutrinos for both hierarchies. We use a matter power spectrum generated from a halo model that captures the impact of baryonic feedback and adiabatic contraction. For weak lensing, we find that baryons cause severe degradation to forecasts of the neutrino mass sum, Σ, approximately doubling σΣ. We show that including galaxy clustering constraints from Euclid and BOSS, and cosmic microwave background (CMB) Planck priors, can reduce this degradation to σΣ to 9 per cent and 16 per cent for the normal and inverted hierarchies, respectively. The combined forecasts, $\sigma _{\Sigma _{\rm {NH}}}=0.034\, \rm {eV}$ and $\sigma _{\Sigma _{\rm {IH}}}=0.034\, \rm {eV}$, preclude a meaningful distinction of the hierarchies but could be improved upon with future CMB priors on ns and information from neutrinoless double beta decay to achieve a 2σ distinction. The effect of intrinsic alignments on forecasts is shown to be minimal, with σΣ even experiencing mild improvements due to information from the intrinsic alignment signal. We find that while adiabatic contraction and intrinsic alignments will require careful calibration to prevent significant biasing of Σ, there is less risk presented by feedback from energetic events like AGN and supernovae.
Prospective Pilot Study of Cyclophosphamide as an Adjunct Treatment in Patients With Adult-Onset Immunodeficiency Associated With Anti-interferon-γ Autoantibodies
Authors: Laisuan Wannada , Pisitkun Prapaporn , Ngamjanyaporn Pintip , Suangtamai Thanitta , Rotjanapan Porpon
Published: January 2020

Background

Adult-onset immunodeficiency associated with interferon-γ autoantibody (IGA) is an emerging disease. The majority of patients require both antimicrobial and immunosuppressive treatments. However, anti-CD20 therapy is not fully accessible in a resource-limited setting to date.

Background

The objectives of this work were to study the efficacy of cyclophosphamide treatment and the role of laboratory biomarkers for disease progression monitoring.

Methods

A prospective pilot cohort study was conducted among patients with anti-interferon-γ autoantibodies (IGA) who had recurrent infections and required long-term antimicrobial therapy between 2015 and 2018. The patients were categorized into 2 groups: receipt of intravenous cyclophosphamide (IVCY) and receipt of anti-CD20 therapy (RTX). Clinical and laboratory data were determined.

Results

A total of 17 IGA patients were enrolled. Prolonged fever was the most common manifestation, and the most common infection identified was nontuberculous mycobacterial infections. Both were found in 88.24% of all patients.

After completion of IVCY, 9/11 patients achieved complete remission and tended to reach remission faster compared with individuals in the RTX group. The median duration from treatment initiation to remission (interquartile range) was 84 (42–154) days in the IVCY group and 99 (51–202) days in the RTX group. In remission patients, the biomarkers of interest had normalized after treatment, except interferon γ autoantibody titers. There were no differences in adverse events among the 2 groups.

Conclusion

IVCY may be considered as alternative therapy in this population, especially in resource-limited countries. A comparable clinical outcome to RTX may support its use on a larger scale. However, further study is encouraged.
Possible detection of solar gamma-rays by ground-level detectors in solar flares on 2011 March 7
Authors: Muraki Yasushi , Valdés-Galicia Jose F , González Luis Xavier , Kamiya Kohki , Katayose Yusaku , Koga Kiyokazu , Matsumoto Haruhisa , Masuda Satoshi , Matsubara Yutaka , Nagai Yuya , Ohnishi Munehiro , Ozawa Syunsuke , Sako Takashi , Shibata Shoichi , Takita Masato , Tanaka Yasuyuki , Tsuchiya Harufumi , Watanabe Kyoko , Zhang Ji Long
Published: January 2020

On 2011 March 7, the Solar Neutron Telescope located at Mt. Sierra Negra, Mexico (4600 m) observed enhancements of the counting rate from 19:57 to 20:04 UT with statistical significance 6.8σ and from 20:36 to 21:03 UT with 5.8σ. One plausible physical explanation for the observation enhancements is that they were produced by solar gamma-rays. The intensities were estimated to be (0.16 ± 0.03) photons cm−2 s−1 for the first flare and (0.22 ± 0.04) photons cm−2 s−1 for the second one at the top of the atmosphere. As far as we know, this is the first report on the detection of solar gamma-rays with a ground-based detector. In association with these events, the solar neutron detector Space Environment Data Acquisition Equipment on board the International Space Station registered two solar neutrons with statistical significances of 7.3σ and 6.6σ. The Large Area Telescope on board the Fermi observatory also observed high-energy gamma-rays from this flare with a statistical significance of 6.7σ. In this paper we propose a unified model to explain the production mechanism of high-energy gamma-rays and neutrons in association with this flare.
Mapping Housing Laws in the United States: A Resource for Evaluating Housing Policies' Impacts on Health
Authors: Moran-McCabe Katie , Waimberg Joshua , Ghorashi Adrienne
Published: January 2020

Context:

Safe, stable housing is essential to good health. Housing hazards, including mold, vermin, and lead, can contribute to the development or exacerbation of chronic illnesses such as asthma and neurological disorders. In addition, eviction has been associated with poor physical and mental health outcomes. There are many laws aimed at maintaining healthy housing, or protecting access to stable housing, but their impacts are mostly unknown.

Policy:

Using scientific legal mapping, the Center for Public Health Law Research (the Center) created legal data sets on state landlord-tenant laws, state fair housing laws, and city nuisance property ordinances. These data sets track the incidence and key features of these laws, creating legal data that can be used for evaluation. Some important elements of these laws include property maintenance duties; protections against retaliation; protected classes under state fair housing laws; discriminatory acts prohibited by state fair housing laws; types of conduct that constitute nuisance activity; and required nuisance abatement actions.

Implementation and/or Dissemination:

As of August 1, 2017, all 50 states and the District of Columbia have a state landlord-tenant law; all states except Mississippi have a state fair housing law; and 37 of the 40 most populous US cities have a local nuisance property ordinance.

Evaluation:

Evaluation of these laws is needed to determine their effectiveness and impacts and to spread the use of evidence-based policies. The creation of these legal data sets is the first step toward evaluation.

Discussion:

Law can play an important role in promoting healthy housing, but evaluating the law is essential to determining its impact. Tracking the prevalence and key elements of laws is an important first step in conducting evaluation. The legal data created by the Center can be used to evaluate the efficacy and impacts of state landlord-tenant laws, state fair housing protections, and city nuisance property ordinances.
Short-term consumption of a high-fat diet increases host susceptibility to Listeria monocytogenes infection
Authors: Heras Vanessa , Clooney Adam G. , Ryan Feargal J. , Cabrera-Rubio Raul , Casey Pat G. , Hueston Cara M. , Pinheiro Jorge , Rudkin Justine K. , Melgar Silvia , Cotter Paul , Hill Colin , Gahan Cormac
Published: January 2020

A Westernized-diet comprising a high caloric intake from animal fats is known to influence the development of pathological inflammatory conditions. However, there has been relatively little focus upon the implications of such diets for the progression of infectious disease. Here we investigated the influence of a high-fat (HF) diet upon parameters that influence Listeria monocytogenes infection in mice.

We determined that short-term administration of a HF diet increases the number of goblet cells, a known binding site for the pathogen in the gut, and also induces profound changes to the microbiota and promotes a pro-inflammatory gene expression profile in the host. Host physiological changes were concordant with significantly increased susceptibility to oral L. monocytogenes infection in mice fed a HF diet relative to low-fat (LF) or chow-fed animals. Prior to Listeria infection short-term consumption of HF diet elevated faecal levels of Firmicutes. During active infection with L. monocytogenes microbiota changes were further exacerbated but host inflammatory responses were significantly down-regulated relative to Listeria-infected LF or chow-fed groups, suggestive of a profound tampering of the host response influenced by infection in the context of a HF diet.

Overall the results indicate that short-term consumption of a Westernized-diet has the capacity to significantly alter host susceptibility to L. monocytogenes infection concomitant with changes to the host physiological landscape. The findings suggest that diet should be a consideration when developing models that reflect human infectious disease.
Defining the link between efflux pumps and biofilm formation
Authors: Holden Emma , Webber Mark
Published: January 2020

Biofilms are intrinsically important to our understanding of bacterial pathogens. The majority of bacterial life exists as part of a biofilm, as despite this, we have very little understanding of the genetic pathways that facilitate and drive biofilm formation. Work in our group has outlined a phenotypic link between efflux pump activity and biofilm formation, both of which have been implicated in decreased susceptibility to multiple antibiotics. Genetic or chemical inactivation of efflux results in a substantial decrease in biofilm formation. We have determined that this is due to transcriptional repression of one of the main components of the biofilm: the amyloid fibrous protein, curli. This relationship between efflux activity and biofilm formation has been identified in many Gram-negative and Gram-positive bacterial pathogens, but the regulatory network through which these phenotypes are linked is unknown. My PhD project aims to determine the pathway that links efflux pump activity and biofilm formation. I will investigate this using TraDIS, which is a large-scale transposon mutagenesis approach that will be used to determine all of the genes responsible for efflux activity and biofilm formation. My poster will present preliminary results from this genome-wide screen in E. coli. I will outline the further work to be undertaken, including repeating this experiment in Salmonella Typhimurium and formulating and testing hypotheses as to how efflux activity and biofilm formation are linked in both species. This will overall improve our understanding of important mechanisms of antimicrobial resistance in human pathogens.
Carbapenem-resistant Enterobacteriaceae : A serious concern in cancer patients
Authors: Biswas Sanjay , Bhat Vivek , Kelkar Rohini
Published: January 2020

Introduction. Gram-negative bacteria, including Enterobacteriaceae, are an important cause of infections in cancer patients. Members of Enterobacteriaceae are commonly isolated from bloodstream infections, surgical site infections, urinary tract infections, and lower respiratory tract infections. There has been an increase in the isolation of gram-negative MDRO’s over the years with ESBL’s and for the last few years with carbapenem-resistant Enterobacteriaceae (CRE). CRE’s have become a serious threat to cancer patients.

Material & Methods. A total of 61331 clinical samples from 19015 patients were received in the Dept of Microbiology, Tata Memorial Center, Mumbai, India during January 2018 to May 2019. All the samples were processed as per routine microbiological procedures and antimicrobial susceptibility testing was performed as per CLSI guidelines.

Results. Blood was the commonest sample received followed by urine, respiratory tract samples, surgical site samples and sterile body fluids. E. coli was the commonest microorganism isolated followed by Klebsiella pneumoniae, P. aeruginosa, S. aureus, Acinetobacter sp., Enterobacter sp. and Enterococci. Colistin was the most susceptible antibiotic for gram negative organisms followed by tigecycline, aminoglycosides, cefoperazone-sulbactam and piperacillin-tazobactam. Overall 77.8% CRE’s were detected whereas it was 81.8% in LRTI, followed by 82.5% in UTI, 79.1% in BSI and 75% in SSI.

Conclusion. The increasing prevalence of CRE infections represents a major threat to cancer patients. With the high mortality of CRE infections and increasing resistance to available antibiotics, it is urgent for the medical community to develop new and effective therapeutic strategies. Robust anti-microbial stewardship is the need of the hour.
Whole genome sequencing reveals genetic diversity in Mycobacterium avium subspecies paratuberculosis population circulating in Irish cattle
Authors: Perets Viktor , Cassidy Sophie , Kenny Kevin , O'Connor Aoife , O'Mahony Jim , Crispell Joseph , Gordon Stephen
Published: January 2020

Mycobacterium avium subspecies paratuberculosis (MAP) causes Johne’s Disease (JD), a chronic enteritis, in cattle. Whole genome sequencing (WGS) has been applied to many pathogen systems, where its unprecedented resolution has greatly enhanced our understanding of the molecular epidemiology of pathogen transmission. However, WGS has seen limited application to MAP; understanding the transmission dynamics of MAP will inform control of JD. We report the first study into the application of WGS to MAP in Ireland.

DNA was extracted from 167 MAP isolates sourced from cattle across Ireland. Libraries were prepared and sequenced on an Illumina-NextSeq500 platform. Sequencing data were processed using an in-house bioinformatic pipeline, which trimmed reads, aligned them to the reference genome MAP K10, followed by variant calling, quality filtering and construction of a maximum-likelihood phylogeny. DNA extracts were also used for MIRU-VNTR typing.

The resulting phylogeny shows that the MAP population present in Irish cattle is genetically diverse, which may have resulted from importation of MAP strains from across Europe into Ireland. Similar diversity was observed in a WGS study that noted the impact of cattle imports on the Canadian MAP population. Some Irish isolates were genetically similar to European and Canadian isolates.

Comparing our WGS data with MIRU-VNTR indicates that MIRU-VNTR has limited resolution for discriminating MAP strains, and often does not distinguish isolates to sufficient resolution.

The genomic data presented here provide the first snapshot of genetic diversity of Irish MAP and a baseline for future studies into spread and persistence of MAP in Irish cattle.
Using metagenomics to investigate the impact of hospital stay and the ARK intervention on the human gut resistome
Authors: Yokoyama Maho , Peto Leon , Walker A. Sarah , Llewelyn Martin
Published: January 2020

Antimicrobials are vital for modern medicine. Antimicrobial use selects for antimicrobial resistant bacteria, particularly among the gut microflora. Minimising antimicrobial resistance (AMR) selection by avoiding unnecessary antibiotic use helps combat AMR. Metagenomic analyses have the potential to provide accurate detection and quantification of AMR genes within an individual’s gut microbiome (gut ‘resistome’), allowing the impact of different types of antibiotic exposures to be evaluated and guide interventions to reduce AMR.

We have developed a short-read sequencing approach to characterise the gut ‘resistome’ and piloted this in two clinical sample sets.

The first consisted of paired stool samples from older hospitalised adults. 25 pairs of samples (1 to 50 days apart) showed a median AMR gene reads/kb/million total reads (RPKM) of 1841 (124 to 17,832), and a median AMR gene count of 55 (2 to 101).

The second consisted of faecal discards from Clostridium difficile testing at a hospital eleven months apart. In these samples (n=21) the median AMR gene read was 923 RPKM (240 to 19,475), and the median AMR gene count was 36 (9 to 82).

In both sample sets there was a trend towards an increase in AMR gene RPKM and number between the time points. dfrF, ErmB and tetW were the commonest AMR genes in both sample sets.

This approach is being applied to analyse the impact of an intervention (ARK-Hospital) designed to change antibiotic prescribing behaviour. The data will allow us to determine the patient-level impact of reduced antibiotic exposure on carried AMR.
The role of the cingulate cortex in the generation of motor tics and the experience of the premonitory urge-to-tic in Tourette syndrome
Authors: Jackson Stephen R. , Sigurdsson Hilmar P. , Dyke Katherine , Condon Maria , Jackson Georgina M.
Published: January 2020

Tourette syndrome (TS) is a neurological disorder of childhood onset that is characterised by the occurrence of motor and vocal tics. TS is associated with cortical-striatal-thalamic-cortical circuit [CSTC] dysfunction and hyper-excitability of cortical limbic and motor regions that are thought to lead to the occurrence of tics. Individuals with TS often report that their tics are preceded by ‘premonitory sensory/urge phenomena’ (PU) that are described as uncomfortable bodily sensations that precede the execution of a tic and are experienced as a strong urge for motor discharge. While the precise role played by PU in the occurrence of tics is largely unknown, they are nonetheless of considerable theoretical and clinical importance as they form a core component of many behavioural therapies used in the treatment of tic disorders. Recent evidence indicates that the cingulate cortex may play an important role in the generation of PU in TS, and in ‘urges-for-action’ more generally. In the current study we utilised voxel-based morphometry (VBM) techniques, together with ‘seed-to-voxel’ structural covariance network (SCN) mapping, to investigate the putative role played by the cingulate cortex in the generation of motor tics and the experience of PU in a relatively large group of young people with TS. Whole-brain VBM analysis revealed that TS was associated with clusters of significantly reduced grey matter volumes bilaterally within: the orbito-frontal cortex; the cerebellum; and the anterior and mid cingulate cortex. Similarly, analysis of SCNs associated with bilateral mid- and anterior-cingulate ‘seed’ regions demonstrated that TS is associated withincreasedstructural covariance primarily with the bilateral motor cerebellum; the inferior frontal cortex; and the posterior cingulate cortex.
The dynamics of the improvising brain: a study of musical creativity using jazz improvisation
Authors: Da Mota Patricia Alves , Fernandes Henrique M , Stark Eloise , Cabral Joana , Heggli Ole Adrian , Sousa Nuno , Kringelbach Morten L , Vuust Peter
Published: January 2020

The neuroscience of jazz improvisation has shown promising results for understanding domain-specific and domain-general processes of creativity. Here, we used fMRI to measure for the first time the dynamic neural substrates of musical creativity in 16 skilled jazz pianists while they played by memory, improvised freely (iFreely) and by melody (iMelody), and during resting-state. We used the Leading Eigenvector Dynamics Analysis (LEiDA) to examine how different modes of improvisation (musical creativity) evolve over time, and which cognitive mechanisms are responsible for different stages of musical creation. Our results reveal that a substate comprising auditory, sensorimotor and posterior salience networks had a significantly higher probability of occurrence (POc) in both modes of improvisation than in resting-state and play by memory. Another substate comprising the default mode (DMN), executive control (ECN) and language networks had significantly lower POc iniFreelythan in resting-state, withiMelodyhaving a higher POc thaniFreely.Such indicates thatiMelody,a more constrained form of creativity involves a higher recurrence of subsystems responsible for goal-directed cognition and cognitive control processes. On the other hand,iFreelyrecruits brain networks responsible for generation of spontaneous musical creativity. Overall, this study brings new insights into the large-scale brain mechanisms supporting and promoting the complex process of creativity, specifically in the context of jazz improvisation, as well as the relevance of different improvisation modes in creativity research.
Low contribution of rare species to resilience and adaptive capacity in novel spatial regimes arising from biome shifts caused by global change
Authors: Angeler David G. , Roberts Caleb P. , Twidwell Dirac , Allen Craig R.
Published: January 2020

Human activity causes biome shifts that alter biodiversity and spatial resilience patterns, ultimately challenging conservation. Rare species, often considered vulnerable to change and endangered, can be a critical element of resilience by providing adaptive capacity in response to disturbances. However, little is known about changes in rarity and dominance patterns of communities once a biome transitions into a novel spatial regime, and how this affects conservation. We used time series modeling to identify species rarity and dominance patterns in an expanding terrestrial (southern) spatial regime in the North American Great Plains and another (northern) regime that will become encroached by the southern regime in the near future. In this approach, presumably rare and abundant species show stochastic and deterministic dynamics, respectively. We specifically assessed how stochastic species of the northern spatial regime influence the resilience and adaptive capacity of a novel spatial regime once it has been encroached by the southern regime by either becoming deterministic or staying stochastic. Using 47 years (1968 – 2014) of breeding bird survey data and a space-for-time substitution, we found half of the stochastic species from the northern regime to be either deterministic or stochastic in the southern regime. However, the overall contribution of these species to the community of the southern regime was low, manifested in marginal contributions to resilience and adaptive capacity of this regime. Also, none of these species were of conservation concern, suggesting limited need for revised species conservation action in the novel spatial regime. From a systemic perspective our result suggest that while stochastic species can potentially compensate for the loss of dominant species after disturbances and maintain the system in its current regime, they may only marginally contribute to resilience and adaptive capacity in a new spatial regime after fundamental ecological changes have occurred.
Observed but Never Experienced – Vicarious Learning of Fear Under Ecological Conditions
Authors: Szczepanik Michał , Kaźmierowska Anna M. , Michałowski Jarosław M. , Wypych Marek , Olsson Andreas , Knapska Ewelina
Published: January 2020

Learning to avoid threats often occurs by observing the behavior of others. Most previous research on observational fear learning in humans has used pre-recorded stimuli as social cues. Here, we aimed to enhance the ecological validity of the learning situation: the ‘observer’ watched their friend (‘demonstrator’) performing a differential fear-conditioning task in real time. During the task, one conditioned stimulus (CS+) was repeatedly linked with electric stimulation (US) while another one (CS-) was always safe. Subsequently, the observer was presented with the CS+ and CS- directly but without receiving any shocks. Skin conductance (SCR) and fear-potentiated startle (FPS) responses were measured in observers throughout the whole experiment. While the US applied to the demonstrator elicited strong SCR in the observers, subsequent differential SCR to CSs (CS+ vs. CS-) presented directly were dependent on declarative knowledge of the CS+/US contingency. Contingency-aware observers also showed elevated FPS during both CS+ and CS- compared to intertrial intervals. We conclude that observational fear learning involves two components: an automatic emotional reaction to the response of the demonstrator and learning to predict stimulus contingency (CS+/US pairing). Ecological modifications proposed offer new perspectives on studying social learning of emotions.
Interrogating surface versus intracellular transmembrane receptor populations using cell-impermeable SNAP-tag substrates
Authors: Poc Pascal , Gutzeit Vanessa A. , Ast Julia , Lee Joon , Jones Ben J. , D’Este Elisa , Mathes Bettina , Hodson David J. , Levitz Joshua , Broichhagen Johannes
Published: January 2020

Employing self-labelling protein tags for the attachment of fluorescent dyes has become a routine and powerful technique in optical microscopy to visualize and track fused proteins. However, membrane permeability of the dyes and the associated background signals can interfere with the analysis of extracellular labeling sites. Here we describe a novel approach to improve extracellular labeling by functionalizing the SNAP-tag substrate benzyl guanine (“BG”) with a charged sulfonate (“SBG”). This chemical manipulation improves solubility, reduces non-specific staining and renders the bioconjugation handle impermeable while leaving its cargo untouched. We report SBG-conjugated fluorophores across the visible spectrum, which cleanly label SNAP-fused proteins in the plasma membrane of living cells. We demonstrate the utility of SBG-conjugated fluorophores to interrogate class A, B and C G protein-coupled receptors (GPCRs) using a range of imaging approaches including nanoscopic super-resolution imaging, analysis of GPCR trafficking from intra- and extracellular pools,in vivolabelling in mouse brain and analysis of receptor stoichiometry using single molecule pull down.
A novel fibrinogen gamma-chain mutation, p. γAla327Val, causes structural abnormality of D region and ultimately leads to congenital dysfibrinogenemia
Authors: Wei Aiqiu , Wu Yangyang , Xiang Liqun , Yan Jie , Cheng Peng , Deng Donghong , Lin Faquan
Published: January 2020

Congenital dysfibrinogenemia (CD) is a coagulation disorder caused by mutations in the fibrinogen gene, which result in abnormal fibrinogen function. Many studies have confirmed that over half of dysfibrinogenemia cases are asymptomatic. In this study, we aimed to investigate the pathogenesis of CD caused by γ Ala327Val heterozygous mutation, a new mutation, by studying fibrinogen function. Blood samples of patients were collected and the coagulation function, fibrinogen (Fg) aggregation test, fibrin clot lysis test, and SDS-PAGE were performed. Coagulation was monitored using a thromboelastometer, and the fibrin clot network structure was observed by scanning electron microscopy. The effect of the mutation on fibrinogen structure and function was predicted by molecular modeling. The fibrinogen activity concentration in patients with CD was significantly lower than that in healthy individuals. Thromboelastography showed that the K value of patients with CD was higher than that for healthy individuals. The Angle values were also decreased. The function of fibrinogen in patients with CD was low. Compared to fibrinogen from healthy individuals, fibrin size was different, the fiber network structure was loose, the pore size was increased, and the fiber branch nodes were increased for fibrinogen isolated from the proband. The γ Ala327Val mutation led to changes in the structure of fibrinogen D region, affecting its structural stability. Ala327Val heterozygous missense mutation in exon 8 of FGG gene γ-chain thus leads to abnormal fibrinogen structure and impairs the aggregation function of fibrinogen. This mutation is reported here for the first time.
The Maryland Analysis of Developmental EEG (MADE) Pipeline
Authors: Debnath Ranjan , Buzzell George A. , Morales Santiago , Bowers Maureen E. , Leach Stephanie C. , Fox Nathan A.
Published: January 2020

Compared to adult EEG, EEG signals recorded from pediatric populations have shorter recording periods and contain more artifact contamination. Therefore, pediatric EEG data necessitate specific preprocessing approaches in order to remove environmental noise and physiological artifacts without losing large amounts of data. However, there is presently a scarcity of standard automated preprocessing pipelines suitable for pediatric EEG.

In an effort to achieve greater standardization of EEG preprocessing, and in particular for the analysis of pediatric data, we developed the Maryland Analysis of Developmental EEG (MADE) pipeline as an automated preprocessing pipeline compatible with EEG data recorded with different hardware systems, different populations, levels of artifact contamination, and length of recordings. MADE uses EEGLAB and functions from some EEGLAB plugins, and includes additional customizable features particularly useful for EEG data collected from pediatric populations.

MADE processes event-related and resting state EEG from raw data files through a series of preprocessing steps and outputs processed clean data ready to be analyzed in time, frequency, or time-frequency domain. MADE provides a report file at the end of the preprocessing that describes a variety of features of the processed data to facilitate the assessment of the quality of processed data. In this paper we discuss some practical issues, which are specifically relevant to pediatric EEG preprocessing. We also provide custom-written scripts to address these practical issues.

MADE is freely available under the terms of the GNU General Public License athttps://github.com/ChildDevLab/MADE-EEG-preprocessing-pipeline.
A Reporter Mouse forIn VivoDetection of DNA Damage in Embryonic Germ Cells
Authors: Bloom Jordana C. , Schimenti John C.
Published: January 2020

Maintaining genome integrity in the germline is essential for survival and propagation of a species. In both mouse and human, germ cells originate during fetal development and are hypersensitive to both endogenous and exogenous DNA damaging agents. Currently, mechanistic understanding of how primordial germ cells respond to DNA damage is limited in part by the tools available to study these cells. We developed a mouse transgenic reporter strain expressing a 53BP1-mCherry fusion protein under the control of the Oct4ΔPE embryonic germ cell-specific promoter. This reporter binds sites of DNA double strand breaks (DSBs) on chromatin, forming foci. Using ionizing radiation as a DNA double strand break-inducing agent, we show that the transgenic reporter expresses specifically in the embryonic germ cells of both sexes and forms DNA damage induced foci in both a dose- and time-dependent manner. The dynamic time-sensitive and dose-sensitive DNA damage detection ability of this transgenic reporter, in combination with its specific expression in embryonic germ cells, makes it a versatile and valuable tool for increasing our understanding of DNA damage responses in these unique cells.
The proteasomal deubiquitinating enzyme PSMD14 regulates macroautophagy by controlling Golgi-to-ER retrograde transport
Authors: Bustamante HA , Cereceda K , González AE , Valenzuela GE , Cheuquemilla Y , Hernández S , Arias-Muñoz E , Cerda-Troncoso C , Bandau S , Soza A , Kausel G , Kerr B , Mardones GA , Cancino J , Hay RT , Rojas-Fernandez A , Burgos PV
Published: January 2020

Ubiquitination regulates several biological processes. Here, we search for ubiquitin-related genes implicated in protein membrane trafficking performing a High-Content siRNA Screening including 1,187 genes of the human “ubiquitinome” using Amyloid Precursor Protein (APP) as a reporter. We identified the deubiquitinating enzyme PSMD14, a subunit of the 19S regulatory particle of the proteasome, specific for K63-Ub chains in cells, as a novel key regulator of Golgi-to-endoplasmic reticulum (ER) retrograde transport. Silencing or pharmacological inhibition of PSMD14 caused a robust and rapid inhibition of Golgi-to-ER retrograde transport which leads to a potent blockage of macroautophagy by a mechanism associated with the retention of Atg9A and Rab1A at the Golgi apparatus. Because pharmacological inhibition of the proteolytic core of the 20S proteasome did not recapitulate these effects, we concluded that PSMD14, and their K-63-Ub chains, act as a crucial regulator factor for macroautophagy by controlling Golgi-to-ER retrograde transport.
Near-atomic structures of the BBSome reveal a novel mechanism for transition zone crossing
Authors: Bahl Kriti , Yang Shuang , Chou Hui-Ting , Woodsmith Jonathan , Stelzl Ulrich , Walz Thomas , Nachury Maxence V.
Published: January 2020

The BBSome is a complex of eight Bardet-Biedl Syndrome (BBS) proteins that removes signaling receptors from cilia. The GTPase ARL6/BBS3 recruits the BBSome to the ciliary membrane where the BBSome–ARL6GTPcomplex ferries G protein-coupled receptors (GPCRs) across the transition zone, a diffusion barrier at the base of cilia. Here, we find that the BBSome undergoes a conformational change upon recruitment to membranes by ARL6GTP. Modeling the binding of the BBSome to membranes and to the GPCR Smoothened (SMO) reveals that the amphipathic helix 8 of SMO must be released from the membrane for SMO to be recognized by the BBSome. Underscoring the functional importance of amphipathic helix extraction in TZ crossing, we find that exchanging the amphipathic helix of ARL6 for one that embeds deeper into the membrane blocks BBSome-mediated exit of GPCRs from cilia. We propose that the rigid curvature and dense lipid packing of the transition zone reject asymmetric insertions in the inner leaflet and that the BBSome licenses transition zone crossing by extracting bulky amphipathic helices from the inner leaflet.
Transposase assisted tagmentation of RNA/DNA hybrid duplexes
Authors: Lu Bo , Dong Liting , Yi Danyang , Zhu Chenxu , Zhang Meiling , Li Xiaoyu , Yi Chengqi
Published: January 2020

Tn5-mediated transposition of double-strand DNA has been widely utilized in various high-throughput sequencing applications. Here, we report that the Tn5 transposase is also capable of direct tagmentation of RNA/DNA hybridsin vitro. As a proof-of-concept application, we utilized this activity to replace the traditional library construction procedure of RNA sequencing, which contains many laborious and time-consuming processes. Results of activity of transposase assisted RNA/DNA hybrids co-tagmentation (termed “ATRAC-seq”) are comparable to traditional RNA-seq methods in terms of gene number, gene body coverage and gene expression analysis; at the meantime, ATRAC-seq enables a one-tube library construction protocol and hence is more rapid (within 8 h) and convenient. We expect this tagmentation activity on RNA/DNA hybrids to have broad potentials on RNA biology and chromatin research.
Using EEG to understand how our brain elaborate information in stated choice experiments: Easy versus hard tasks in the choice of vehicles
Authors: Cherchi Elisabetta , Vuong Quoc C , Stergiou Antonia
Published: January 2020

In the current study, we aim to provide preliminary evidence that complex consumer choices depends on cognitive processes and executive functions that may not be fully captured by current stated choice (SC) approaches. To address this gap, here we combine the standard SC experiment with electroencephalogram (EEG) recordings while manipulating the cognitive demands of the task. Our study is applied to the choice context of a car purchase between a petrol and an electric vehicle. Respondents were asked to fill in a stated choice experiment online and a subsample of these respondents were then invited to participate in an EEG study during which they repeated the same SC experiment while we continuously recorded EEG signals from their scalp. We then modelled people’s choice behaviours in easy and hard decisions, and compared this analysis of their choice behaviour to their EEG responses in these two conditions. Our results confirm that hard decisions lead to higher cognitive demands and larger EEG responses in electrodes on the frontal part of the scalp and these demands can lead to choices inconsistent with the compensatory assumptions.
Mapping the nucleolar proteome reveals a spatiotemporal organization related to intrinsic protein disorder
Authors: Stenström Lovisa , Mahdessian Diana , Gnann Christian , Cesnik Anthony J. , Ouyang Wei , Leonetti Manuel D. , Uhlén Mathias , Cuylen-Häring Sara , Thul Peter J. , Lundberg Emma
Published: January 2020

The nucleolus is essential for ribosome biogenesis and is involved in many other cellular functions. We performed a systematic spatiotemporal dissection of the human nucleolar proteome using confocal microscopy. In total, 1,318 nucleolar proteins were identified; 287 were localized to fibrillar components, and 157 were enriched along the nucleoplasmic border, indicating a potential fourth nucleolar subcompartment (nucleoli rim). We found 65 nucleolar proteins (36 uncharacterized) to relocate to the chromosomal periphery during mitosis. Interestingly, we observed temporal partitioning into two recruitment phenotypes: early (prometaphase) and late (after metaphase), suggesting phase-specific functions. We further show that expression of MKI67 is critical for this temporal partitioning. We provide the first proteome-wide analysis of intrinsic protein disorder for the human nucleolus and show that nucleolar proteins in general, and mitotic chromosome proteins in particular, have significantly higher intrinsic disorder level compared to cytosolic proteins. In summary, this study provides a comprehensive and essential resource of spatiotemporal expression data for the nucleolar proteome as part of the Human Protein Atlas.
Endothelial TGF-β signaling instructs smooth muscle development in the cardiac outflow tract
Authors: Boezio Giulia L.M. , Bensimon-Brito Anabela , Piesker Janett , Guenther Stefan , Helker Christian S.M. , Stainier Didier Y.R.
Published: January 2020

The development of the cardiac outflow tract (OFT), which connects the heart to the great arteries, relies on a complex crosstalk between endothelial (ECs) and smooth muscle (SMCs) cells. Defects in OFT development can lead to severe malformations, including aortic aneurysms, which have often been associated with impaired TGF-β signaling. To further investigate the role of TGF-β signaling in OFT formation, we generated zebrafish lacking the type I TGF-β receptor Alk5 and found a strikingly specific dilation of the OFT.alk5mutants also exhibit increased EC numbers, extracellular matrix (ECM) and SMC disorganization. Surprisingly, endothelial-specificalk5overexpression inalk5mutants rescues both endothelial and SMC defects. Furthermore, modulation of the ECM genefibulin-5, a TGF-β target, partially restores OFT morphology and function. These findings reveal a new requirement for endothelial TGF-β signaling in OFT morphogenesis and suggest an important role for the endothelium in the etiology of aortic malformations.
N6-methyladenosine in poly(A) tails stabilizeVSGtranscripts
Authors: Viegas Idalio J. , de Macedo Juan Pereira , De Niz Mariana , Rodrigues João A. , Aresta-Branco Francisco , Jaffrey Samie R. , Figueiredo Luisa M.
Published: January 2020

RNA modifications are important regulators of gene expression. InTrypanosoma brucei, transcription is polycistronic and thus most regulation happens post-transcriptionally.N6-methyladenosine (m6A) has been detected in this parasite, but its function remains unknown. Here we show that ∼50% of the m6A is located in the poly(A) tail of the monoallelically expressed Variant Surface Glycoprotein (VSG) transcript. m6A residues are removed from theVSGpoly(A) tail prior to deadenylation and mRNA degradation. Using genetic tools, we identified a 16-mer motif in the 3’UTR ofVSGthat acts as a cis-acting motif required for inclusion of m6A in the poly(A) tail. Removal of this motif from theVSG3’ UTR results in poly(A) tails lacking m6A, rapid deadenylation and mRNA degradation. To our knowledge this is the first identification of an RNA modification in the poly(A) tail of any eukaryote, uncovering a novel post-transcriptional mechanism of gene regulation.