bluuebunny/crossref_metadata_2025 huggingface dataset:
The dependence of AGN activity on environment in SDSS
Authors: Man Zhong-yi , Peng Ying-jie , Kong Xu , Guo Ke-xin , Zhang Cheng-peng , Dou Jing
Published: June 2019

Environment is one of the key external drivers of the galaxies, while active galactic nucleus (AGN) is one of the key internal drivers. Both of them play fundamental roles in regulating the formation and evolution of galaxies. We explore the interrelationship between environment and AGN in SDSS. At a given stellar mass, the specific star formation rate distribution of the AGN host galaxies remains unchanged with overdensity, with the peak of the distribution around the Green Valley. We show that, at a given stellar mass, the AGN fraction that has been commonly used in previous studies (defined as the number of AGNs relative to all galaxies including passive and star forming ones) does decrease with increasing overdensity for satellites. This is largely due to the fact that the fraction of passive galaxies strongly depends on environment. In order to investigate the intrinsic correlation between AGN and environment, especially under the assumption that AGN feedback is responsible for star formation quenching, the AGN fraction should be defined as the number of AGNs relative to the star-forming galaxies only. With the new definition, we find little dependence of AGN fraction on overdensity, central/satellite, and group halo mass. There is only marginal evidence that AGN may prefer denser regions, which is possibly due to more frequent interaction of galaxies or higher merger rate in groups. Our results support the scenario that internal secular evolution is the predominant mechanism of triggering AGN activity, while external environment related processes only play a minor role.
The diversity of the circumgalactic medium around z = 0 Milky Way-mass galaxies from the Auriga simulations
Authors: Hani Maan H , Ellison Sara L , Sparre Martin , Grand Robert J J , Pakmor Rüediger , Gomez Facundo A , Springel Volker
Published: June 2019

Galaxies are surrounded by massive gas reservoirs (i.e. the circumgalactic medium; CGM) which play a key role in their evolution. The properties of the CGM, which are dependent on a variety of internal and environmental factors, are often inferred from absorption line surveys which rely on a limited number of single lines-of-sight. In this work we present an analysis of 28 galaxy haloes selected from the Auriga project, a cosmological magneto-hydrodynamical zoom-in simulation suite of isolated Milky Way-mass galaxies, to understand the impact of CGM diversity on observational studies. Although the Auriga haloes are selected to populate a narrow range in halo mass, our work demonstrates that the CGM of L⋆ galaxies is extremely diverse: column densities of commonly observed species span ∼3 − 4 dex and their covering fractions range from ${\sim } 5$ to $90{{\ \rm per\ cent}}$. Despite this diversity, we identify the following correlations: 1) the covering fractions (CF) of hydrogen and metals of the Auriga haloes positively correlate with stellar mass, 2) the CF of H i, C iv, and Si ii anticorrelate with active galactic nucleus luminosity due to ionization effects, and 3) the CF of H i, C iv, and Si ii positively correlate with galaxy disc fraction due to outflows populating the CGM with cool and dense gas. The Auriga sample demonstrates striking diversity within the CGM of L⋆ galaxies, which poses a challenge for observations reconstructing CGM characteristics from limited samples, and also indicates that long-term merger assembly history and recent star formation are not the dominant sculptors of the CGM.
Do reverberation mapping analyses provide an accurate picture of the broad-line region?
Authors: Mangham S W , Knigge C , Williams P , Horne Keith , Pancoast A , Matthews J H , Long K S , Sim S A , Higginbottom N
Published: June 2019

Reverberation mapping (RM) is a powerful approach for determining the nature of the broad-line region (BLR) in active galactic nuclei. However, inferring physical BLR properties from an observed spectroscopic time series is a difficult inverse problem. Here, we present a blind test of two widely used RM methods: MEMEcho (developed by Horne) and CARAMEL (developed by Pancoast and collaborators). The test data are simulated spectroscopic time series that track the Hα emission line response to an empirical continuum light curve. The underlying BLR model is a rotating, biconical accretion disc wind, and the synthetic spectra are generated via self-consistent ionization and radiative transfer simulations. We generate two mock data sets, representing Seyfert galaxies and QSOs. The Seyfert model produces a largely negative response, which neither method can recover. However, both fail ‘gracefully', neither generating spurious results. For the QSO model both CARAMEL and expert interpretation of MEMEchoś output both capture the broadly annular, rotation-dominated nature of the line-forming region, though MEMEcho analysis overestimates its size by 50 per cent, but CARAMEL is unable to distinguish between additional inflow and outflow components. Despite fitting individual spectra well, the CARAMEL velocity-delay maps and RMS line profiles are strongly inconsistent with the input data. Finally, since the Hα line-forming region is rotation dominated, neither method recovers the disc wind nature of the underlying BLR model. Thus considerable care is required when interpreting the results of RM analyses in terms of physical models.
Population synthesis of accreting neutron stars emitting gravitational waves
Authors: Gittins Fabian , Andersson Nils
Published: June 2019

The fastest-spinning neutron stars in low-mass X-ray binaries, despite having undergone millions of years of accretion, have been observed to spin well below the Keplerian break-up frequency. We simulate the spin evolution of synthetic populations of accreting neutron stars in order to assess whether gravitational waves can explain this behaviour and provide the distribution of spins that is observed. We model both persistent and transient accretion and consider two gravitational-wave-production mechanisms that could be present in these systems: thermal mountains and unstable rmodes. We consider the case of no gravitational-wave emission and observe that this does not match well with observation. We find evidence for gravitational waves being able to provide the observed spin distribution; the most promising mechanisms being a permanent quadrupole, thermal mountains, and unstable r modes. However, based on the resultant distributions alone, it is difficult to distinguish between the competing mechanisms.
Diverging identities: a model of class formation
Authors: Collier Paul
Published: June 2019

This paper is an application of Identity Economics. Since the literature in this field is recent, the paper begins with an extensive review of the key contributions. The current paper analyses the process and psychological costs of social polarization arising from economic inequalities. It may have some application to the current social divisions evident in the votes for Brexit and Donald Trump, and protest movements such as the gilets jaunes. In a simple model, people rationally maximize their utility from esteem, by selecting a subjective salient identity from two objective identities: nationality and job. The model shows how an increase in wages for the upper half of the population can lead those with high incomes to drop nationality as their salient identity, forming a new ‘elite’ class. This rational switch in the identity of high-income workers has efficiency and redistributive effects, reducing aggregate utility and generating regressive transfers.
Direct Repair of Iatrogenic Vertebral Artery Injury Associated With Anterior Cervical Corpectomy: 2-Dimensional Operative Video
Authors: Almefty Rami O , Albuquerque Felipe C , Spetzler Robert F , Turner Jay D
Published: June 2019

Vertebral artery (VA) injury during anterior cervical spine surgery has potentially devastating neurovascular consequences. Our video highlights the operative nuances of exposing and directly repairing the V2 segment of the VA from an anterior approach. A 67-year-old woman undergoing anterior cervical corpectomy at another hospital began briskly bleeding from a suspected VA injury. Upon emergency transfer of the patient to our facility, angiography confirmed a right VA pseudoaneurysm at the level of the C5 corpectomy. The decision was made to repair the VA directly, thus avoiding vessel sacrifice and stenting. The previous anterior exposure was reopened. The longus colli was mobilized laterally on the right side to expose the C4 and C6 anterior tubercles. A plane was developed in the transverse foramina from C4 to C6, and the foramina were unroofed anteriorly using a high-speed drill and Kerrison rongeurs. The injured segment of the VA was exposed, and the platelet plug over the injured VA was identified. The proximal and distal ends of the injured segment were temporarily clipped, and the platelet plug was removed, revealing a small, ovoid-shaped' full-thickness arterial wall defect. The VA injury was repaired with simple running 10-0 nylon sutures. Indocyanine green angiography confirmed rapid filling of the patent lumen. The corpectomy and anterior fixation were completed. The patient was placed on aspirin therapy postoperatively. The patient remained neurologically intact without neurovascular sequelae at the 1-yr follow-up. The patient consented to surgical treatment (Institutional Review Board review was not necessary). Used with permission from Barrow Neurological Institute.
Endoscope-Assisted, Transmastoid, High Cervical Approach for Resection of a Jugular Foramen Schwannoma: 2-Dimensional Operative Video
Authors: Mooney Michael A , Almefty Kaith K
Published: June 2019

Jugular foramen schwannomas (JFSs) are relatively rare, benign lesions that account for 10% to 30% of all tumors in the region of the jugular foramen. Given their slow-growing nature, JFSs can become quite large before causing symptoms of lower cranial nerve (LCN) dysfunction, making microsurgical resection a challenge. Successful resection of any JFS is dependent on the identification and preservation of the adjacent, uninvolved LCNs to alleviate nerve compression and preserve function. We report a transmastoid, high cervical approach to a dumbbell-shaped, extracranial JFS that was causing symptomatic LCN compression. The patient presented with dysphagia and was found to have left vocal cord paralysis on video laryngoscopy and intermittent aspiration on a swallowing evaluation. The transmastoid, high cervical exposure allowed for early identification of the tumor as well as the adjacent LCNs. Neurophysiological monitoring included somatosensory evoked potentials; brainstem auditory evoked responses; and cranial nerve VII, X, XI, and XII electromyographic monitoring. Endoscopic assistance allowed for improved LCN visualization from the high cervical exposure and gross-total resection of the tumor. The patient's dysphagia improved both subjectively and objectively following the resection. The patient gave written informed consent for surgery and publication of the case report. Institutional review board approval was not required for this case report. Used with permission from Barrow Neurological Institute.
Editing for Expansion: Railroad Photography, Native Peoples, and the American West, 1860–1880
Authors: Link Alessandra
Published: June 2019

In the nineteenth century, both railroad expansion and photography influenced relations between the United States and Native peoples in powerful ways. Scholars have often dealt with these two technological developments separately, but photographs and railroads have a shared history. Throughout the mid-to-late nineteenth century railroad companies engaged with photographs and photographers to promote travel on their lines. This article evaluates the production and circulation of transcontinental railroad photographs, and it concludes that the so-called golden age of landscape photography was built on the suppression of peopled scenes in the West. Images of Indians and trains that reached broad audiences placed Indigenous peoples in opposition to the modern forces cast in steel and running on steam. Picturing an unpeopled West and anti-modern Indians brightened business prospects for those investing in the promise of U.S. expansion beyond the 100th meridian.
In Vitro and in Planta Evaluation of Trichoderma asperellum TA as a Biocontrol Agent Against Phellinus noxius, the Cause of Brown Root Rot Disease of Trees
Authors: Chou Hao , Xiao Yi-Ting , Tsai Jyh-Nong , Li Ting-Ting , Wu Hung-Yi , Liu Li-yu D. , Tzeng Der-Syh , Chung Chia-Lin
Published: June 2019

Brown root rot (BRR), caused by the white rot fungus Phellinus noxius, is an epidemic disease of diverse broadleaved and coniferous tree species in many tropical and subtropical regions. Flooding and trenching control measures are difficult to implement, and chemical controls can have an adverse impact on ecosystems. Previous studies have provided in vitro evidence for the potential use of Trichoderma spp. for biocontrol of BRR. Here, we analyzed the in vitro antagonistic and mycoparasitic abilities of four Trichoderma spp. isolates against four P. noxius isolates in dual culture and Ficus microcarpa wood blocks. A convenient inoculation system based on root inoculation of a highly susceptible loquat (Eriobotrya japonica) with P. noxius-colonized wheat-oat grains was developed to examine the effect of Trichoderma treatment in planta. Preventive application of Trichoderma asperellum TA, the isolate showing high antagonistic activity in vitro, was effective in preventing and delaying the wilting of P. noxius-inoculated loquat cuttings in greenhouse trials. To understand the specific niche in which T. asperellum TA interacts with P. noxius, KOH-aniline blue fluorescence microscopy was used to investigate the colonization of loquat roots by P. noxius and/or T. asperellum TA. Dilution plating assays were also conducted to quantify Trichoderma populations in the rhizosphere and potting mix. T. asperellum TA was able to robustly establish in the rhizosphere and potting mix but with scarce root penetration limited to the superficial layer. We discuss the timing and strategy for applying antagonistic Trichodema sp. on living trees or in BRR-infested areas for BRR management.
Population Genetic Structure and Cryptic Species of Plasmopara viticola in Australia
Authors: Taylor Andrew S. , Knaus Brian J. , Grünwald Niklaus J. , Burgess Treena
Published: June 2019

Downy mildew of grape caused by Plasmopara viticola is a global pathogen of economic importance to commercial viticulture. In contrast to populations in the northern hemisphere, few studies have investigated the population biology, genetic diversity, and origin of the pathogen in Australian production systems. DNA was extracted from 381 P. viticola samples from Vitis vinifera and alternate hosts collected via fresh and herbarium leaves from populations within Australia and Whatman FTA cards from North America, Brazil, and Uruguay. A total of 32 DNA samples were provided from a French population. The populations were genotyped using 16 polymorphic microsatellite markers. Representative samples from within Australia, Brazil, and Uruguay were also genotyped to determine which of the cryptic species (clades) within the P. viticola species complex were present. Our findings suggest the Australian and South American populations of P. viticola are more closely related to the European population than the North American population, the reported source of origin of the pathogen. The Western Australian population had similarities to the South Australian population, and the tight clustering of samples suggests a single introduction into Western Australia. P. viticola clade aestivalis was the only clade detected in Australian and South American populations. Analysis of the Western Australian population suggests that it is reproducing clonally, but additional research is required to determine the mechanism as to how this is occurring.
Can pathogens optimize both transmission and dispersal by exploiting sexual dimorphism in their hosts?
Authors: Nørgaard Louise Solveig , Phillips Ben L. , Hall Matthew D.
Published: June 2019

Pathogens often rely on their host for dispersal. Yet, maximizing fitness via replication can cause damage to the host and an associated reduction in host movement, incurring a trade-off between transmission and dispersal. Here, we test the idea that pathogens might mitigate this trade-off between reproductive fitness and dispersal by taking advantage of sexual dimorphism in their host, tailoring responses separately to males and females. Using experimental populations of
Daphnia magna
and its bacterial pathogen
Pasteuria ramosa
as a test-case, we find evidence that this pathogen can use male hosts as a dispersal vector, and the larger females as high-quality resource patches for optimized production of transmission spores. As sexual dimorphism in dispersal and body size is widespread across the animal kingdom, this differential exploitation of the sexes by a pathogen might be an unappreciated phenomenon, possibly evolved in various systems.
Inferring
who-infected-whom-where
in the 2016 Zika outbreak in Singapore—a spatio-temporal model
Authors: Prem Kiesha , Lau Max S. Y. , Tam Clarence C. , Ho Marc Z. J. , Ng Lee-Ching , Cook Alex R.
Published: June 2019

Singapore experienced its first known Zika outbreak in 2016. Given the lack of herd immunity, the suitability of the climate for pathogen transmission, and the year-round presence of the vector—
Aedes aegypti
—Zika had the potential to become endemic, like dengue. Guillain–Barré syndrome and microcephaly are severe complications associated elsewhere with Zika and the risk of these complications makes understanding its spread imperative. We investigated the spatio-temporal spread of locally transmitted Zika in Singapore and assessed the relevance of non-residential transmission of Zika virus infections, by inferring the possible infection tree (i.e.
who-infected-whom-where
) and comparing inferences using geographically resolved data on cases' home, their work, or their home and work. We developed a spatio-temporal model using time of onset and both addresses of the Zika-confirmed cases between July and September 2016 to estimate the infection tree using Bayesian data augmentation. Workplaces were involved in a considerable fraction (64.2%) of infections, and homes and workplaces may be distant relative to the scale of transmission, allowing ambulant infected persons may act as the ‘vector’ infecting distant parts of the country. Contact tracing is a challenge for mosquito-borne diseases, but inferring the geographically structured transmission tree sheds light on the spatial transmission of Zika to immunologically naive regions of the country.
The molecular chaperone Hsp33 is activated by atmospheric-pressure plasma protecting proteins from aggregation
Authors: Krewing Marco , Stepanek Jennifer Janina , Cremers Claudia , Lackmann Jan-Wilm , Schubert Britta , Müller Alexandra , Awakowicz Peter , Leichert Lars I. O. , Jakob Ursula , Bandow Julia E.
Published: June 2019

Non-equilibrium atmospheric-pressure plasmas are an alternative means to sterilize and disinfect. Plasma-mediated protein aggregation has been identified as one of the mechanisms responsible for the antibacterial features of plasma. Heat shock protein 33 (Hsp33) is a chaperone with holdase function that is activated when oxidative stress and unfolding conditions coincide. In its active form, it binds unfolded proteins and prevents their aggregation. Here we analyse the influence of plasma on the structure and function of Hsp33 ofEscherichia coliusing a dielectric barrier discharge plasma. While most other proteins studied so far were rapidly inactivated by atmospheric-pressure plasma, exposure to plasma activated Hsp33. Both, oxidation of cysteine residues and partial unfolding of Hsp33 were observed after plasma treatment. Plasma-mediated activation of Hsp33 was reversible by reducing agents, indicating that cysteine residues critical for regulation of Hsp33 activity were not irreversibly oxidized. However, the reduction yielded a protein that did not regain its original fold. Nevertheless, a second round of plasma treatment resulted again in a fully active protein that was unfolded to an even higher degree. These conformational states were not previously observed after chemical activation with HOCl. Thus, although we could detect the formation of HOCl in the liquid phase during plasma treatment, we conclude that other species must be involved in plasma activation of Hsp33.E. colicells over-expressing the Hsp33-encoding genehslOfrom a plasmid showed increased survival rates when treated with plasma while anhslOdeletion mutant was hypersensitive emphasizing the importance of protein aggregation as an inactivation mechanism of plasma.
Nanosecond pulsed electric field induced proliferation and differentiation of osteoblasts and myoblasts
Authors: Vadlamani Ram Anand , Nie Yaohui , Detwiler David A. , Dhanabal Agni , Kraft Alan M. , Kuang Shihuan , Gavin Timothy P. , Garner Allen L.
Published: June 2019

Low-intensity electric fields can induce changes in cell differentiation and cytoskeletal stresses that facilitate manipulation of osteoblasts and mesenchymal stem cells; however, the application times (tens of minutes) are of the order of physiological mechanisms, which can complicate treatment consistency. Intense nanosecond pulsed electric fields (nsPEFs) can overcome these challenges by inducing similar stresses on shorter timescales while additionally inducing plasma membrane nanoporation, ion transport and intracellular structure manipulation. This paper shows that treating myoblasts and osteoblasts with five 300 ns PEFs with intensities from 1.5 to 25 kV cm
−1
increased proliferation and differentiation. While nsPEFs above 5 kV cm
−1
decreased myoblast population growth, 10 and 20 kV cm
−1
trains increased myoblast population by approximately fivefold 48 h after exposure when all cell densities were set to the same level after exposure. Three trials of the PEF-treated osteoblasts showed that PEF trains between 2.5 and 10 kV cm
−1
induced the greatest population growth compared to the control 48 h after treatment. Trains of nsPEFs between 1.5 and 5 kV cm
−1
induced the most nodule formation in osteoblasts, indicating bone formation. These results demonstrate the potential utility for nsPEFs to rapidly modulate stem cells for proliferation and differentiation and motivate future experiments to optimize PEF parameters for
in vivo
applications.
Consensus and polarization in competing complex contagion processes
Authors: Vasconcelos Vítor V. , Levin Simon A. , Pinheiro Flávio L.
Published: June 2019

The rate of adoption of new information depends on reinforcement from multiple sources in a way that often cannot be described by simple contagion processes. In such cases, contagion is said to be complex. Complex contagion happens in the diffusion of human behaviours, innovations and knowledge. Based on that evidence, we propose a model that considers multiple, potentially asymmetric and competing contagion processes and analyse its respective population-wide dynamics, bringing together ideas from complex contagion, opinion dynamics, evolutionary game theory and language competition by shifting the focus from individuals to the properties of the diffusing processes. We show that our model spans a dynamical space in which the population exhibits patterns of consensus, dominance, and, importantly, different types of polarization, a more diverse dynamical environment that contrasts with single simple contagion processes. We show how these patterns emerge and how different population structures modify them through a natural development of spatial correlations: structured interactions increase the range of the dominance regime by reducing that of dynamic polarization, tight modular structures can generate structural polarization, depending on the interplay between fundamental properties of the processes and the modularity of the interaction network.
Automated bioacoustics: methods in ecology and conservation and their potential for animal welfare monitoring
Authors: Mcloughlin Michael P. , Stewart Rebecca , McElligott Alan G.
Published: June 2019

Vocalizations carry emotional, physiological and individual information. This suggests that they may serve as potentially useful indicators for inferring animal welfare. At the same time, automated methods for analysing and classifying sound have developed rapidly, particularly in the fields of ecology, conservation and sound scene classification. These methods are already used to automatically classify animal vocalizations, for example, in identifying animal species and estimating numbers of individuals. Despite this potential, they have not yet found widespread application in animal welfare monitoring. In this review, we first discuss current trends in sound analysis for ecology, conservation and sound classification. Following this, we detail the vocalizations produced by three of the most important farm livestock species: chickens (Gallus gallus domesticus), pigs (Sus scrofa domesticus) and cattle (Bos taurus). Finally, we describe how these methods can be applied to monitor animal welfare with new potential for developing automated methods for large-scale farming.
Sustainable and scalable synthesis of polysubstituted bis-1,2,4-triazoles, bis-2-iminothiazolines and bis-thiobarbiturates using bis-
N
,
N
-disubstituted thioureas as versatile substrate
Authors: Arafa Wael Abdelgayed Ahmed , Ibrahim Hamada Mohamed
Published: June 2019

An expedient and tandem regioselective one-pot protocol for the sono-synthesis of bis-[1,2,4]-triazol-3-yl amines and bis-2-iminothiazolines from corresponding bis-1,3-disubstituted thioureas has been developed. The products' regioselectivity correlate well with the p
K
a
s of the parent amines, in which the amine possessing higher p
K
a
goes to the ring nitrogen, whereas the other nitrogen remains flanked as an exocyclic nitrogen of the bis-triazole or bis-thiazole moieties. Further, the sonochemical preparation of both bis-5-(2-nitrobenzylidene) thiobarbiturates and bis-2-thioxoimidazolidine-4,5-diones from bis-1,3-disubstituted thioureas has also been achieved. The obtained bis-5-(2-nitrobenzylidene)thiobarbiturates easily underwent reductive cyclization to afford the corresponding bis-5-benzo[
c
]isoxazol-3-ylidenethiobarbiturates. The scope and limitations of these strategies have been studied. Moreover, the suggested methodologies have advantages such as broad functional group tolerance, mild conditions, operational simplicity and applicability on a gram scale. Furthermore, the protocols scored well in a number of green metrics, subsequently showing these approaches to be environmentally benign and sustainable processes.
A novel synthetic strategy for styrene–butadiene–styrene tri-block copolymer with high
cis
-1,4 units via changing catalytic active centres
Authors: Liu Jie , Min Xin , Zhang Xuan , Zhu Xiuzhong , Wang Zichao , Wang Tong , Fan Xiaodong
Published: June 2019

A styrene–butadiene–styrene tri-block copolymer (SBS) with a high
cis
-1,4 unit content (greater than 97%) was synthesized by a novel synthetic strategy based on changing the catalytic active centres using
n
-butyllithium and a nickel-based catalyst. Firstly, styrene was polymerized via anionic polymerization using butyllithium as the initiator (Li, activity centre Li) at 50°C. The obtained alkylated macroinitiator (PSLi) was aged with nickel naphthenate (Ni) and boron trifluoride etherate (B) to prepare a second reactive centre (Ni-F), which was used to initiate the polymerization of butadiene (Bd). Finally, triphenyl phosphine (PPh
3
) was added to adjust the electron density of the third active centre (P-Ni-F), and styrene monomer was added again to synthesize the second polystyrene block to obtain SBS. The polymerization technique presented here is simple and has an efficient initiation effect due to the high initiation activities for the different monomers. It also exhibits excellent control over the stereo-structure of the butadiene segments in the prepared copolymers, and the SBS polymers with high
cis
-1,4 unit content were easily achieved.
Some peculiarities of thermopower at the Lifshitz topological transitions due to stacking change in bilayer and multilayer graphene
Authors: Davydov V. N.
Published: June 2019

Singularities of thermopower (the Seebeck coefficient) are considered at the Lifshitz topological transitions (LTT) in bilayer graphene (BLG) and multilayer graphene (MLG) due to stacking change from
AB
to
AA
. The dependence of singularities on
μ
,
γ
1
and
Δ
is investigated (
μ
is the chemical potential,
γ
1
is the interlayer hopping parameter and
Δ
is the gap value) for the gapped graphene, as well as for the gapless one. The present paper results indicate that effects of the thermopower singularities are appreciable and can be used to observe the LTT, and to explore the degree of stacking change from
AB
to
AA
in graphene. Therefore, the thermopower singularities at LTT due to stacking change from
AB
to
AA
can be used as a powerful tool to control electronic properties of BLG- and MLG-based structures.
Endometrial recognition of pregnancy occurs in the grey short-tailed opossum (
Monodelphis domestica
)
Authors: Griffith Oliver W. , Chavan Arun R. , Pavlicev Mihaela , Protopapas Stella , Callahan Ryan , Maziarz Jamie , Wagner Günter P.
Published: June 2019

In human pregnancy, recognition of an embryo within the uterus is essential to support the fetus through gestation. In most marsupials, such as the opossums, pregnancy is shorter than the oestrous cycle and the steroid hormone profile during pregnancy and oestrous cycle are indistinguishable. For these reasons, it was assumed that recognition of pregnancy, as a trait, evolved in the eutherian (placental) stem lineage and independently in wallabies and kangaroos. To investigate whether uterine recognition of pregnancy occurs in species with pregnancy shorter than the oestrous cycle, we examined reproduction in the short-tailed opossum (
Monodelphis domestica
), a marsupial with a plesiomorphic mode of pregnancy. We examined the morphological and gene expression changes in the uterus of females in the non-pregnant oestrous cycle and compared these to pregnancy. We found that the presence of an embryo did not alter some aspects of uterine development but increased glandular activity. Transcriptionally, we saw big differences between the uterus of pregnant and cycling animals. These differences included an upregulation of genes involved in transport, inflammation and metabolic-activity in response to the presence of a fetus. Furthermore, transcriptional differences reflected protein level differences in transporter abundance. Our results suggest that while the uterus exhibits programmed changes after ovulation, its transcriptional landscape during pregnancy responds to the presence of a fetus and upregulates genes that may be essential for fetal support. These results are consistent with endometrial recognition of pregnancy occurring in the opossum. While the effects on maternal physiology appear to differ, recognition of pregnancy has now been observed in eutherian mammals, as well as, Australian and American marsupials.
Concurrent assessment of epidemiological and operational uncertainties for optimal outbreak control: Ebola as a case study
Authors: Li Shou-Li , Ferrari Matthew J. , Bjørnstad Ottar N. , Runge Michael C. , Fonnesbeck Christopher J. , Tildesley Michael J. , Pannell David , Shea Katriona
Published: June 2019

Determining how best to manage an infectious disease outbreak may be hindered by both epidemiological uncertainty (i.e. about epidemiological processes) and operational uncertainty (i.e. about the effectiveness of candidate interventions). However, these two uncertainties are rarely addressed concurrently in epidemic studies. We present an approach to simultaneously address both sources of uncertainty, to elucidate which source most impedes decision-making. In the case of the 2014 West African Ebola outbreak, epidemiological uncertainty is represented by a large ensemble of published models. Operational uncertainty about three classes of interventions is assessed for a wide range of potential intervention effectiveness. We ranked each intervention by caseload reduction in each model, initially assuming an unlimited budget as a counterfactual. We then assessed the influence of three candidate cost functions relating intervention effectiveness and cost for different budget levels. The improvement in management outcomes to be gained by resolving uncertainty is generally high in this study; appropriate information gain could reduce expected caseload by more than 50%. The ranking of interventions is jointly determined by the underlying epidemiological process, the effectiveness of the interventions and the size of the budget. An epidemiologically effective intervention might not be optimal if its costs outweigh its epidemiological benefit. Under higher-budget conditions, resolution of epidemiological uncertainty is most valuable. When budgets are tight, however, operational and epidemiological uncertainty are equally important. Overall, our study demonstrates that significant reductions in caseload could result from a careful examination of both epidemiological and operational uncertainties within the same modelling structure. This approach can be applied to decision-making for the management of other diseases for which multiple models and multiple interventions are available.
Expanding the CRISPR Toolbox with ErCas12a in Zebrafish and Human Cells
Authors: Wierson Wesley A. , Simone Brandon W. , WareJoncas Zachary , Mann Carla , Welker Jordan M. , Kar Bibekananda , Gendron William A. C. , Barry Michael A. , Clark Karl J. , Dobbs Drena L. , McGrail Maura A. , Ekker Stephen C. , Essner Jeffrey J.
Published: June 2019

Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and CRISPR associated (Cas) effector proteins enable the targeting of DNA double-strand breaks (DSBs) to defined loci based on a variable length RNA guide specific to each effector. The guide RNAs are generally similar in size and form, consisting of a ~20 nucleotide sequence complementary to the DNA target and an RNA secondary structure recognized by the effector. However, the effector proteins vary in Protospacer Adjacent Motif (PAM) requirements, nuclease activities, and DNA binding kinetics. Recently, ErCas12a, a new member of the Cas12a family, was identified in Eubacterium rectale. Here, we report the first characterization of ErCas12a activity in zebrafish and human cells. Using a fluorescent reporter system, we show that CRISPR/ErCas12a elicits strand annealing mediated DNA repair more efficiently than CRISPR/Cas9. Further, using our previously reported gene targeting method that utilizes short homology, GeneWeld, we demonstrate the use of CRISPR/ErCas12a to integrate reporter alleles into the genomes of both zebrafish and human cells. Together, this work provides methods for deploying an additional CRISPR/Cas system, thus increasing the flexibility researchers have in applying genome engineering technologies.
Intergenerational transmission of education and ADHD: Effects of parental genotypes
Authors: de Zeeuw Eveline L. , Hottenga Jouke-Jan , Ouwens Klaasjan G. , Dolan Conor V. , Ehli Erik A. , Davies Gareth E. , Boomsma Dorret I. , van Bergen Elsje
Published: June 2019

It is challenging to study whether children resemble their parents due to nature, nurture, or a mixture of both. Here we used a novel design that employs the fact that parents transmit 50% of their alleles to their offspring. The combined effect of these transmitted and non-transmitted alleles on a trait are summarized in a polygenic score (PGS). The non-transmitted PGS can only affect offspring through the environment, via genetically influenced behaviours in the parents, called genetic nurturing. For genotyped mother-father-offspring trios (1,120-2,518 per analysis) we calculated transmitted and non-transmitted PGSs for adult educational attainment (EA) and childhood ADHD and tested if these predicted outcomes in offspring. In adults, both transmitted (R2= 7.6%) and non-transmitted (R2= 1.7%) EA PGSs predicted offspring EA, evidencing genetic nurturing. In children around age 12, academic achievement was predicted only by transmitted EA PGSs (R2= 5.7%), but we did not find genetic nurturing (R2∼ 0.1%). The ADHD PGSs did not significantly predict academic achievement (R2∼ 0.6%). ADHD symptoms in children were predicted by transmitted EA PGSs and ADHD PGSs (R2= 1-2%). Based on these results, we conclude that previously reported associations between parent characteristics and offspring outcomes seem to be mainly a marker of genetic effects shared by parents and children.
Single Cell Profiling Reveals Sex, Lineage and Regional Diversity in the Mouse Kidney
Authors: Ransick Andrew , Lindström Nils O. , Liu Jing , Qin Zhu , Guo Jin-Jin , Alvarado Gregory F. , Kim Albert D. , Black Hannah G. , Kim Junhyong , McMahon Andrew P.
Published: June 2019

Chronic kidney disease affects 10% of the population with notable differences in ethnic and sex-related susceptibility to kidney injury and disease. Kidney dysfunction leads to significant morbidity and mortality, and chronic disease in other organ systems. A mouse organ-centered understanding underlies rapid progress in human disease modeling, and cellular approaches to repair damaged systems. To enhance an understanding of the mammalian kidney, we combined anatomy-guided single cell RNA sequencing of the adult male and female mouse kidney with in situ expression studies and cell lineage tracing. These studies reveal cell diversity and marked sex differences, distinct organization and cell composition of nephrons dependent on the time of nephron specification, and lineage convergence, in which contiguous functionally-related cell types are specified from nephron and collecting system progenitor populations. A searchable database integrating findings to highlight gene-cell relationships in a normal anatomical framework will facilitate study of the mammalian kidney.
Invariance in ecological pattern
Authors: Frank Steven A. , Bascompte Jordi
Published: June 2019

The abundance of different species in a community often follows the log series distribution. Other ecological patterns also have simple forms. Why does the complexity and variability of ecological systems reduce to such simplicity? Common answers include maximum entropy, neutrality, and convergent outcome from different underlying biological processes. This article proposes a more general answer based on the concept of invariance, the property by which a pattern remains the same after transformation. Invariance has a long tradition in physics. For example, general relativity emphasizes the need for the equations describing the laws of physics to have the same form in all frames of reference. By bringing this unifying invariance approach into ecology, we show that the log series pattern dominates when the consequences of processes acting on abundance are invariant to the addition or multiplication of abundance by a constant. The lognormal pattern dominates when the processes acting on net species growth rate obey rotational invariance (symmetry) with respect to the summing up of the individual component processes. Recognizing how these invariances connect pattern to process leads to a synthesis of previous approaches. First, invariance provides a simpler and more fundamental maximum entropy derivation of the log series distribution. Second, invariance provides a simple derivation of the key result from neutral theory: the log series at the metacommunity scale and a clearer form of the skewed lognormal at the local community scale. The invariance expressions are easy to understand because they uniquely describe the basic underlying components that shape pattern.
Neonatal brain-directed gene therapy rescues a mouse model of neurodegenerative CLN6 Batten disease
Authors: Holthaus Sophia-Martha kleine , Martin-Herranz Saul , Massaro Giulia , Aristorena Mikel , Hoke Justin , Hughes Michael P. , Maswood Ryea , Semenyuk Olha , Basche Mark , Shah Amna Z. , Klaska Izabela P. , Smith Alexander J. , Mole Sara E. , Rahim Ahad A , Ali Robin R
Published: June 2019

The neuronal ceroid lipofuscinoses (NCLs), more commonly referred to as Batten disease, are a group of inherited lysosomal storage disorders that present with neurodegeneration, loss of vision and premature death. There are at least 13 genetically distinct forms of NCL. Enzyme replacement therapies and preclinical studies on gene supplementation have shown promising results for NCLs caused by lysosomal enzyme deficiencies. The development of gene therapies targeting the brain for NCLs caused by defects in transmembrane proteins has been more challenging and only limited therapeutic effects in animal models have been achieved so far. Here, we describe the development of an adeno-associated virus (AAV)-mediated gene therapy to treat the neurodegeneration in a mouse model of CLN6 disease, a form of NCL with a deficiency in the membrane-bound protein CLN6. We show that neonatal bilateral intracerebroventricular injections with AAV9 carrying CLN6 increase lifespan by more than 90%, maintain motor skills and motor coordination and reduce neuropathological hallmarks of Cln6-deficient mice up to 23 months post vector administration. These data demonstrate that brain-directed gene therapy is a valid strategy to treat the neurodegeneration of CLN6 disease and may be applied to other forms of NCL caused by transmembrane protein deficiencies in the future.
Novelty gates memory formation through ventro-dorsal hippocampal interaction
Authors: Fredes Felipe , Silva Maria Alejandra , Koppensteiner Peter , Kobayashi Kenta , Joesch Maximilian , Shigemoto Ryuichi
Published: June 2019

Novelty facilitates formation of memories. The detection of novelty and storage of contextual memories are both mediated by the hippocampus, yet the mechanisms that link these two functions remain to be defined. Dentate granule cells (GCs) of the dorsal hippocampus fire upon novelty exposure forming engrams of contextual memory. However, their key excitatory inputs from the entorhinal cortex are not responsive to novelty and are insufficient to make dorsal GCs fire reliably. Here we uncover a powerful glutamatergic pathway to dorsal GCs from ventral hippocampal mossy cells (MCs) that relays novelty, and is necessary and sufficient for driving dorsal GCs activation. Furthermore, manipulation of ventral MCs activity bidirectionally regulates novelty-induced contextual memory acquisition. Our results show that ventral MCs activity controls memory formation through an intra-hippocampal interaction mechanism gated by novelty.
Pyrazinamide triggers degradation of its target aspartate decarboxylase
Authors: Gopal Pooja , Sarathy Jickky , Yee Michelle , Ragunathan Priya , Shin Joon , Bhushan Shashi , Zhu Junhao , Akopian Tatos , Kandror Olga , Lim Teck Kwang , Gengenbacher Martin , Lin Qingsong , Rubin Eric J. , Grüber Gerhard , Dick Thomas
Published: June 2019

The introduction of pyrazinamide (PZA) in the tuberculosis drug regimen shortened treatment from 12 to 6 months 1. PZA is a prodrug that is activated by a Mycobacterium tuberculosis (Mtb) amidase to release its bioactive component pyrazinoic acid (POA) 2. Aspartate decarboxylase PanD, a proenzyme activated by autocatalytic cleavage (Supplementary Fig. 1A, 3) and required for Coenzyme A (CoA) biosynthesis, emerged as a target of POA 4-7. In vitro and in vivo screening to isolate spontaneous POA-resistant Mtb mutants identified missense mutations in either panD or the unfoldase clpC1, encoding a component of the caseinolytic protease ClpC1-ClpP 4,6-9. Overexpression and binding studies of PanD or ClpC1 pointed to PanD as the direct target of POA whereas clpC1 mutations appeared to indirectly cause resistance 4,5,7,9,10. Indeed, supplementing growth media with CoA precursors downstream of the PanD catalyzed step conferred POA resistance 4,7,11. Metabolomic analyses and biophysical studies using recombinant proteins confirmed targeting of PanD by POA 5. However, the exact molecular mechanism of PanD inhibition by POA remained unknown. While most drugs act by inhibiting protein function upon target binding, we show here that POA is not a bona fide enzyme inhibitor. Rather, POA binding to PanD triggers degradation of the protein by ClpC1-ClpP. Thus, the old tuberculosis drug PZA promotes degradation of its target. While novel for an antibacterial, drug-induced target degradation has recently emerged as a strategy in drug discovery across disease indications. Our findings provide the basis for the rational discovery of next generation PZA.
DNA damage response clamp loader Rad24(Rad17) and Mec1(ATR) kinase have distinct functions in regulating meiotic crossovers
Authors: Shinohara Miki , Bishop Douglas K. , Shinohara Akira
Published: June 2019

Crossover (CO) recombination is essential for chromosome segregation during meiosis I. The number and distribution of COs are tightly regulated during meiosis. CO control includes CO assurance and CO interference, which guarantee at least one CO per a bivalent and evenly-spaced CO distribution, respectively. Previous studies showed the role of DNA damage response (DDR) clamp and its loader in efficient formation of meiotic COs by promoting the recruitment of a pro-CO protein Zip3 and interhomolog recombination, and also by suppressing ectopic recombination. In this study, by classical tetrad analysis ofSaccharomyces cerevisiae, we showed that a mutant defective in theRAD24 gene(RAD17in other organisms), which encodes the DDR clamp loader, displayed reduced CO frequencies on two shorter chromosomes (IIIandV) but not on a long chromosome (chromosomeVII). The residual COs in therad24mutant do not show interference. In contrast to therad24mutant, mutants defective in the ATR kinase homolog Mec1/Esr1, including amec1null and amec1kinase-dead mutant, show little or no defect in CO frequency. On the other hand,mec1COs show defects in interference, similar to therad24mutant. Moreover, CO formation and its control are implemented in a chromosome-specific manner, which may reflect a role for chromosome size in regulation.