bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immunological and physiological observations in baboons with life‐supporting genetically engineered pig kidney grafts
Authors: Iwase Hayato , Hara Hidetaka , Ezzelarab Mohamed , Li Tao , Zhang Zhongqiang , Gao Bingsi , Liu Hong , Long Cassandra , Wang Yi , Cassano Amy , Klein Edwin , Phelps Carol , Ayares David , Humar Abhinav , Wijkstrom Martin , Cooper David K. C. 
Published: March 2017

AbstractBackgroundGenetically engineered pigs could provide a source of kidneys for clinical transplantation. The two longest kidney graft survivals reported to date have been 136 and 310 days, but graft survival >30 days has been unusual until recently.MethodsDonor pigs (n=4) were on an α1,3‐galactosyltransferase gene‐knockout (GTKO)/human complement regulatory protein (CD46) background (GTKO/CD46). In addition, the pigs were transgenic for at least one human coagulation regulatory protein. Two baboons received a kidney from a six‐gene pig (GroupA) and two from a three‐gene pig (GroupB). Immunosuppressive therapy was identical in all four cases and consisted of anti‐thymoglobulin (ATG)+anti‐CD20mAb (induction) and anti‐CD40mAb+rapamycin+corticosteroids (maintenance). Anti‐TNF‐α and anti‐IL‐6R mAbs were administered to reduce the inflammatory response. Baboons were followed by clinical/laboratory monitoring of immune/coagulation/inflammatory/physiological parameters. At biopsy or euthanasia, the grafts were examined by microscopy.ResultsThe two GroupA baboons remained healthy with normal renal function >7 and >8 months, respectively, but then developed infectious complications. However, no features of a consumptive coagulopathy, eg, thrombocytopenia and reduction of fibrinogen, or of a protein‐losing nephropathy were observed. There was no evidence of an elicited anti‐pig antibody response, and histology of biopsies taken at approximately 4, 6, and 7 months and at necropsy showed no significant abnormalities. In contrast, both GroupB baboons developed features of a consumptive coagulopathy and required euthanasia on day 12.ConclusionsThe combination of (i) a graft from a specific six‐gene genetically modified pig, (ii) an effective immunosuppressive regimen, and (iii) anti‐inflammatory therapy prevented immune injury, a protein‐losing nephropathy, and coagulation dysfunction for >7 months. Although the number of experiments is very limited, our impression is that expression of human endothelial protein C receptor (±CD55) in the graft is important if coagulation dysregulation is to be avoided.
Examination of CRISPR/Cas9 design tools and the effect of target site accessibility on Cas9 activity
Authors: Lee Ciaran M. , Davis Timothy H. , Bao Gang 
Published: March 2017

New Findings
What is the topic of this review?
In this review, we analyse the performance of recently described tools for CRISPR/Cas9 guide RNA design, in particular, design tools that predict CRISPR/Cas9 activity.

What advances does it highlight?
Recently, many tools designed to predict CRISPR/Cas9 activity have been reported. However, the majority of these tools lack experimental validation. Our analyses indicate that these tools have poor predictive power. Our preliminary results suggest that target site accessibility should be considered in order to develop better guide RNA design tools with improved predictive power.

The recent adaptation of the clustered regulatory interspaced short palindromic repeats (CRISPR)/CRISPR‐associated protein 9 (Cas9) system for targeted genome engineering has led to its widespread application in many fields worldwide. In order to gain a better understanding of the design rules of CRISPR/Cas9 systems, several groups have carried out large library‐based screens leading to some insight into sequence preferences among highly active target sites. To facilitate CRISPR/Cas9 design, these studies have spawned a plethora of guide RNA (gRNA) design tools with algorithms based solely on direct or indirect sequence features. Here, we demonstrate that the predictive power of these tools is poor, suggesting that sequence features alone cannot accurately inform the cutting efficiency of a particular CRISPR/Cas9 gRNA design. Furthermore, we demonstrate that DNA target site accessibility influences the activity of CRISPR/Cas9. With further optimization, we hypothesize that it will be possible to increase the predictive power of gRNA design tools by including both sequence and target site accessibility metrics.
Functional impact of an oculopharyngeal muscular dystrophy mutation in PABPN1
Authors: García‐Castañeda Maricela , Vega Ana Victoria , Rodríguez Rocío , Montiel‐Jaen Maria Guadalupe , Cisneros Bulmaro , Zarain‐Herzberg Angel , Avila Guillermo 
Published: March 2017

Key points
Mutations in the gene encoding poly(A)‐binding protein nuclear 1 (PABPN1) result in oculopharyngeal muscular dystrophy (OPMD). This disease is of late‐onset, but the underlying mechanism is unclear.
Ca2+ stimulates muscle growth and contraction and, because OPMD courses with muscle atrophy and weakness, we hypothesized that the homeostasis of Ca2+ is altered in this disorder.
C2C12 myotubes were transfected with cDNAs encoding either PABPN1 or the PABPN1‐17A OPMD mutation. Subsequently, they were investigated concerning not only excitation–contraction coupling (ECC) and intracellular levels of Ca2+, but also differentiation stage and nuclear structure.
PABPN1‐17A gave rise to: inhibition of Ca2+ release during ECC, depletion of sarcoplasmic reticulum Ca2+ content, reduced expression of ryanodine receptors, altered nuclear morphology and incapability to stimulate myoblast fusion.
PABPN1‐17A failed to inhibit ECC in adult muscle fibres, suggesting that its effects are primarily related to muscle regeneration.
AbstractOculopharyngeal muscular dystrophy (OPMD) is linked to mutations in the gene encoding poly(A)‐binding protein nuclear 1 (PABPN1). OPMD mutations consist of an expansion of a tract that contains 10 alanines (to 12–17). This disease courses with muscle weakness that begins in adulthood, but the underlying mechanism is unclear. In the present study, we investigated the functional effects of PABPN1 and an OPMD mutation (PABPN1‐17A) using myotubes transfected with cDNAs encoding these proteins (GFP‐tagged). PABPN1 stimulated myoblast fusion (100%), whereas PABPN1‐17A failed to mimic this effect. Additionally, the OPMD mutation markedly altered nuclear morphology; specifically, it led to nuclei with a more convoluted and ovoid shape. Although PABPN1 and PABPN1‐17A modified the expression of sarcoplasmic/endoplasmic reticulum Ca2+‐ATPase and calsequestrin, the corresponding changes did not have a clear impact on [Ca2+]. Interestingly, neither L‐type Ca2+ channels, nor voltage‐gated sarcoplasmic reticulum (SR) Ca2+ release (VGCR) was altered by PABPN1. However, PABPN1‐17A produced a selective inhibition of VGCR (50%). This effect probably arises from both lower expression of RyR1 and depletion of SR Ca2+. The latter, however, was not related to inhibition of store‐operated Ca2+ entry. Both PABPN1 constructs promoted a moderated decrease in cytosolic [Ca2+], which apparently results from down‐regulation of excitation‐coupled Ca2+ entry. On the other hand, PABPN1‐17A did not alter ECC in muscle fibres, suggesting that adult muscle is less prone to developing deleterious effects. These results demonstrate that PABPN1 proteins regulate essential processes during myotube formation and support the notion that OPMD involves disruption of myogenesis, nuclear structure and homeostasis of Ca2+.
La activación de un patrimonio nacional en Norpatagonia, Argentina
Authors: Bersten Lara 
Published: March 2017

En este artículo se analizan aspectos relativos a la creación de las áreas protegidas en Argentina, en ligazón con el proceso de construcción del Estado y de consolidación de la Nación en Norpatagonia. Recuperamos la figura de Francisco Moreno y de Exequiel Bustillo, dos personajes clave en la creación de las mismas y en la impronta simbólica y estética otorgada a la Patagonia argentina. Se sostiene que a partir de sus trayectorias, vinculaciones políticas y propuestas se sentaron las bases del ideario fundacional de los Parques Nacionales, las cuales destacaban el rol de la naturaleza como inspiradora de los valores de la patria. Asimismo, se utiliza la categoría de analítica de “activación patrimonial” con el objeto de ahondar en el interrogante acerca de por qué ciertos espacios naturales son valorados como patrimonio del conjunto de la nación y por ende deben ser preservados. Los resultados que aquí se presentan provienen del trabajo con fuentes documentales y de entrevistas en profundidad, en el marco de una investigación en el Departamento Los Lagos, provincia de Neuquén, Argentina, territorio que integra el Parque Nacional Nahuel Huapi.
Hacia un estado del arte de la historia urbana en Colombia: el caso de Bogotá
Authors: Rueda Cáceres Liliana , Plata Quezada William Elvis 
Published: March 2017

Este artículo es resultado de una investigación en historia urbana que indagó específicamente sobre un hecho puntual ocurrido en la Bogotá de 1939, la demolición del antiguo convento de Santo Domingo. Trabajo que abrió una puerta inmensa, la historia urbana de Bogotá, sobre la que hacemos una primera aproximación en la que se examina dentro de los marcos conceptuales propuestos para la historia urbana, la estrecha relación existente entre historia de la arquitectura e historia urbana y se observan y destacan ejercicios de análisis que funden de manera indisoluble el problema de la forma y la arquitectura de la ciudad con las condiciones y tramas sociales que subyacen tras esta.
Transthoracic ultrasonography for the follow-up of a chronic lymphocytic leukemia patient with chemotherapy-induced immunosuppression prior to allogeneic stem cell transplantation. A case report
Authors: Frinc Ioana , Dima Delia , Chitic Mariana , Berce Cristian , Berindan-Neagoe Ioana , Tat Tiberiu , Tanase Alina , Tomuleasa Ciprian , Bojan Anca 
Published: March 2017

In the last years, significant progress has been made in the clinical follow-up of leukemia patients who are especially prone to various infections because of the specific immunosuppressive state following chemotherapy. The follow-up of such patients is of special interest and is based on modern imaging protocols especially computer tomography (CT). Still, CT may not always be effective in the diagnosing of respiratory infections. We report a chronic lymphocytic leukemia patient in which the pleuro-pulmonary complications were successfully diagnosed and followed up using transthoracic ultrasonography.
Twelve-Week Exercise Influences Memory Complaint but not Memory Performance in Older Adults: A Randomized Controlled Study
Authors: Iuliano Enzo , Fiorilli Giovanni , Aquino Giovanna , Di Costanzo Alfonso , Calcagno Giuseppe , di Cagno Alessandra 
Published: March 2017

This study aimed to evaluate the effects of different types of exercise on memory performance and memory complaint after a 12-week intervention. Eighty community-dwelling volunteers, aged 66.96 ± 11.73 years, were randomly divided into four groups: resistance, cardiovascular, postural, and control groups (20 participants for each group). All participants were tested for their cognitive functions before and after their respective 12-week intervention using Rey memory words test, Prose memory test, and Memory Complaint Questionnaire (MAC-Q). Statistical analysis showed that the three experimental groups significantly improved MAC-Q scores in comparison with the control group (p < .05). The variation of MAC-Q scores and the variations of Rey and Prose memory tests scores were not correlated. These results indicate that the 12-week interventions exclusively influenced memory complaint but not memory performance. Further investigations are needed to understand the relation between memory complaint and memory performance, and the factors that can influence this relationship.
Draft Genome Sequence of
Pseudomonas
sp. BDAL1 Reconstructed from a Bakken Shale Hydraulic Fracturing-Produced Water Storage Tank Metagenome
Authors: Lipus Daniel , Ross Daniel , Bibby Kyle , Gulliver Djuna 
Published: March 2017

ABSTRACT

We report the 5,425,832 bp draft genome of
Pseudomonas
sp. strain BDAL1, recovered from a Bakken shale hydraulic fracturing-produced water tank metagenome. Genome annotation revealed several key biofilm formation genes and osmotic stress response mechanisms necessary for survival in hydraulic fracturing-produced water.
Genome Sequence of Cauliflower Mosaic Virus Identified in Earwigs (
Doru luteipes
) through a Metagenomic Approach
Authors: Godinho Márcio Tadeu , Paula Débora Pires , Varsani Arvind , Ribeiro Simone Graça 
Published: March 2017

ABSTRACT

Here we report the first complete genome sequence of a cauliflower mosaic virus from Brazil, obtained from the gut content of the predator earwig (
Doru luteipes
). This virus has a genome of 8,030 nucleotides (nt) and shares 97% genome-wide identity with an isolate from Argentina.
Draft Genome Sequence of Francisella noatunensis subsp.
orientalis
STIR-GUS-F2f7, a Highly Virulent Strain Recovered from Diseased Red Nile Tilapia Farmed in Europe
Authors: Ramírez-Paredes José Gustavo , Larsson Pär , Wehner Stefanie , Bekaert Michaël , Öhrman Caroline , Metselaar Matthijs , Thompson Kimberly Dawn , Richards Randolph Harvey , Penman David James , Adams Alexandra 
Published: March 2017

ABSTRACT

A highly virulent strain of
Francisella noatunensis
subsp.
orientalis
, STIR-GUS-F2f7, was isolated from moribund red Nile tilapia (
Oreochromis niloticus
) farmed in Europe. In this communication, the complete genome sequencing of this bacterium is reported.
Genome Sequences of Four Nonhuman/Nonclinical Salmonella enterica Serovar Kentucky ST198 Isolates Recovered between 1972 and 1973
Authors: Kim Seon-Woo , Haley Bradd J. , Roberson Dwayne , Allard Marc , Hammack Thomas S. , Brown Eric W. , Van Kessel Jo Ann S. 
Published: March 2017

ABSTRACT

Salmonella enterica
serovar Kentucky is a polyphyletic member of
S. enterica
subclade A1 with multiple sequence types that often colonize the same hosts but in different frequencies on different continents. To evaluate the genomic features involved in
S
. Kentucky host specificity, we sequenced the genomes of four isolates recovered in the 1970s.
Draft Genome Sequences of 11 Lactococcus lactis subsp.
cremoris
Strains
Authors: Wels Michiel , Backus Lennart , Boekhorst Jos , Dijkstra Annereinou , Beerthuyzen Marke , Siezen Roland J. , Bachmann Herwig , van Hijum Sacha A. F. T. 
Published: March 2017

ABSTRACT

The lactic acid bacterium
Lactococcus lactis
is widely used for the fermentation of dairy products. Here, we present the draft genome sequences of 11
L. lactis
subsp.
cremoris
strains isolated from different environments.
Gradual escalation of use-of-force reduces police officer injury
Authors: Jetelina Katelyn K , Reingle Gonzalez Jennifer M , Bishopp Stephen A 
Published: March 2017

ObjectiveTo examine how escalation through the force continuum predicts officer injury in the presence of citizen aggression, while controlling for extraneous factors, like citizen and officer characteristics.MethodsCross-sectional data were extracted from 2244 use-of-force reports from the Dallas Police Department in 2015. Multilevel, mixed logistic regression models were used to evaluate the relationship between use of force and officer injury. Multilevel path analysis tested indirect and direct relationships between citizen aggression and officer injury.ResultsResults suggest that gradual escalation through the force continuum significantly decreases officer injury when a citizen is actively aggressive (β=−1.06, p value <0.001). Further, non-Hispanic black officers (β=−0.22, p value <0.001) and Hispanic officers (β=−0.08, p value <0.05) are less likely to gradually escalate through the force continuum, due to lower odds of verbal commands (black: OR=0.51, 95% CI 0.39 to 0.68; Hispanic: OR=0.77, 95% CI 0.60 to 0.99) and hard-empty hand control (black: OR=0.58, 95% CI 0.43 to 0.77) compared with white officers. Finally, officers with higher tenure (β=−0.01, p value <0.001) are less likely to gradually escalate through the force continuum.ConclusionsEscalation through the force continuum significantly reduces police officer injury. Future research should assess whether further environmental or situational factors contribute to the strong relationship between use of force and officer injury. Also, reliability and validity testing of use-of-force reports is an imperative direction for future research.
The heterogeneous impact of a successful tobacco control campaign: a case study of Mauritius
Authors: Ross Hana , Moussa Leelmanee , Harris Tom , Ajodhea Rajive 
Published: March 2017

BackgroundMauritius has one of the highest smoking prevalences in Africa, contributing to its high burden of non-communicable diseases. Mauritius implemented a series of tobacco control measures from 2009 to 2012, including tobacco tax increases. There is evidence that these policies reduced tobacco consumption, but it is not clear what impact they had across different socioeconomic groups.MethodThe impact of tobacco control measures on different income groups was analysed by contrasting household tobacco expenditures reported in 2006–2007 and 2012 household expenditure surveys. We employed the seemingly unrelated regression model to assess the impact of tobacco use on other household expenditures and calculated Gini coefficients to assess tobacco expenditure inequality.ResultsFrom 2006 to 2012, excise taxes and retail cigarette prices increased by 40.6% and 15.3% in real terms, respectively. These increases were accompanied by numerous non-price tobacco control measures. The share of tobacco-consuming households declined from 35.7% to 29.3%, with the largest relative drop among low-income households. The Gini coefficient of household tobacco expenditures increased by 10.4% due to decreased spending by low-income households. Low-income households demonstrated the largest fall in their tobacco budget shares, and the impact of tobacco consumption on poverty decreased by 26.2%. Households that continued purchasing tobacco reduced their expenditures on transportation, communication, health, and education.ConclusionsThese results suggest that tobacco control policies, including sizeable tax increases, were progressive in their impact. We conclude that tobacco use increases poverty and inequality, but stronger tobacco control policies can mitigate the impact of tobacco use on impoverishment.
Global monopole in a broken-symmetric theory of gravitation
Authors: Tripathi Buddhi Vallabh , Nandan Hemwati , Purohit K. D. 
Published: March 2017

We investigate global monopole solutions in a particular kind of scalar–tensor theory of gravity, viz. the broken-symmetric theory of gravity. Invoking the “hedgehog” ansatz for the scalar field, we derive the metric corresponding to global monopole solutions. The global monopole solutions found are independent of the scale of symmetry breaking unlike the Barriola–Vilenkin global monopoles in Einstein’s General Relativity (GR) which intrinsically depend on the symmetry breaking scale.
Disrupting Androgen Receptor Signaling Induces Snail-Mediated Epithelial–Mesenchymal Plasticity in Prostate Cancer
Authors: Miao Lu , Yang Lin , Li Rui , Rodrigues Daniel N. , Crespo Mateus , Hsieh Jer-Tsong , Tilley Wayne D. , de Bono Johann , Selth Luke A. , Raj Ganesh V. 
Published: March 2017

Abstract
Epithelial-to-mesenchymal plasticity (EMP) has been linked to metastasis, stemness, and drug resistance. In prostate cancer, EMP has been associated with both suppression and activation of the androgen receptor (AR) signaling. Here we investigated the effect of the potent AR antagonist enzalutamide on EMP in multiple preclinical models of prostate cancer and patient tissues. Enzalutamide treatment significantly enhanced the expression of EMP drivers (ZEB1, ZEB2, Snail, Twist, and FOXC2) and mesenchymal markers (N-cadherin, fibronectin, and vimentin) in prostate cancer cells, enhanced prostate cancer cell migration, and induced prostate cancer transformation to a spindle, fibroblast-like morphology. Enzalutamide-induced EMP required concomitant suppression of AR signaling and activation of the EMP-promoting transcription factor Snail, as evidenced by both knockdown and overexpression studies. Supporting these findings, AR signaling and Snail expression were inversely correlated in C4-2 xenografts, patient-derived castration-resistant metastases, and clinical samples. For the first time, we elucidate a mechanism explaining the inverse relationship between AR and Snail. Specifically, we found that AR directly repressed SNAI1 gene expression by binding to specific AR-responsive elements within the SNAI1 promoter. Collectively, our findings demonstrate that de-repression of Snail and induction of EMP is an adaptive response to enzalutamide with implications for therapy resistance. Cancer Res; 77(11); 3101–12. ©2017 AACR.
Total Exchange Flow, Entrainment, and Diffusive Salt Flux in Estuaries
Authors: Wang Tao , Geyer W. Rockwell , MacCready Parker 
Published: March 2017

AbstractThe linkage among total exchange flow, entrainment, and diffusive salt flux in estuaries is derived analytically using salinity coordinates, revealing the simple but important relationship between total exchange flow and mixing. Mixing is defined and quantified in this paper as the dissipation of salinity variance. The method uses the conservation of volume and salt to quantify and distinguish the diahaline transport of volume (i.e., entrainment) and diahaline diffusive salt flux. A numerical model of the Hudson estuary is used as an example of the application of the method in a realistic estuary with a persistent but temporally variable exchange flow. A notable finding of this analysis is that the total exchange flow and diahaline salt flux are out of phase with respect to the spring–neap cycle. Total exchange flow reaches its maximum near minimum neap tide, but diahaline salt transport reaches its maximum during the maximum spring tide. This phase shift explains the strong temporal variation of stratification and estuarine salt content through the spring–neap cycle. In addition to quantifying temporal variation, the method reveals the spatial variation of total exchange flow, entrainment, and diffusive salt flux through the estuary. For instance, the analysis of the Hudson estuary indicates that diffusive salt flux is intensified in the wider cross sections. The method also provides a simple means of quantifying numerical mixing in ocean models because it provides an estimate of the total dissipation of salinity variance, which is the sum of mixing due to the turbulence closure and numerical mixing.
The Intricacies of User Adjustments of Alerting Thresholds
Authors: Meyer Joachim , Sheridan Thomas B. 
Published: March 2017

Objective: We address the question of necessary conditions for users to adjust system settings, such as alarm thresholds, correctly. Background: When designing systems, we need to decide which system functions users should control. Giving control to users empowers them, but users must have the relevant information and the ability to adjust settings correctly for their control to be beneficial. Method: Using the example of adjusting an alerting threshold, we analyze the conditions for when users can and when they cannot possibly adjust threshold settings adequately. Results: We identify two obstacles that limit users’ ability to adjust thresholds adequately: (a) the difficulty of determining the correct threshold settings, especially because of users’ strong response to false positive indications, and (b) the difficulty of collecting the information necessary for setting the threshold. Conclusion: Users often cannot identify the optimal settings for a system, so it is unlikely that they choose adequate system settings. Application: System designers must consider the difficulties users face and analyze them explicitly when deciding on user involvement in processes.