bluuebunny/crossref_metadata_2025 huggingface dataset:
Prehistoric and Traditional Agriculture in Lowland Mesoamerica
Authors: Cagnato Clarissa
Published: February 2019

Mesoamerica is one of the world’s primary centers of domestication where agriculture arose independently. Paleoethnobotany (or archaeobotany), along with archaeology, epigraphy, and ethnohistorical and ethnobotanical data, provide increasingly important insights into the ancient agriculture of Lowland Mesoamerica (below 1000 m above sea level). Moreover, new advances in the analysis of microbotanical remains in the form of pollen, phytoliths, and starch-grain analysis and chemical analysis of organic residues have further contributed to our understanding of ancient plant use in this region. Prehistoric and traditional agriculture in the lowlands of Mesoamerica—notably the Maya lowlands, the Gulf Coast, and the Pacific Coast of southern Chiapas (Mexico) and Guatemala—from the Archaic (ca. 8000/7000–2000 bc) through the Preclassic/Formative (2000 bc–ad 250) and into the Classic (ad 250–900) period, are covered. During the late Archaic, these lowland regions were inhabited by people who took full advantage of the rich natural biodiversity but also grew domesticates before becoming fully sedentary. Through time, they developed diverse management strategies to produce food, from the forest management system (which includes swidden agriculture), to larger scale land modifications such as terraces, and continued to rely on semidomesticated and wild plant resources. Although lowland populations came to eventually rely on maize as a staple, other resources such as root crops and fruit trees were also cultivated, encouraged, and consumed. The need for additional research that includes systematic collection of paleoethnobotanical data, along with other lines of evidence, will be key to continue refining the understanding of ancient subsistence systems and how these changed through time and across lowland Mesoamerica.
Indigenous American Agricultural Contributions to Modern Global Food Systems
Authors: Bruno Maria C.
Published: February 2019

World food systems in the 21st century comprise domesticated plant and animal species that originated from nearly every continent on the globe, spread through exchange and trade, and have been taken up by farmers and cooks worldwide. The indigenous inhabitants of the Americas domesticated several of the worlds’ most important food crops, including maize, potatoes, chili peppers, and quinoa. They also domesticated several animal species, two of which, llamas and alpacas, have become important as alternative herd animals outside of their native Andes. While maize, potatoes, and chili peppers became important globally in the 16th and 17th centuries as part of the Columbian Exchange, llamas/alpacas and quinoa have only gained worldwide prominence in the 20th and 21st centuries.

Unraveling the history of how, where, when, and why these species were domesticated requires the expertise of researchers in the fields of biology, genetics, and archaeology. Domestication is the process by which humans transform wild plant or animal populations into forms that can only be maintained with human intervention. Humans build upon the natural variation in these species but select traits that while desirable for humans, would not be beneficial to survival without them. Using a range of evidence from the remains of ancient plants and animals recovered from archaeological sites to the study of the genetic relationships of living and ancient plant and animal populations, these researchers are revealing how ancient American populations created some of the world’s most important food sources.
What Is Public and What Is Private in Water Provision: Insights from 19th-Century Philadelphia, Boston, and New York
Authors: Malin Gwynneth C.
Published: February 2019

Water became the first public utility in the United States. Before public transportation and public regulation of utilities like electricity and gas, North American cities adopted public water, but this transition is a relatively recent phenomenon. Until the 1830s, both water supply and sewerage were seen as private entities to be managed by private companies and private individuals with nominal assistance from local governments. Water provision was often a blend of public and private efforts, and if residents wanted a well or a sewer built in their neighborhood, they had to help pay for it. Until the mid-19th century, residents of Northeast U.S. cities drew water for domestic uses from local ponds, rivers, and groundwater sources. At this time, procuring water was a daily activity for residents that was linked to economic class.

The 19th century was a key period in the redefinition of water as a public-sector responsibility in the United States. The cities of Philadelphia, Boston, and New York illustrate this change. City officials made the gradual transition from relying on private water companies to implementing public management of the water supply. As increasing urbanization and growing immigrant populations rendered local and privately managed water sources undersupplied, elected officials began to search for new sources of water located beyond city limits. Philadelphia was the first to transition to public water management in 1801, followed by New York in 1842, and Boston in 1848. While each city’s history is unique, city officials took similar approaches to defining public and private with regard to water provision by gradually eliminating private water companies and by increasing funding for public works. Common themes included water pollution, the need to tap new water supplies further from the city centers, disease prevention, fire protection, and financial corruption, within both private water companies and municipal efforts to supply water. While most cities of the Northeast United States transitioned to municipal operation of water supply during the 19th century, the shift was not without its challenges and complexities. Funding shortages often prevented change, but crises, such as fire, drought, and infectious disease outbreaks, forced the hands of municipal officials. Timelines to public water varied. While Boston and Philadelphia achieved permanent public water in the early 19th century, New York experienced a longer trajectory. In each case, public management of water definitively triumphed over private. By the early 20th century, urban Americans conceptualized public and private differently than they had during the 19th century. Water management was at the center of this profound shift.
School Social Work in Charter Schools
Authors: Dupper David , Jones Aubrey
Published: February 2019

Charter schools were founded as a new kind of public school that valued integration, autonomy, and innovation. However, the overall performance of charter schools has been mixed. While positive findings related to the performance of charter schools have been reported, a number of controversial issues and practices involving charter schools have also been identified in the literature. As the number of charter schools continues to grow, the demand for school social work practice in charter schools will also increase. Since a major focus of school social work practice is serving and advocating for at-risk students and their families, this article highlights several issues that have particular relevance for school social work practice serving at-risk students and their families in charter schools and proposes interventions designed to assist at-risk students and their families. These issues are: assisting parents of at-risk students with the application process, advocating for practices to enhance the long-term academic achievement of at-risk students, and equipping at-risk students with skills to meet the behavioral demands of “no excuses” charter schools.
Financial Inclusion and Financial Access
Authors: Birkenmaier Julie , Despard Mathieu , Friedline Terri , Huang Jin
Published: February 2019

Financial inclusion, the goal of financial access, broadly refers to the ability of all people in a society to access and be empowered to use safe, affordable, relevant, and convenient financial products and services for achieving their goals. Financial inclusion promotes household and societal financial well-being and requires access to an array of financial products and services such as savings accounts, credit cards, mortgage and small business loans, and small-dollar consumer loans. Despite the advantages, too many individuals and households lack financial inclusion and access by being unbanked, underbanked, and/or they are forced to use alternative financial services. Achieving financial inclusion will require participation from many different types of formal financial institutional actors, such as banks, credit unions, community development financial institutions, and national credit bureaus. Social work assists to build financial inclusion and access through practice innovations, research, and policy advocacy.
DIFFpop: a stochastic computational approach to simulate differentiation hierarchies with single cell barcoding
Authors: Ferlic Jeremy , Shi Jiantao , McDonald Thomas O , Michor Franziska
Published: February 2019

DIFFpop is an R package designed to simulate cellular differentiation hierarchies using either exponentially-expanding or fixed population sizes. The software includes functionalities to simulate clonal evolution due to the emergence of driver mutations under the infinite-allele assumption as well as options for simulation and analysis of single cell barcoding and labeling data. The software uses the Gillespie Stochastic Simulation Algorithm and a modification of expanding or fixed-size stochastic process models expanded to a large number of cell types and scenarios.

Availability and implementation

DIFFpop is available as an R-package along with vignettes on Github (https://github.com/ferlicjl/diffpop).

Supplementary information

Supplementary data are available at Bioinformatics online.
metagenomeFeatures: an R package for working with 16S rRNA reference databases and marker-gene survey feature data
Authors: Olson Nathan D , Shah Nidhi , Kancherla Jayaram , Wagner Justin , Paulson Joseph N , Corrada Bravo Hector
Published: February 2019

We developed the metagenomeFeatures R Bioconductor package along with annotation packages for three 16S rRNA databases (Greengenes, RDP and SILVA) to facilitate working with 16S rRNA databases and marker-gene survey feature data. The metagenomeFeatures package defines two classes, MgDb for working with 16S rRNA sequence databases, and mgFeatures for marker-gene survey feature data. The associated annotation packages provide a consistent interface to the different databases facilitating database comparison and exploration. The mgFeatures-class represents a crucial step in the development of a common data structure for working with 16S marker-gene survey data in R.

Availability and implementation

https://bioconductor.org/packages/release/bioc/html/metagenomeFeatures.html.

Supplementary information

Supplementary material is available at Bioinformatics online.
FORESEE: a tool for the systematic comparison of translational drug response modeling pipelines
Authors: Turnhoff Lisa-Katrin , Hadizadeh Esfahani Ali , Montazeri Maryam , Kusch Nina , Schuppert Andreas
Published: February 2019

Translational models that utilize omics data generated in in vitro studies to predict the drug efficacy of anti-cancer compounds in patients are highly distinct, which complicates the benchmarking process for new computational approaches. In reaction to this, we introduce the uniFied translatiOnal dRug rESponsE prEdiction platform FORESEE, an open-source R-package. FORESEE not only provides a uniform data format for public cell line and patient datasets, but also establishes a standardized environment for drug response prediction pipelines, incorporating various state-of-the-art pre-processing methods, model training algorithms and validation techniques. The modular implementation of individual elements of the pipeline facilitates a straightforward development of combinatorial models, which can be used to re-evaluate and improve already existing pipelines as well as to develop new ones.

Availability and implementation

FORESEE is licensed under GNU General Public License v3.0 and available at https://github.com/JRC-COMBINE/FORESEE and https://doi.org/10.17605/OSF.IO/RF6QK, and provides vignettes for documentation and application both online and in the Supplementary Files 2 and 3.

Supplementary information

Supplementary data are available at Bioinformatics online.
Sperm selection methods in the 21st century
Authors: Vaughan Denis A , Sakkas Denny
Published: February 2019

Natural sperm selection in humans is a rigorous process resulting in the highest quality sperm reaching, and having an opportunity to fertilize, the oocyte. Relative to other mammalian species, the human ejaculate consists of a heterogeneous pool of sperm, varying in characteristics such as shape, size, and motility. Semen preparation in assisted reproductive technologies (ART) has long been performed using either a simple swim-up method or density gradients. Both methodologies provide highly motile sperm populations; however neither replicates the complex selection processes seen in nature. A number of methods have now been developed to mimic some of the natural selection processes that exist in the female reproductive tract. These methods attempt to select a better individual, or population of, spermatozoa when compared to classical methods of preparation. Of the approaches already tested, platforms based upon sperm membrane markers, such as hyaluronan or annexin V, have been used to either select or deselect sperm with varied success. One technology that utilizes the size, motility, and other characteristics of sperm to improve both semen analysis and sperm selection is microfluidics. Here, we sought to review the efficacy of both available and emerging techniques that aim to improve the quality of the sperm pool available for use in ART.
The Unsolved Link of Genetic Markers and Crohn’s Disease Progression: A North American Cohort Experience
Authors: O’Donnell Sarah , Borowski Krzysztof , Espin-Garcia Osvaldo , Milgrom Raquel , Kabakchiev Boyko , Stempak Joanne , Panikkath Deepah , Eksteen Bertus , Xu Wei , Steinhart A Hillary , Kaplan Gilaad G , McGovern Dermot P B , Silverberg Mark S
Published: February 2019

Background

While progress has been made in the identification of Crohn’s disease (CD) susceptibility loci, efforts to identify a genetic basis for disease progression have been less fruitful. The specific aim of this study was to build upon the major genetic advances made in IBD by applying genome-wide technologies toward predicting disease progression in CD.

Methods

Crohn’s disease cases (n = 1495) from 3 IBD centers were reviewed by experienced physicians. Clinical and demographic details were collected, focusing on the time to first disease progression. Genome-wide association (GWA) analysis was carried out on 3 clinical outcomes: 1) time to disease progression; 2) time to first abdominal surgery; and 3) a binary analysis of indolent vs progressive disease. Cox-proportional hazard and logistic regression models were used.

Results

A GWA analysis was carried out to determine any genetic variation associated with the time to disease progression; 662 cases were included after quality control (QC) and exclusion of any cases with B2/B3 behavior at baseline (n = 450). There were 1360 cases included after QC in the time to abdominal surgery analysis. No variant reached genome-wide significance in any of the 3 analyses performed. Eight known IBD susceptibility single nucleotide polymorphism (SNPs) were found to be associated with time-to-abdominal surgery SMAD3 (rs17293632), CCR6 (rs1819333), CNTF (rs11229555), TSPAN14 (rs7097656), CARD9 (rs10781499), IPMK (rs2790216), IL10 (rs3024505), and SMURF1 (rs9297145) (P < 0.05).

Conclusion

Our GWA study failed to show any SNP-phenotype association reaching genome-wide significance. It is likely that multiple variables affect disease progression, with genetic factors potentially having only a small effect size.
Solitary, Well-Circumscribed, T2 Hyperintense Masses on MRI Have Very Low Malignancy Rates
Authors: Grimm Lars J , Enslow Michael , Ghate Sujata V
Published: February 2019

Objective

The purpose of this study was to determine the malignancy rate of solitary MRI masses with benign BI-RADS descriptors.

Methods

A retrospective review was conducted of all breast MRI reports that described a mass with a final BI-RADS assessment of 3, 4, or 5, from February 1, 2005, through February 28, 2014 (n = 1510). Studies were excluded if the mass was not solitary, did not meet formal criteria for a mass, or had classically suspicious BI-RADS features (e.g., washout kinetics, and spiculated margin). The masses were reviewed by 2 fellowship-trained breast radiologists who reported consensus BI-RADS mass margin, shape, internal-enhancement, and kinetics descriptors. The T2 signal was reported as hyperintense if equal to or greater than the signal intensity of the axillary lymph nodes. Pathology results or 2 years of imaging follow-up were recorded. Comparisons were made between mass descriptors and clinical outcomes.

Results

There were 127 women with 127 masses available for analysis. There were 76 (60%) masses that underwent biopsy for an overall malignancy rate of 4% (5/127): 2 ductal carcinoma in situ (DCIS) and 3 invasive ductal carcinoma. The malignancy rate was 2% (1/59) for T2 hyperintense solitary masses. The malignancy rate was greater than 2% for all of the following BI-RADS descriptors: oval (3%, 3/88), round (5%, 2/39), circumscribed (4%, 5/127), homogeneous (4%, 3/74), and dark internal septations (4%, 2/44).

Conclusion

T2 hyperintense solitary masses without associated suspicious features have a low malignancy rate, and they could be considered for a BI-RADS 3 final assessment.
Divergent Switchgrass Cultivars Modify Cereal Aphid Transcriptomes
Authors: Koch Kyle G , Scully Erin D , Palmer Nathan A , Geib Scott M , Sarath Gautam , Heng-Moss Tiffany , Bradshaw Jeffrey D
Published: February 2019

Schizaphis graminum Rondani (Hemiptera: Aphididae) and Sipha flava Forbes (Hemiptera: Aphididae) are two common pests of bioenergy grasses. Despite the fact that they are both considered generalists, they differ in their ability to colonize Panicum virgatum cultivars. For example, S. flava colonizes both P. virgatum cv. Summer and P. virgatum cv. Kanlow whereas S. graminum can only colonize Summer. To study the molecular responses of these aphids to these two switchgrass cultivars, we generated de novo transcriptome assemblies and compared the expression profiles of aphids feeding on both cultivars to profiles associated with feeding on a highly susceptible sorghum host and a starvation treatment. Transcriptome assemblies yielded 8,428 and 8,866 high-quality unigenes for S. graminum and S. flava, respectively. Overall, S. graminum responded strongly to all three treatments after 12 h with an upregulation of unigenes coding for detoxification enzymes while major transcriptional changes were not observed in S. flava until 24 h. Additionally, while the two aphids responded to the switchgrass feeding treatment by downregulating unigenes linked to growth and development, their responses to Summer and Kanlow diverged significantly. Schizaphis graminum upregulated more unigenes coding for stress-responsive enzymes in the Summer treatment compared to S. flava; however, many of these unigenes were actually downregulated in the Kanlow treatment. In contrast, S. flava appeared capable of overcoming host defenses by upregulating a larger number of unigenes coding for detoxification enzymes in the Kanlow treatment. Overall, these findings are consistent with previous studies on the interactions of these two cereal aphids to divergent switchgrass hosts.
Comment on: Price Discovery in High Resolution
Authors: de Jong Frank
Published: February 2019

This note is a summary of my discussion of Joel Hasbrouck’s keynote paper at the 2018 Society for Financial Econometrics conference.
A GMM Skewness and Kurtosis Ratio Test for Higher Moment Dependence
Authors: Wong Woon K
Published: February 2019

This article extends the variance ratio test of Lo and MacKinlay (1988) to tests of skewness and kurtosis ratios using the generalized methods of moments. In particular, overlapping observations are used in which dependencies are explicitly modeled to make the tests more powerful and have better size properties. The proposed higher-order ratio tests can be useful in risk management where risk models are estimated using daily data but multiperiod forecasts of tail risks are required for the determination of risk capital. Application of the tests finds significant higher moment dependence in the U.S. stock market returns.
Mapping structure and morphology of amorphous organic thin films by 4D-STEM pair distribution function analysis
Authors: Mu Xiaoke , Mazilkin Andrey , Sprau Christian , Colsmann Alexander , Kübel Christian
Published: February 2019

Imaging the phase distribution of amorphous or partially crystalline organic materials at the nanoscale and analyzing the local atomic structure of individual phases has been a long-time challenge. We propose a new approach for imaging the phase distribution and for analyzing the local structure of organic materials based on scanning transmission electron diffraction (4D-STEM) pair distribution function analysis (PDF). We show that electron diffraction based PDF analysis can be used to characterize the short- and medium-range order in aperiodically packed organic molecules. Moreover, we show that 4D-STEM-PDF does not only provide local structural information with a resolution of a few nanometers, but can also be used to image the phase distribution of organic composites. The distinct and thickness independent contrast of the phase image is generated by utilizing the structural difference between the different types of molecules and taking advantage of the dose efficiency due to use of the full scattering signal. Therefore, this approach is particularly interesting for imaging unstained organic or polymer composites without distinct valence states for electron energy loss spectroscopy. We explore the possibilities of this new approach using [6,6]-phenyl-C61- butyric acid methyl ester (PC61BM) and poly(3-hexylthiophene-2,5-diyl) (P3HT) as the archetypical and best-investigated semiconductor blend used in organic solar cells, compare our phase distribution with virtual dark-field analysis and validate our approach by electron energy loss spectroscopy.
Treatment-induced brain tissue necrosis: a clinical challenge in neuro-oncology
Authors: Winter Sebastian F , Loebel Franziska , Loeffler Jay , Batchelor Tracy T , Martinez-Lage Maria , Vajkoczy Peter , Dietrich Jorg
Published: February 2019

Cancer therapy-induced adverse effects on the brain are a major challenge in neuro-oncology. Brain tissue necrosis (treatment necrosis [TN]) as a consequence of brain directed cancer therapy remains an insufficiently characterized condition with diagnostic and therapeutic difficulties and is frequently associated with significant patient morbidity.

A better understanding of the underlying mechanisms, improvement of diagnostic tools, development of preventive strategies, and implementation of evidence-based therapeutic practices are pivotal to improve patient management. In this comprehensive review, we address existing challenges associated with current TN-related clinical and research practices and highlight unanswered questions and areas in need of further research with the ultimate goal to improve management of patients affected by this important neuro-oncological condition.
A National Snapshot Detailing the Impact of Parkinson's Disease on the Cost and Outcome Profiles of Fusion Procedures for Cervical Myelopathy
Authors: Martini Michael L , Deutsch Brian C , Neifert Sean N , Caridi John M
Published: February 2019

BACKGROUND

Studies suggest a higher prevalence of cervical deformities in Parkinson's Disease (PD) patients who predispose to cervical myelopathy (CM). Despite the profound effect of CM on function and quality of life, no study has assessed the influence of PD on costs and outcomes of fusion procedures for CM.

OBJECTIVE

To conduct the first national-level study that provides a snapshot of the current outcome and cost profiles for different fusion procedures for CM in PD and non-PD populations.

METHODS

Patients with or without PD who underwent cervical decompression and fusion anteriorly (ACDF), posteriorly (PCDF), or both (Frontback), for CM were identified from the 2013 to 2014 National Inpatient Sample using International Classification of Disease codes.

RESULTS

A total of 75 870 CM patients were identified, with 535 patients (0.71%) also having PD. Although no difference existed between in-hospital mortality rates, overall complication rates were higher in PD patients (38.32% vs 22.05%; P < .001). PD patients had higher odds of pulmonary (P = .002), circulatory (P = .020), and hematological complications (P = .035). Following ACDFs, PD patients had higher odds of complications (P = .035), extended hospitalization (P = .026), greater total charges (P = .003), and nonhome discharge (P = .006). Although PCDFs and Frontbacks produced higher overall complication rates for both populations than ACDFs, PD status did not affect complication odds for these procedures.

CONCLUSION

PD may increase risk for certain adverse outcomes depending on procedure type. This study provides data with implications in healthcare delivery, policy, and research regarding a patient population that will grow as our population ages and justifies further investigation in future prospective studies.
Can planets exist in the habitable zone of 55 Cancri?
Authors: Satyal Suman , Cuntz Manfred
Published: February 2019

The aim of our study is to explore the possible existence of Earth-mass planets in the habitable zone of 55 Cancri, an effort pursued based on detailed orbital stability simulations. This star is known to possess (at least) five planets with masses ranging between super-Earth and Jupiter-type. Additionally, according to observational constraints, there is a space without planets between ∼0.8 au and ∼5.7 au, and it is noted that the inner part of this gap largely coincides with 55 Cnc’s habitable zone—a sincere motivation for the search of potentially habitable planets. It has previously been argued that terrestrial habitable planets are able to exist in the 55 Cnc system, including a planet at ∼1.5 au. We explore this possibility through employing sets of orbital integrations and assuming an integration time of 50 Myr. We found that the possibility of Earth-mass planets in the system’s habitable zone strongly depends on the adopted system parameters, notably the eccentricity of 55 Cnc-f, which is controversial as both a high value (e ∼ 0.32) and a low value (e ∼ 0.08) have previously been deduced. In the case where the low value, the more plausible and most recent value, is adopted (together with other updates for the system parameters), Earth-mass planets would be able to exist in the gap between 1.0 au and 2.0 au, thus implying the possibility of habitable system planets. Thus, 55 Cnc should be considered a favorable target for future habitable planet search missions.
Taxonomic synthesis of the eastern North American millipede genus Pseudopolydesmus (Diplopoda: Polydesmida: Polydesmidae), utilizing high-detail ultraviolet fluorescence imaging
Authors: Sierwald Petra , Hennen Derek A , Zahnle Xavier J , Ware Stephanie , Marek Paul E
Published: February 2019

The species of the eastern North American millipede genus Pseudopolydesmus are reviewed. Synonyms and comprehensive literature citations are provided for each of the eight recognized species. Diagnostic morphology of the genus, including clarification of male gonopod terminology, is reviewed and defined using scanning electron microscopy and high-quality macrophotographic images, including those in which ultraviolet fluorescence was induced to produce detailed images of morphological structures. Based on the examination of available type material, the following eight species are recognized: (1) Pseudopolydesmus erasus; (2) Pseudopolydesmus canadensis; (3) Pseudopolydesmus collinus; (4) Pseudopolydesmus pinetorum; (5) Pseudopolydesmus minor; (6) Pseudopolydesmus caddo; (7) Pseudopolydesmus paludicolus; and (8) Pseudopolydesmus serratus. The species names Polydesmus neoterus and Polydesmus euthetus are here placed as junior subjective synonyms of Ps. minor (both syn. nov.), and Polydesmus natchitoches is placed as a junior subjective synonym of Ps. pinetorum (syn. nov.).
How fast are cells dividing: Probabilistic model of continuous labeling assays
Authors: Rode Julian , Goerke Torsten , Brusch Lutz , Rost Fabian
Published: February 2019

Correct estimates of cell proliferation rates are crucial for quantitative models of the development, maintenance and regeneration of tissues. Continuous labeling assays are used to infer proliferation rates in vivo. So far, the experimental and theoretical study of continuous labeling assays focused on the dynamics of the mean labeling-fraction but neglected stochastic effects. To study the dynamics of the labeling-fraction in detail and fully exploit the information hidden in fluctuations, we developed a probabilistic model of continuous labeling assays which incorporates biological variability at different levels, between cells within a tissue sample but also between multiple tissue samples. Using stochastic simulations, we find systematic shifts of the mean-labeling fraction due to variability in cell cycle lengths. Using simulated data as ground truth, we show that current inference methods can give biased proliferation rate estimates with an error of up to 40 %. We derive the analytical solution for the Likelihood of our probabilistic model. We use this solution to infer unbiased proliferation rate estimates in a parameter recovery study. Furthermore, we show that the biological variability on different levels can be disentangled from the fluctuations in the labeling data. We implemented our model and the unbiased parameter estimation method as an open source Python tool and provide an easy to use web service for cell cycle length estimation from continuous labeling assays (https://imc.zih.tu-dresden.de/cellcycle).
Insect herbivory and avian insectivory in novel native oak forests: divergent effects of stand size and connectivity
Authors: Valdés-Correcher Elena , Halder Inge van , Barbaro Luc , Castagneyrol Bastien , Hampe Arndt
Published: February 2019

The value of novel native broadleaf woodlands for biodiversity conservation is important to consider for adequate forest management in rural landscapes. Passive reforestation has been proposed as a cost-efficient tool for creating networks of novel native forest stands that would help restoring biodiversity and associated ecosystem services. Yet to date the ecological functioning of such stands remains strongly understudied compared to forest remnants resulting from longer-term fragmentation. We assessed how the size and connectivity of newly established Pedunculate oak (Quercus robur L.) stands in rural landscapes of SW France affect rates of herbivory by different insect guilds as well as rates of avian insectivory and the abundance and richness of insectivorous birds. Comparing 18 novel forest stands along a gradient of size (0.04-1.15 ha) and cover of broadleaf forests in the surroundings (0-30% within a 500 radius), we found that even the smallest stands are colonised by leaf miners and chewers/skeletonizers, and that rates of herbivory are globally comparable to those reported from older and larger oak forests. The size of stands had a relatively minor effect on herbivory, whereas it increased the abundance of insectivorous bird. It also determined rates of avian insectivory as estimated by an experiment with plasticine caterpillars. These rates were however rather low and unrelated with the extent of herbivory in the stand. Overall, our study indicates that insect herbivores tend to react more rapidly to the establishment of novel native forests than their avian predators as the latter may depend on the development of larger patches of suitable habitat in the surrounding landscape. To favour a rapid build-up of diverse, and hence stable, trophic networks involving insect herbivores and their predators, woodland creation schemes should therefore primarily focus on habitat size and quality.
Pancreatic Stellate Cells Secrete Deoxycytidine Conferring Resistance to Gemcitabine in PDAC
Authors: Dalin Simona , Sullivan Mark R. , Kreidl Emanuel , Lau Allison N. , Grauman-Boss Beatrice , Fenoglio Silvia , Luengo Alba , Vander Heiden Matthew G. , Lauffenburger Douglas A. , Hemann Michael T.
Published: February 2019

Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer deaths in the United States. The deoxynucleoside analog gemcitabine is among the most effective therapies to treat PDAC; however, nearly all patients treated with gemcitabine either fail to respond or rapidly develop resistance. One hallmark of PDAC is a striking accumulation of stromal tissue surrounding the tumor, and this accumulation of stroma can contribute to therapy resistance. To better understand how stroma limits response to therapy, we investigated cell-extrinsic mechanisms of resistance to gemcitabine. We show that conditioned media from pancreatic stellate cells (PSC), as well as from other fibroblasts, protects PDAC cells from gemcitabine toxicity. We find that the PSC conditioned media protective effect is mediated by secretion of deoxycytidine, but not other deoxynucleosides, through equilibrative nucleoside transporters. Deoxycytidine inhibits the processing of gemcitabine in PDAC cells, thus reducing the effect of gemcitabine and other nucleoside analogs on cancer cells. Our results suggest that reducing deoxycytidine production in PSCs may increase the efficacy of nucleoside analog therapies.

Additional Information

Funding: This project was funded in part by the NIH (NCI U54-217377), the MIT Center for Precision Cancer Medicine, and by the Koch Institute Support (core) Grant P30-CA14051 from the National Cancer Institute. S.D. was supported by the David H. Koch Fellowship in Cancer Research. A.N.L was a Robert Black Fellow of the Damon Runyon Cancer Research Foundation, DRG-2241-15 and was supported by a NIH Pathway to Independence Award (K99/R00), 1K99CA234221. M.T.H and M.G.V.H. acknowledges funding from the MIT Center for Precision Cancer Medicine and the Ludwig Center at MIT. M.G.V.H also acknowledges funding from the Lustgarten Foundation, SU2C, the MIT Center for Precision Cancer Medicine, the NCI, and an HHMI Faculty Scholar award.

Competing interests: M.G.V.H. is a consultant and advisory board member for Agios Pharmaceuticals, Aeglea Biotherapeutics, and Auron Therapeutics.
Experience-dependent tuning of early olfactory processing in the adult brain
Authors: Jernigan Christopher M. , Halby Rachael , Gerkin Richard C. , Sinakevitch Irina , Locatelli Fernando , Smith Brian H.
Published: February 2019

Experience-dependent plasticity in the central nervous system allows an animal to adaptively change their responses to stimuli over different time scales. In this study we explored the different time frames and mechanisms over which olfactory experience-dependent plasticity works. We measured the impact of experience on early olfactory processing by comparing naturally foraging animals with a diverse olfactory experience to animals from the same cohort that experienced a chronic reduction in adult olfactory experience. We placed age-matched sets of full-sister honey bees, Apis mellifera, into two different olfactory conditions, in which animals were allowed to forage ad libitum. In one condition (T), we reduced the olfactory experience of foraging bees by placing them in a tent in which both sucrose and pollen resources were associated with a single odor. In the second condition (F), bees were allowed to forage freely and therefore receive a diversity of naturally occurring resource-associated olfactory experiences. We found that bees with a reduced olfactory experience had less developed antennal lobes when compared to experienced foragers, suggesting early-adult sensory experience influences the development of olfactory processing. We next measured the antennal lobe glomerular responses to odors using calcium imaging, and found that diverse olfactory experience of bees also enhances the inter-individual variation in the glomerular response profiles to odors. Last, we measured the impact of this treatment in an olfactory learning assay. We found that bees with a reduced olfactory experience had more difficulty picking an odor out of a mixture, which led them to generalize more (or respond similarly) to different mixture components than bees with richer olfactory experiences. Our study highlights the impact of individual experience at multiple levels (i.e., behavioral, physiological, developmental) on early olfactory processing.
Discordant gene responses to radiation in humans and mice: hematopoietically humanized mice may save the day for radiation biomarker identification
Authors: Ghandhi Shanaz A. , Smilenov Lubomir , Pujol-Canadell Monica , Amundson Sally A
Published: February 2019

The mouse (Mus musculus) is an extensively used model of human disease and responses to stresses such as ionizing radiation. As part of our work developing gene expression biomarkers of radiation exposure, dose, and injury, we have found many genes are either up-regulated (e.g. CDKN1A, MDM2, BBC3, and CCNG1) or down-regulated (e.g. TCF4 and MYC) in both species after irradiation. However, we have also found genes that are consistently up-regulated in humans and down-regulated in mice (e.g. DDB2, PCNA, GADD45A, SESN1, RRM2B, KCNN4, IFI30, and PTPRO). Here we test a hematopoietically humanized mouse as a potential in vivo model for biodosimetry studies, measuring the response of these 14 genes one day after radiation exposure, and comparing it with that of human blood irradiated ex vivo, and blood from whole body irradiated mice. We found that human blood cells in the hematopoietically humanized mouse in vivo environment recapitulated the gene expression pattern expected from human cells, not the pattern seen from in vivo irradiated normal mice. The results of this study support the use of hematopoietically humanized mice as an in vivo model for radiation gene expression studies relevant to humans.
Substrate Affinity and Specificity of theScSth1p Bromodomain Are Fine-Tuned for Versatile Histone Recognition
Authors: Blus Bartlomiej J. , Hashimoto Hideharu , Seo Hyuk-Soo , Krolak Aleksandra , Debler Erik W.
Published: February 2019

Bromodomains recognize a wide range of acetylated lysine residues in histones and other nuclear proteins. Substrate specificity is critical for their biological function and arises from unique acetyl-lysine binding sites formed by variable loop regions. Here, we analyzed substrate affinity and specificity of the yeastScSth1p bromodomain, an essential component of the “Remodels theStructure ofChromatin” complex, and found that the wild-type bromodomain preferentially recognizes H3K14ac and H4K20ac peptides. Mutagenesis studies—guided by our crystal structure determined at 2.7 Å resolution—revealed loop residues Ser1276 and Trp1338 as key determinants for such interactions. Strikingly, point mutations of each of these residues substantially increased peptide binding affinity and selectivity, respectively. Our data demonstrate that theScSth1p bromodomain is not optimized for binding to an individual acetylation mark, but fine-tuned for interactions with several such modifications, consistent with the versatile and multivalent nature of histone recognition by reader modules such as bromodomains.

Highlights

TheScSth1p bromodomain preferentially recognizes H3K14ac and H4K20ac peptides

Ser1276 and Trp1338 are key determinants of substrate affinity and specificity

Mutations of these residues drastically increase substrate affinity and specificity

TheScSth1p bromodomain is fine-tuned for promiscuous histone tail recognition

Graphical Abstract
Biochemical and structural characterization of a highly active branched-chain amino acid aminotransferase from Pseudomonas sp. for efficient biosynthesis of chiral amino acids
Authors: Zheng Xinxin , Cui Yinglu , Li Tao , Li Ruifeng , Guo Lu , Li Defeng , Wu Bian
Published: February 2019

Aminotransferases (ATs) are important biocatalysts for the synthesis of chiral amines because of their capability of introducing amino group into ketones or keto acids as well as their high enantioselectivity, high regioselectivity and no requirement of external addition of cofactor. Among all ATs, branched-chain amino acid aminotransferase (BCAT) can reversibly catalyse branched-chain amino acids (BCAAs), including L-valine, L-leucine, and L-isoleucine, with α-ketoglutaric acid to form the corresponding ketonic acids and L-glutamic acid. Alternatively, BCATs have been used for the biosynthesis of unnatural amino acids, such as L-tert-leucine. In the present study, the BCAT from Pseudomonas sp. (PsBCAT) was cloned and expressed in Escherichia coli for biochemical and structural analyses. The optimal reaction temperature and pH of PsBCAT were 40 °C and 8.5, respectively. PsBCAT exhibited a comparatively broader substrate spectrum, and showed remarkably high activity with L-leucine, L-valine, L-isoleucine and L-methionine with activities of 105 U/mg, 127 U/mg, 115 U/mg and 98 U/mg, respectively. Additionally, PsBCAT had activities with aromatic L-amino acids, L-histidine, L-lysine, and L-threonine. To analyse the catalytic mechanism of PsBCAT with the broad substrate spectrum, the crystal structure of PsBCAT was also determined. Finally, conjugated with the ornithine aminotransferase (OrnAT) from Bacillus subtilis, the coupled system was applied to the preparation of L-tert-leucine with 83% conversion, which provided an approximately 2.7-fold higher yield than the single BCAT reaction.

IMPORTANCE

Despite the enormous potential of BCATs, the vast majority of enzymes still lack suitably broad substrate scope and activity, thus new sources and novel enzymes are currently being investigated. Here, we described a previously uncharacterized PsBCAT, which showed a surprisingly wide substrate range and was more active towards BCAAs. This substrate promiscuity is unique for the BCAT family and could prove useful in industrial applications. Based on the determined crystal structure, we found some differences in the organization of the substrate binding cavity, which may influence the substrate specificity of the enzyme. Moreover, we demonstrated efficient biocatalytic asymmetric synthesis of L-tert-leucine using a coupling system, which can be used to remove the inhibitory by-product, and to shift the reaction equilibrium towards the product formation. In summary, the structural and functional characteristics of PsBCAT were analysed in detail, and this information will play an important role in the synthesis of chiral amino acids and will be conducive to industrial production of enantiopure chiral amines by aminotransferase.
Elevated risk of invasive group A streptococcal disease and host genetic variation in the human leukocyte antigen locus
Authors: Parks Tom , Elliott Katherine , Lamagni Theresa , Auckland Kathryn , Mentzer Alexander J. , Guy Rebecca , Cartledge Doreen , Strakova Lenka , O’Connor Daniel , Pollard Andrew J. , Neville Matthew J. , Mahajan Anubha , Ashrafian Houman , Chapman Stephen J. , Hill Adrian V. S. , Sriskandan Shiranee , Knight Julian C.
Published: February 2019

Invasive group A streptococcal (GAS) disease is uncommon but carries a high case-fatality rate relative to other infectious diseases. Given the ubiquity of mild GAS infections, it remains unclear why healthy individuals will occasionally develop life-threatening infections, raising the possibility of host genetic predisposition. Here, we present the results of a case-control study including 43 invasive GAS cases and 1,540 controls. Using HLA imputation and linear mixed-models, we find each copy of theHLA-DQA1*01:03 allele associates with a two-fold increased risk of disease (odds ratio 2.3, 95% confidence interval 1.3-4.4,P=0.009), an association which persists with classical HLA typing of a subset of cases and analysis with an alternative large control dataset with validated HLA data. Moreover, we propose the association is driven by the allele itself rather than the background haplotype. Overall this finding provides impetus for further investigation of the immunogenetic basis of this devastating bacterial disease.
EXOCYST70A3 controls root system depth in Arabidopsis via the dynamic modulation of auxin transport
Authors: Ogura Takehiko , Goeschl Christian , Filiault Daniele , Mirea Madalina , Slovak Radka , Wolhrab Bonnie , Satbhai Santosh B. , Busch Wolfgang
Published: February 2019

Root system architecture (RSA), the distribution of roots in soil, plays a major role in plant survival. RSA is shaped by multiple developmental processes that are largely governed by the phytohormone auxin, suggesting that auxin regulates responses of roots that are important for local adaptation. However, auxin has a central role in numerous processes and it is unclear which molecular mechanisms contribute to the variation in RSA for environmental adaptation. Using natural variation in Arabidopsis, we identify EXOCYST70A3 as a modulator of the auxin system that causes variation in RSA by acting on PIN4 protein distribution. Allelic variation and genetic perturbation of EXOCYST70A3 leads to alteration of root gravitropic responses, resulting in a different RSA depth profile and drought resistance. Overall our findings suggest that the local modulation of the pleiotropic auxin pathway can gives rise to distinct root system architectures that can be adaptive in specific environments.
Basal protrusions mediate spatiotemporal patterns of spinal neuron differentiation
Authors: Hadjivasiliou Zena , Moore Rachel , McIntosh Rebecca , Galea Gabriel , Clarke Jon , Alexandre Paula
Published: February 2019

During early spinal cord development, neurons of particular subtypes differentiate with a sparse periodic pattern while later neurons differentiate in the intervening space to eventually produce continuous columns of similar neurons. The mechanisms that regulate this spatiotemporal pattern are unknown.In vivoimaging of zebrafish reveals differentiating spinal neurons transiently extend two long protrusions along the basal surface of the spinal cord prior to axon initiation. These protrusions express Delta protein consistent with the possibility they influence Notch signalling at a distance of several cell diameters. Experimental reduction of laminin expression leads to smaller protrusions and shorter distances between differentiating neurons. The experimental data and a theoretical model support the proposal that the pattern of neuronal differentiation is regulated by transient basal protrusions that deliver temporally controlled lateral inhibition mediated at a distance. This work uncovers novel, stereotyped protrusive activity of new-born neurons that organizes long distance spatiotemporal patterning of differentiation.