bluuebunny/crossref_metadata_2025 huggingface dataset:
Spatio-Temporal Modeling and Competition Dynamics in Forest Tillage Experiments on Early Growth of Eucalyptus grandis L.
Authors: González Barrios Pablo , Borges Alejandra , Terra José , Pérez Bidegain Mario , Gutiérrez Lucía
Published: March 2020

Forest tillage experiments regularly use long-term evaluations of large plots creating temporal and/or spatial correlations among observations. Not modeling these correlations could compromise treatment comparisons. The aim of this study was to evaluate the effect of modeling spatio-temporal (ST) variability in forest tillage experiments. We used different strategies that incorporate spatial and/or temporal correlations in the evaluation of tillage intensity effect in initial Eucalyptus growth as well as evaluate the effect of intraplot mortality and competition dynamics. Three tillage intensities in two contrasting soil conditions were compared for tree height and wood volume. Additionally, we compared the use of three individual growth curves for plant height to evaluate the time needed to reach 2 m in height (T2m). We modeled the spatial correlation of T2m using mixed models. In both sites, ST models were superior for plant height and wood volume per hectare, whereas for individual-tree wood volume, temporal models were superior. Pit planting always had a lower performance than disk harrowing and subsoiler, which behaved similarly. The competition dynamics within the plot because of tree mortality was affected by treatments and site. Modeling ST variability is key to improving treatment comparisons in forest experiments.
Generativity in Creative Storytelling: Evidence From a Dementia Care Community
Authors: Kim Seoyoun , Chee Kyong Hee , Gerhart Olga
Published: March 2020

Background and Objectives

Creative group storytelling as utilized in TimeSlips is a social activity that focuses on communication, improvisation, and creativity among its participants with dementia. A collective narrative is a channel through which participants express themselves, and it thus signifies clues about their identities, values, and experiences. No study to date, however, has examined the contents of the stories. Using the generativity model as a theoretical underpinning for analysis, this paper examines the emergent themes of such collective stories.

Research Design and Methods

This study used the data collected in a memory care community where a research team recruited and engaged 21 out of approximately 80 residents with dementia in 6 weekly creative storytelling sessions; 4 small groups of 4 to 6 participants created a total of 24 collective stories. Three researchers analyzed these stories by open-coding emergent themes. Once coded manually, the narratives were managed and analyzed in NVivo.

Results

Consistent with the concept of generativity, a thematic analysis of collective narratives revealed various aspects of participants’ generative concerns. Three themes related to generativity: (1) caring and promoting the well-being of others, (2) family values, and (3) positivity.

Discussion and Implications

The narratives show that participants living with dementia continue to express their generative values and concerns. The findings reveal generative identities held by persons living with dementia, which help destigmatize dementia. The findings also shed light on why creative group storytelling may affect multiple positive outcomes for its participants.
Detecting substrate glycans of fucosyltransferases with fluorophore-conjugated fucose and methods for glycan electrophoresis
Authors: Wu Zhengliang L , Whittaker Mark , Ertelt James M , Person Anthony D , Kalabokis Vassili
Published: March 2020

Like sialylation, fucose usually locates at the nonreducing ends of various glycans on glycoproteins and constitutes important glycan epitopes. Detecting the substrate glycans of fucosyltransferases is important for understanding how these glycan epitopes are regulated in response to different growth conditions and external stimuli. Here we report the detection of these glycans on glycoproteins as well as in their free forms via enzymatic incorporation of fluorophore-conjugated fucose using FUT2, FUT6, FUT7, FUT8 and FUT9. Specifically, we describe the detection of the substrate glycans of these enzymes on fetal bovine fetuin, recombinant H1N1 viral neuraminidase and therapeutic antibodies. The detected glycans include complex and high-mannose N-glycans. By establishing a series of precursors for the synthesis of Lewis X and sialyl Lewis X structures, we not only provide convenient electrophoresis methods for studying glycosylation but also demonstrate the substrate specificities and some kinetic features of these enzymes. Our results support the notion that fucosyltransferases are key targets for regulating the synthesis of Lewis X and sialyl Lewis X structures.
Evaluating the influence of spatially varying catchability on multispecies distribution modelling
Authors: Zhang Chongliang , Chen Yong , Xu Binduo , Xue Ying , Ren Yiping
Published: March 2020

Varying catchability is a common feature in fisheries and has great impacts on fisheries assessments and species distribution models. However, spatial variations in catchability have been rarely evaluated, especially in the multispecies context. We advocate that the need for multispecies models stands for both challenges and opportunities to handle spatial catchability. This study evaluated the influence of spatially varying catchability on the performance of a novel joint species distribution model, namely Hierarchical Modelling of Species Communities (HMSC). We implemented the model under nine simulation scenarios to account for diverse spatial patterns of catchability and conducted empirical tests using survey data from Yellow Sea, China. Our results showed that ignoring variability in catchability could lead to substantial errors in the inferences of species response to environment. Meanwhile, the models’ predictive power was less impacted, yielding proper predictions of relative abundance. Incorporating a spatially autocorrelated structure substantially improved the predictability of HMSC in both simulation and empirical tests. Nevertheless, combined sources of spatial catchabilities could largely diminish the advantage of HMSC in inference and prediction. We highlight situations where catchability needs to be explicitly accounted for in modelling fish distributions, and suggest directions for future applications and development of JSDMs.
The Visual International Relations Project
Authors: Pfonner Michael R , James Patrick
Published: March 2020

International studies, which in the twenty-first century exists as a global, multifaceted and interdisciplinary enterprise, is ready for a turn toward graphic communication. Evidence is mounting that the complexity of international studies is over and beyond what can be managed, intellectually speaking, through an approach that relies overwhelmingly on the exchange of words. Effective communication throughout international studies requires a turn toward graphic means. Thus, the Visual International Relations Project (VIRP) is introduced in this article as a pathway toward more effective conveyance between and among sectors of international studies. Work within the VIRP focuses on creation of an archive that will be available to members of the International Studies Association (ISA).

Work proceeds in six sections. The first section provides an overview of the communication-related challenges facing international studies as scholarship becomes increasingly global in scope and diverse with regard to theorizing and methods applied. Section two makes the case for a visual approach to combat intellectual isolation that is intensifying as a result of communication through words alone. Along with a few alternatives in section three, the foundation for a recommended graphic turn, systemism, is introduced. Systemism emphasizes completeness and visual representation of theorizing. Section four applies a graphic method based on systemism to depict works of scholarship in a common format. Value added from visual representation of these scholarly works is demonstrated in section five, within which communication takes place between and among them. Section six sums up the contributions of the graphic approach based on systemism and explores future directions for research.
Determination of the time-dependent association between ciprofloxacin consumption and ciprofloxacin resistance using a weighted cumulative exposure model compared with standard models
Authors: van Gaalen Rolina D , Altorf-van der Kuil Wieke , Wegdam-Blans Marjolijn C A , Aguilar Diaz Jessica M , Beauchamp Marie-Eve , Chaname Pinedo Linda E , de Greeff Sabine C , Wallinga Jacco
Published: March 2020

Objectives

To obtain comprehensive insight into the association of ciprofloxacin use at different times in the past with the current risk of detecting resistance.

Methods

This retrospective nested case–control study of ciprofloxacin users used Dutch data from the PHARMO Database Network and one laboratory for the period 2003–14. Cases and controls were selected as patients with an antibiotic susceptibility test (AST) indicating ciprofloxacin resistance or susceptibility, respectively. We performed univariable and multivariable conditional logistic regression analyses, defining time-dependent exposure using standard definitions (current ciprofloxacin use, used 0–30, 31–90, 91–180 and 181–360 days ago) and a flexible weighted cumulative effect (WCE) model with four alternative time windows of past doses (0–30, 0–90, 0–180 and 0–360 days).

Results

The study population consisted of 230 cases and 909 controls. Under the standard exposure definitions, the association of ciprofloxacin use with resistance decreased with time [current use: adjusted OR 6.8 (95% CI 3.6–12.4); used 181–360 days ago: 1.3 (0.8–1.9)]. Under the 90 day WCE model (best-fitting model), more recent doses were more strongly associated with resistance than past doses, as was longer or repeated treatment. The 180 day WCE model, which fitted the data equally well, suggested that doses taken 91–180 days ago were also significantly associated with resistance.

Conclusions

The estimates for the association between ciprofloxacin use at different times and resistance show that ciprofloxacin prescribers should consider ciprofloxacin use 0–180 days ago to ensure that patients receive suitable treatment. The OR of ciprofloxacin resistance could be reduced by eliminating repeated ciprofloxacin prescription within 180 days and by treating for no longer than necessary.
Aphid Honeydew Enhances Parasitoid Longevity to the Same Extent as a High-Quality Floral Resource: Implications for Conservation Biological Control of the Wheat Stem Sawfly (Hymenoptera: Cephidae)
Authors: Rand Tatyana A , Waters Debra K
Published: March 2020

Providing sugar resources for parasitoids is an important component of habitat management approaches to bolster biological control. We screened three flowering cover crop species, and one aphid species, for their potential to increase the longevity of the parasitoid wasp, Bracon cephi (Gahan) (Hymenoptera: Braconidae), an important biological control agent of the wheat stem sawfly, Cephus cinctus Norton (Hymenoptera: Cephidae). We found that buckwheat and honeydew from the cereal aphid, Rhopalosiphum padi (Linnaeus) (Hemiptera: Aphididae), increased longevity of B. cephi females by over threefold, while longevity on sunflower and coriander was not significantly different from controls on wheat. The results suggest that incorporating buckwheat into cover crop mixes could enhance parasitoid performance. However, the finding that honeydew associated with a common aphid in wheat provides a suitable resource suggests that a better understanding of the varying quality, and spatial and temporal availability, of aphid honeydew will be a critical consideration in evaluating the potential benefits of managing floral resources for parasitoid conservation in this system.
Bilateral versus unilateral hip arthroscopy for femoroacetabular impingement: a systematic review
Authors: Fernandez Claire E , Morgan Allison M , Sheth Ujash , Tjong Vehniah K , Terry Michael A
Published: March 2020

One in four patients presenting with femoroacetabular impingement (FAI) has bilateral symptoms, and despite excellent outcomes reported after arthroscopic treatment of FAI, there remains a paucity of data on the outcomes following bilateral hip arthroscopy. This systematic review aims to examine the outcomes following bilateral (either ‘simultaneous’ or ‘staged’) versus unilateral hip arthroscopy for FAI. A systematic review of multiple electronic databases was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and checklist. All studies comparing simultaneous, staged and/or unilateral hip arthroscopy for FAI were eligible for inclusion. Case series, case reports and reviews were excluded. All study, patient and hip-specific data were extracted and analyzed. The Newcastle–Ottawa Scale was used to assess study quality. A meta-analysis was not performed due to heterogeneity among outcome measures. A total of six studies, including 722 patients (42.8% male) and 933 hips were eligible for inclusion. The mean age across patients was 35.5. The average time between staged procedures was 7.7 months. Four of the six studies were retrospective cohort studies, while the remaining two were prospective in nature. The overall quality of the eligible studies was found to be good. No significant difference was noted among patient-reported outcomes (modified Harris hip score, hip outcome score and non-arthritic hip score), visual analog scale, return to sport, traction time and complications between those undergoing bilateral (simultaneous or staged) versus unilateral hip arthroscopy. Based on the current available evidence, bilateral hip arthroscopy (whether simultaneous or staged) exhibits similar efficacy and safety when compared with unilateral hip arthroscopy. However, further prospective study is required to confirm this finding.
Experiences and hidden needs of older patients, their families and their physicians in palliative chemotherapy decision-making: a qualitative study
Authors: Tsuboi Rie , Sugishita Mihoko , Hirakawa Yoshihisa , Ando Yuichi
Published: March 2020

Objective

This study aimed to clarify the experiences and hidden needs of older patients with advanced cancer, their families and their physicians in palliative chemotherapy decision-making.

Materials and Methods

We conducted in-depth qualitative individual interviews with content analysis. Patients who were diagnosed as having advanced cancer, were aged ≥70 years (n = 15, median [range] = 77 [70–82] years) and had volunteered to receive palliative chemotherapy within the past 6 months were enrolled. Their families and physicians were also interviewed.

Results

The following four themes were identified: (i) physician’s awareness of paternalism; (ii) readiness for communication of serious news; (iii) spiritual care need assessment and (iv) support as a team. The patients and families expected physicians to demonstrate paternalism in their decision-making because they were unconfident about their self-determination capability. Although the physicians were aware of this expectation, they encountered difficulties in recommending treatment and communicating with older patients. The patients had spiritual pain since the time of diagnosis. Psychological issues were rarely discussed during decision-making and treatment, triggering feelings of isolation in the patients and their families.

Conclusion

Older patients and their families expected a paternalistic approach by the physicians for palliative chemotherapy decision-making. The physicians found it difficult to offer treatment options because of older patient diversity and limitations in evidence-based strategies. Therefore multidisciplinary approaches and evidence-based decision support aids are warranted. Because older patients and their families often have unexpressed psychological burdens including unmet spiritual needs, medical professionals should provide psychological care from the time of diagnosis.
Generation of liver bipotential organoids with a small-molecule cocktail
Authors: Wang Xin , Ni Chao , Jiang Ning , Wei Jinsong , Liang Jianqing , Zhao Bing , Lin Xinhua
Published: March 2020

Understanding the mechanism of how cholangiocytes (liver ductal cells) are activated upon liver injury and specified to hepatocytes would permit liver regenerative medicine. Here we achieved long-term in vitro expansion of mouse liver organoids by modulating signaling pathways with a combination of three small-molecule compounds. CHIR-99021, blebbistatin, and forskolin together maintained the liver organoids in bipotential stage with both cholangiocyte- and hepatocyte-specific gene expression profiles and enhanced capacity for further hepatocyte differentiation. By employing a chemical approach, we demonstrated that Wnt/β-catenin, NMII–Rac, and PKA–ERK are core signaling pathways essential and sufficient for mouse liver progenitor expansion. Moreover, the advanced small-molecule culture of bipotential organoids facilitates the ex vivo investigation of liver cell fate determination and the application of organoids in liver regenerative medicine.
Recent advances in computational methods for measurement of dendritic spines imaged by light microscopy
Authors: Okabe Shigeo
Published: March 2020

Dendritic spines are small protrusions that receive most of the excitatory inputs to the pyramidal neurons in the neocortex and the hippocampus. Excitatory neural circuits in the neocortex and hippocampus are important for experience-dependent changes in brain functions, including postnatal sensory refinement and memory formation. Several lines of evidence indicate that synaptic efficacy is correlated with spine size and structure. Hence, precise and accurate measurement of spine morphology is important for evaluation of neural circuit function and plasticity. Recent advances in light microscopy and image analysis techniques have opened the way toward a full description of spine nanostructure. In addition, large datasets of spine nanostructure can be effectively analyzed using machine learning techniques and other mathematical approaches, and recent advances in super-resolution imaging allow researchers to analyze spine structure at an unprecedented level of precision. This review summarizes computational methods that can effectively identify, segment and quantitate dendritic spines in either 2D or 3D imaging. Nanoscale analysis of spine structure and dynamics, combined with new mathematical approaches, will facilitate our understanding of spine functions in physiological and pathological conditions.
Evaluating Economic Impacts of Prescribed Fire in the Central Hardwood Region
Authors: Mann David P , Wiedenbeck Jan K , Dey Daniel C , Saunders Mike R
Published: March 2020

Surface fires are often prescribed to favor oak (Quercus) regeneration in eastern forests, but there is potential for fire to damage residual overstory timber. This study evaluated the potential economic effects of prescribed fire on sawtimber volume and value across 139 stands, each with a known history of one to six prescribed fires, on the Hoosier, Mark Twain, Wayne, and Daniel Boone National Forests. Sawtimber volume and value losses were highly variable, ranging from 0 to 2,269 bd ft ac–1 and from US$0 to US$272.95 ac–1, respectively, for stands that had received at least one prescribed fire. Volume and value losses increased linearly by +0.9 percent and +1.5 percent per burn, respectively, that a stand received over the past 25 years. Stands with south-facing aspects had greater relative volume and value losses (+1.4 to +1.5 percent, respectively), but this influence was statistically less important than the number of burns in predictive models. The eastern national forests had much lower average relative volume and value losses, <3.0 percent, than the more western Mark Twain National Forest (10–15 percent loss). Species composition affected value loss associated with prescribed fire; red oaks experienced significantly higher value loss than all other species groups.
The Decline of the Clearcut: 26 Years of Change in Silvicultural Practices and Implications in Minnesota
Authors: Windmuller-Campione M A , Russell M B , Sagor E , D’Amato A W , Ek A R , Puettmann K J , Rodman M G
Published: March 2020

Silvicultural decisions and forest-management practices in Minnesota represent the collaboration and partnership between forest managers from multiple organizations and forest researchers. To better understand current practices, trends, needs, and opportunities, Minnesota has invested in the collection of quantitative data on the application of silvicultural systems and forest-management activities in 1991, 1996, 2008, and 2017. Drawing on those data, the goal of our study is to summarize 26 years of data to characterize and quantify trends in forest-management practices. During this period of time, timberland ownership (acres) has increased, whereas harvested volume has decreased (cords). Across state, federal, county, forest industry, and tribal forest lands, which collectively represent the majority of timberlands in Minnesota, the clearcut system decreased from 91% of the harvested area in 1991 to 72 percent in 2017. In contrast, the proportion of total harvested area as part of shelterwood, seed tree, selection, and thinning treatments all more than doubled from 1991 to 2017. Factors influencing the changes relate to forest health and diseases, shifts in ownership structure, and shifts in organizational policy and/or goals. The factors identified mirror many of the trends forest managers are experiencing in other regions, nationally and internationally.
The 3Fs Perfect In Omani Mehri
Authors: Bendjaballah Sabrina , Rubin Aaron D
Published: March 2020

For Antoine Lonnet

In the Mehri language as spoken in Oman, the suffix of the 3fs perfect has the three allomorphs -ōt, -ūt or -ēt. The distribution of these suffixes has never been fully described, in part because, until recently, transcriptions of Mehri often masked the subtle difference between ō and ū. The choice of 3fs suffix depends on the verbal stem and, in some cases, on the nature of certain root consonants. All the 3fs suffixes can be traced to a Proto-Semitic suffix *-at, which has been subjected to several sound rules specific to Omani Mehri, though analogy has also played a role in some verb types.
Social Smoking and French Fancies: The Dublin Art(s) Club, 1886–98
Authors: Milligan Kathryn
Published: March 2020

ABSTRACT

The Dublin Art(s) Club, which operated in the Irish capital from 1886 to 1898, offers an intriguing case study for modes of artistic networks and cultural exchange between Ireland and Britain in the closing decades of the nineteenth century. Despite this, the history of the Club has been little explored in historiography to date, often confused with other ventures by artists in the city. Examining the rise and fall of the Dublin Art(s) Club, along with its members and activities, this article retrieves its history and posits that it offers an example of an aspect of art in Ireland which was conspicuous for its cosmopolitan outlook and active engagement with the wider British art world, which then spanned across both islands. The history of the Dublin Art(s) Club poses a challenge to the extant scholarship of this period in Irish art history, which to date has been largely understood to be focused on themes of national identity, the cultural revival, and artists who left Ireland to train in Belgium and France. This article posits that by re-engaging with the activities of art clubs and societies, a more complex reading of artistic life in Victorian Dublin can emerge.
Virus-induced flowering—a tool for cereals
Authors: Ayre Brian G , El-Gebaly Fathy E , McGarry Roisin C
Published: March 2020

This article comments on:

Yuan C, Li H, Qin C, Zhang X, Chen Q, Zhang P, Xu X, He M, Zhang X, Tör M, Xue Dawei, Wang H, Jackson S, He Y, Liu Y, Shi N, Hong Y. 2020. Foxtail mosaic virus-induced flowering assays in monocot crops. Journal of Experimental Botany 71, 3012–3023.
To TDE or not to TDE: the luminous transient ASASSN-18jd with TDE-like and AGN-like qualities
Authors: Neustadt J M M , Holoien T W-S , Kochanek C S , Auchettl K , Brown J S , Shappee B J , Pogge R W , Dong Subo , Stanek K Z , Tucker M A , Bose S , Chen Ping , Ricci C , Vallely P J , Prieto J L , Thompson T A , Coulter D A , Drout M R , Foley R J , Kilpatrick C D , Piro A L , Rojas-Bravo C , Buckley D A H , Gromadzki M , Dimitriadis G , Siebert M R , Do A , Huber M E , Payne A V
Published: March 2020

We present the discovery of ASASSN-18jd (AT 2018bcb), a luminous optical/ultraviolet(UV)/X-ray transient located in the nucleus of the galaxy 2MASX J22434289–1659083 at z = 0.1192. Over the year after discovery, Swift UltraViolet and Optical Telescope (UVOT) photometry shows the UV spectral energy distribution of the transient to be well modelled by a slowly shrinking blackbody with temperature $T \sim 2.5 \times 10^{4} \, {\rm K}$, a maximum observed luminosity of $L_{\rm max} = 4.5^{+0.6}_{-0.3}\times 10^{44} \, {\rm erg \,s}^{-1}$, and a radiated energy of $E = 9.6^{+1.1}_{-0.6} \times 10^{51} \, {\rm erg}$. X-ray data from Swift X-Ray Telescope (XRT) and XMM–Newton show a transient, variable X-ray flux with blackbody and power-law components that fade by nearly an order of magnitude over the following year. Optical spectra show strong, roughly constant broad Balmer emission and transient features attributable to He ii, N iii–v, O iii, and coronal Fe. While ASASSN-18jd shares similarities with tidal disruption events (TDEs), it is also similar to the newly discovered nuclear transients seen in quiescent galaxies and faint active galactic nuclei (AGNs).
The M dwarf problem: Fe and Ti abundances in a volume-limited sample of M dwarf stars
Authors: Woolf Vincent M , Wallerstein George
Published: March 2020

We report iron and titanium abundance measurements from high-resolution spectra in a volume-limited sample of 106 M0 and M0.5 dwarf stars. The sample includes stars north of the celestial equator and closer than 29 parsecs. The results imply that there is an M dwarf problem similar to the previously known G dwarf problem, in that the fraction of low-metallicity M dwarfs is not large enough to fit simple closed-box models of Galactic chemical evolution. This volume-limited sample avoids many of the statistical uncertainties present in a previous study using a brightness-limited sample of M dwarf stars.
Classification and evolution of galaxies according to the dynamical state of host clusters and galaxy luminosities
Authors: Morell D F , Ribeiro A L B , de Carvalho R R , Rembold S B , Lopes P A A , Costa A P
Published: March 2020

We analyse the dependence of galaxy evolution on cluster dynamical state and galaxy luminosity for a sample of 146 galaxy clusters from the Yang SDSS catalogue. Clusters were split according to their velocity distribution in Gaussians (G) and Non-Gaussians (NG), and further divided by luminosity regime. We performed a classification in the plane of mean stellar age versus specific star formation rate, providing three classes: star-forming (SF), passive (PAS) and intermediate (GV – green valley). We show that galaxies evolve in the same way in G and NG systems, but also suggest that their formation histories lead to different mixtures of galactic types and infall patterns. Separating the GV into star-forming and passive components, we find more bright galaxies in the passive mode of NG systems than in that of G systems. We also find more intermediate faint galaxies in the star-forming component of NG systems than in that of G systems. Our results suggest that GV is the stage where the transition from types Sab and Scd to S0 must be taking place, but the conversion between morphological types is independent of the dynamical stage of the clusters. Analysing the velocity dispersion profiles, we find that objects recently infalling onto clusters have a different composition between G and NG systems. While all galaxy types infall on to G systems, Sab and Scd dominate the infall on to NG systems. Finally, we find that faint Scd galaxies in the outskirts of NG systems present higher asymmetries relative to the mean asymmetry of field galaxies, suggesting that there are environmental effects acting on these objects.
The redshift and the host galaxy of the neutrino candidate 4FGL J0955.1+3551 (3HSP J095507.9+355101)
Authors: Paiano Simona , Falomo Renato , Padovani Paolo , Giommi Paolo , Gargiulo Adriana , Uslenghi Michela , Rossi Andrea , Treves Aldo
Published: March 2020

The BL Lac object 4FGL J0955.1+3551 has been suggested as a possible source of ultra-energetic neutrinos detected by the IceCube observatory. The target was observed in 2020 January at the Large Binocular Telescope. Our spectroscopy (4100–8500 Å) yields a firm redshift z = 0.557 as deduced by the absorption lines of the host galaxy. The upper limit of the minimum equivalent width on emission lines is ∼0.3 Å. From the source image, we are able to resolve the host galaxy for which we measure an absolute magnitude M(R) = −22.9 and Re = 8 kpc, which are values which are typical of the host galaxies of BL Lacs.
Rapid Accumulation of Mutations in Growing Mycelia of a Hypervariable Fungus Schizophyllum commune
Authors: Bezmenova Aleksandra V , Zvyagina Elena A , Fedotova Anna V , Kasianov Artem S , Neretina Tatiana V , Penin Aleksey A , Bazykin Georgii A , Kondrashov Alexey S
Published: March 2020

The basidiomycete Schizophyllum commune has the highest level of genetic polymorphism known among living organisms. In a previous study, it was also found to have a moderately high per-generation mutation rate of 2×10−8, likely contributing to its high polymorphism. However, this rate has been measured only in an experiment on Petri dishes, and it is unclear how it translates to natural populations. Here, we used an experimental design that measures the rate of accumulation of de novo mutations in a linearly growing mycelium. We show that S. commune accumulates mutations at a rate of 1.24×10−7 substitutions per nucleotide per meter of growth, or ∼2.04×10−11 per nucleotide per cell division. In contrast to what has been observed in a number of species with extensive vegetative growth, this rate does not decline in the course of propagation of a mycelium. As a result, even a moderate per-cell-division mutation rate in S. commune can translate into a very high per-generation mutation rate when the number of cell divisions between consecutive meiosis is large.
The Origin of Additive Genetic Variance Driven by Positive Selection
Authors: Liu Li , Wang Yayu , Zhang Di , Chen Zhuoxin , Chen Xiaoshu , Su Zhijian , He Xionglei
Published: March 2020

Fisher’s fundamental theorem of natural selection predicts no additive variance of fitness in a natural population. Consistently, studies in a variety of wild populations show virtually no narrow-sense heritability (h2) for traits important to fitness. However, counterexamples are occasionally reported, calling for a deeper understanding on the evolution of additive variance. In this study, we propose adaptive divergence followed by population admixture as a source of the additive genetic variance of evolutionarily important traits. We experimentally tested the hypothesis by examining a panel of ∼1,000 yeast segregants produced by a hybrid of two yeast strains that experienced adaptive divergence. We measured >400 yeast cell morphological traits and found a strong positive correlation between h2 and evolutionary importance. Because adaptive divergence followed by population admixture could happen constantly, particularly in species with wide geographic distribution and strong migratory capacity (e.g., humans), the finding reconciles the observation of abundant additive variances in evolutionarily important traits with Fisher’s fundamental theorem of natural selection. Importantly, the revealed role of positive selection in promoting rather than depleting additive variance suggests a simple explanation for why additive genetic variance can be dominant in a population despite the ubiquitous between-gene epistasis observed in functional assays.
Adaptive Shifts in Gene Regulation Underlie a Developmental Delay in Thermogenesis in High-Altitude Deer Mice
Authors: Velotta Jonathan P , Robertson Cayleih E , Schweizer Rena M , McClelland Grant B , Cheviron Zachary A
Published: March 2020

Aerobic performance is tied to fitness as it influences an animal’s ability to find food, escape predators, or survive extreme conditions. At high altitude, where low O2 availability and persistent cold prevail, maximum metabolic heat production (thermogenesis) is an aerobic performance trait that is closely linked to survival. Understanding how thermogenesis evolves to enhance survival at high altitude will yield insight into the links between physiology, performance, and fitness. Recent work in deer mice (Peromyscus maniculatus) has shown that adult mice native to high altitude have higher thermogenic capacities under hypoxia compared with lowland conspecifics, but that developing high-altitude pups delay the onset of thermogenesis. This finding suggests that natural selection on thermogenic capacity varies across life stages. To determine the mechanistic cause of this ontogenetic delay, we analyzed the transcriptomes of thermoeffector organs—brown adipose tissue and skeletal muscle—in developing deer mice native to low and high altitude. We demonstrate that the developmental delay in thermogenesis is associated with adaptive shifts in the expression of genes involved in nervous system development, fuel/O2 supply, and oxidative metabolism pathways. Our results demonstrate that selection has modified the developmental trajectory of the thermoregulatory system at high altitude and has done so by acting on the regulatory systems that control the maturation of thermoeffector tissues. We suggest that the cold and hypoxic conditions of high altitude force a resource allocation tradeoff, whereby limited energy is allocated to developmental processes such as growth, versus active thermogenesis, during early development.
OLGenie: Estimating Natural Selection to Predict Functional Overlapping Genes
Authors: Nelson Chase W , Ardern Zachary , Wei Xinzhu
Published: March 2020

Purifying (negative) natural selection is a hallmark of functional biological sequences, and can be detected in protein-coding genes using the ratio of nonsynonymous to synonymous substitutions per site (dN/dS). However, when two genes overlap the same nucleotide sites in different frames, synonymous changes in one gene may be nonsynonymous in the other, perturbing dN/dS. Thus, scalable methods are needed to estimate functional constraint specifically for overlapping genes (OLGs). We propose OLGenie, which implements a modification of the Wei-Zhang method. Assessment with simulations and controls from viral genomes (58 OLGs and 176 non-OLGs) demonstrates low false positive rates and good discriminatory ability in differentiating true OLGs from non-OLGs. We also apply OLGenie to the unresolved case of HIV-1’s putative antisense protein gene, showing significant purifying selection. OLGenie can be used to study known OLGs and to predict new OLGs in genome annotation. Software and example data are freely available at https://github.com/chasewnelson/OLGenie.
Loci specific epigenetic drug sensitivity
Authors: Zhang Thanutra , Pilko Anna , Wollman Roy
Published: March 2020

Therapeutic targeting of epigenetic modulators offers a novel approach to the treatment of multiple diseases. The cellular consequences of chemical compounds that target epigenetic regulators (epi-drugs) are complex. Epi-drugs affect global cellular phenotypes and cause local changes to gene expression due to alteration of a gene chromatin environment. Despite increasing use in the clinic, the mechanisms responsible for cellular changes are unclear. Specifically, to what degree the effects are a result of cell-wide changes or disease related locus specific effects is unknown. Here we developed a platform to systematically and simultaneously investigate the sensitivity of epi-drugs at hundreds of genomic locations by combining DNA barcoding, unique split-pool encoding, and single cell expression measurements. Internal controls are used to isolate locus specific effects separately from any global consequences these drugs have. Using this platform we discovered wide-spread loci specific sensitivities to epi-drugs for three distinct epi-drugs that target histone deacetylase, DNA methylation and bromodomain proteins. By leveraging ENCODE data on chromatin modification, we identified features of chromatin environments that are most likely to be affected by epi-drugs. The measurements of loci specific epi-drugs sensitivities will pave the way to the development of targeted therapy for personalized medicine.
Highlights of the 2019 Society for Neuro-Oncology Inaugural Brain Metastases Conference: establishing a dedicated meeting to address an unmet need in the field
Authors: Zuccato Jeffrey A , Aizer Ayal A , Lee Eudocia Quant , Ahluwalia Manmeet S , O’Halloran Philip J , Mansouri Alireza , Wen Patrick Y , Zadeh Gelareh
Published: March 2020

Brain metastases comprise the majority of central nervous tumors in adults and confer poorer survival for patients with primary cancer. Systemic disease control is improving with advances in treatment for primary tumors and the complexity of brain metastases management is increasing with multimodality approaches incorporating combinations of surgery, radiotherapy, chemotherapy, targeted therapies, and immunotherapy. Accordingly, the Society for Neuro-Oncology established an annual brain metastases conference to unite colleagues from multiple disciplines with content spanning a range of timely topics relevant to improving our understanding of brain metastases and how they are optimally treated. The inaugural meeting on August 16–17, 2019 was very successful with 163 impactful presentations being delivered to a large multidisciplinary audience on current research advances in the field of neuro-oncology. This review summarizes the major themes of the meeting and highlights the main findings presented.
Interferon-β exposure induces a fragile glioblastoma stem cell phenotype with a transcriptional profile of reduced migratory and MAPK pathway activity
Authors: Lohmann Birthe , Silginer Manuela , Picard Daniel , Schneider Hannah , Remke Marc , Roth Patrick , Reifenberger Guido , Weller Michael
Published: March 2020

Background

Type I interferons (IFN-α/β) are cytokines that are typically expressed in response to double-stranded RNA associated with viral infections. Glioblastomas are the most common malignant primary brain tumors, characterized by an infiltrative growth pattern and prominent angiogenic activity, and thought to be maintained by a subpopulation of glioma-initiating (stem-like) cells (GICs). The growth of human GIC lines is highly sensitive to IFN-β.

Methods

Repetitive pulse stimulation with IFN-β1a (IS) was used to generate IS sublines that had acquired resistance to IFN-β-induced suppression of sphere formation. These cell lines were characterized by analyses of type 1 IFN signaling, growth patterns, and transcriptomic profiles.

Results

Here we report that repetitive IFN-β1a stimulation (IS) induces a stable phenotype (referred to as IS) at the level of maintaining sphere formation, although classical IFN signaling defined by the expression of both IFN receptors, myxovirus resistance protein A (MxA) accumulation, and STAT1 induction is unaffected. Furthermore, this stably altered IS phenotype is characterized by constitutively decreased sphere formation capacity and morphological features of senescence and autophagy. Transcriptional profiling reveals increased type I IFN signaling in these IS cells, but decreased expression of genes involved in receptor signaling and cell migration.

Conclusions

Altogether, these data suggest a role for promoting IFN-β signaling in glioblastoma and might provide clues to design future therapeutic approaches.
High Carriage Rates of Multidrug-Resistant Gram-Negative Bacteria in Neonatal Intensive Care Units From Ghana
Authors: Labi Appiah-Korang , Bjerrum Stephanie , Enweronu-Laryea Christabel C , Ayibor Prosper K , Nielsen Karen L , Marvig Rasmus L , Newman Mercy J , Andersen Leif P , Kurtzhals Jorgen A L
Published: March 2020

Background

Carriage of multidrug resistant (MDR) Gram-negative bacteria (GN) in hospitalized neonates may increase the risk of difficult-to-treat invasive infections at neonatal intensive care units (NICUs). Data on MDRGN carriage among hospitalized newborns in Africa are limited.

Methods

We conducted a cross-sectional study at the NICUs of 2 tertiary hospitals in Ghana. Swabs from the axilla, groin, perianal region, and the environment were cultured, GN were identified, and antibiotic susceptibility was tested. We obtained blood culture isolates from neonates with sepsis. Whole-genome sequencing was used to characterize carbapenemase-producing Klebsiella pneumoniae. Typing was done by multilocus sequence typing (MLST) and single nucleotide polymorphism (SNP) analysis.

Results

A total of 276 GN were isolated from 228 screened neonates. Pathogenic GN were cultured in 76.8% (175 of 228) of neonates. Klebsiella spp (41.7%; 115 of 276) and Escherichia coli (26.4%; 73 of 276) were the commonest organisms. Carriage rates of MDRGN and third-generation cephalosporin resistant organisms were 49.6% (113 of 228) and 46.1% (105 of 228), respectively. Among Klebsiella spp, 75.6% (87 of 115) phenotypically expressed extended-spectrum β-lactamase activity, whereas 15.6% expressed carbapenemase and harbored bla-OXA-181 and bla-CTX-M-15. Overall, 7.0% (16 of 228) of neonates developed GN bloodstream infection. In 2 of 11 neonates, sequencing showed the same identity between carriage and the bloodstream isolate. Length of stay before specimen collection and antibiotic use were independently associated with carriage rates, which increased from 13% at admission to 42% by day 2 and reached a plateau at 91% by day 15.

Conclusions

High carriage rates of MDRGN, including carbapenemase-producing enterobacterales may be an emerging problem in NICUs in Africa.
Risk Factors for Positive Follow-Up Blood Cultures in Gram-Negative Bacilli Bacteremia: Implications for Selecting Who Needs Follow-Up Blood Cultures
Authors: Mitaka Hayato , Gomez Tessa , Lee Young Im , Perlman David C
Published: March 2020

Background

The value of follow-up blood cultures (FUBCs) to document clearance of bacteremia due to Gram-negative bacilli (GNB) has not been well established. Although previous studies suggested that the yield of FUBCs for GNB bacteremia is low, it remains to be elucidated for whom FUBC may be beneficial and for whom it is unnecessary.

Methods

A retrospective cohort study was performed at 4 acute care hospitals to identify risk factors for positive FUBCs with GNB bacteremia and to better guide clinicians’ decisions as to which patients may or may not benefit from FUBCs. Participants included adult patients with GNB bacteremia who had FUBCs and were admitted between January 2017 and December 2018. The primary outcomes were the factors associated with positive FUBCs and the yield of FUBCs with and without the factors.

Results

Of 306 patients with GNB bacteremia who had FUBCs, 9.2% (95% confidence interval, 6.2%–13.0%) had the same GNB in FUBCs. In the multivariate logistic regression analysis, end-stage renal disease on hemodialysis, intravascular device, and bacteremia due to extended-spectrum β-lactamase or carbapenemase-producing organism were identified as independent predictors of positive FUBCs with GNB bacteremia. Approximately 7 FUBCs and 30 FUBCs were needed for patients with ≥1 or no risk factors, respectively, to yield 1 positive result.

SummaryThis multi-site retrospective cohort study found that among patients with gram-negative bacilli (GNB) bacteremia, having ESRD on hemodialysis, intravascular devices, or bacteremia due to multi-drug resistant GNB were each independently associated with having a positive follow-up blood culture.

Conclusions

Follow-up blood culture may not be necessary for all patients with GNB bacteremia and has the highest yield in patients with 1 or more risk factors.
Institutional ownership and governance
Authors: Franks Julian
Published: March 2020

This paper describes different forms of ownership across countries and how these forms influence the way companies are governed. In most stock markets in the world, listed companies frequently have a controlling shareholder, usually a family. However, Japan, the UK, and to a lesser extent the US, are exceptions. In these three countries, ownership is frequently highly fragmented, where share stakes are held by different institutional owners, including asset managers, both active and passive, and by shareholder activists. The paper focuses in particular on the governance structure of different institutional shareholders, how they engage with target firms, and their effectiveness. The paper concludes with recommendations for regulators to enhance different forms of ownership.
The Ottoman Postmaster: Contractors, Communication and Early Modern State Formation*
Authors: Koh Choon Hwee
Published: March 2020

Prevailing historiography views the use of contractors by states as indicative of a loss or decentralization of power. This article takes the case of the Ottoman postmaster to demonstrate how contracting could in fact strengthen early modern empires and to argue that the binary spatial metaphors of ‘centralization’ and ‘decentralization’ cannot adequately explain how power worked in the early modern world (about 1500–1800). Indeed, recent scholarship has highlighted the scale and significance of military contractors in early modern European warfare. However, contractors were not confined to expanding military capacity; they were also employed to expand administrative capacity in diverse arenas. Evidence from Ottoman fiscal documents and judicial registers shows how contracted postmasters played a crucial role in strengthening the imperial bureaucracy’s supervision of a sprawling postal system. In contrast to war-making, which involved the short-term mobilization of vast resources, maintaining a large-scale infrastructure required long-term co-ordination across multiple dispersed nodes, and this entailed a different spatial configuration of power that disrupts the dichotomous paradigm of centralization and decentralization. Ultimately, a holistic appraisal of early modern state-building needs to consider not just cases of war-making or provincial administration, but also pan-imperial infrastructures like information and communication systems.