bluuebunny/crossref_metadata_2025 huggingface dataset:
Cholangiohepatitis in Dairy Cattle: 13 Cases
Authors: Gomez D.E. , Doré E. , Francoz D. , Desrochers A. , Pierre H. , Fecteau G.
Published: March 2017

Background

The signalment, clinicopathologic, bacteriological, histopathological, ultrasonographic characteristics, and the treatment and outcomes of adult cattle with cholangiohepatitis are poorly defined.

Animals

Thirteen Holstein cows with cholangiohepatitis.

Methods

Retrospective study of medical records of cattle admitted to theCHUVand theAVCbetween 1992 and 2012 and 2000 and 2012, respectively, for cattle older than 3 months of age with a histopathological diagnosis of cholangiohepatitis. Cholangiohepatitis was defined as the presence of portal inflammation surrounding or infiltrating bile ducts, with or without epithelial damage, and extending into the adjacent lobules.

Results

At the time of diagnosis of cholangiohepatitis, cows had decreased appetite (n = 7) or were anorectic (n = 6), had fever (n = 5), and had tachycardia (n = 8). Icterus was detected in 5 cows. Yellow discoloration was identified on the skin of the udder (n = 3), conjunctiva (n = 2), and vulva (n = 1). There was leukocytosis (n = 6), neutrophilia (n = 9), and hyperfibrinogenemia (n = 8). Alteration in the serum biochemistry profile included hyperglobulinemia (n = 8), hypoalbuminemia (n = 10), increased activity ofGGT(n = 12),AST(n = 8), andALP(n = 10), and hyperbilirubinemia (n = 10). Histopathological diagnosis included mild, subacute, nonsuppurative cholangiohepatitis (n = 4), mild suppurative cholangiohepatitis (n = 4), mild mixed (neutrophilic and lymphocytic) cholangiohepatitis (n = 3), and moderate, chronic, nonsuppurative cholangiohepatitis (n = 1). Six cows were discharged from the hospital, and 7 were euthanized.

Conclusions and Clinical Importance

Cholangiohepatitis is a rare condition in adult cattle. Antemortem diagnosis can be challenging because clinical signs are unspecific.
Quantitative Dietary Taurine Requirement for California Yellowtail, Seriola lalandi
Authors: Salze Guillaume P. , Stuart Kevin R. , Jirsa Dave O. , Davis D. Allen , Drawbridge Mark A.
Published: March 2017

Although taurine has been identified as a required nutrient in several Seriola species, there are no available quantitative data on dietary taurine requirements for these commercially important species and recommendations are highly variable. Therefore, juvenile Seriola lalandi were fed one of eight practical diets supplemented with graded levels of taurine (0.11–1.08% of the dry diet, analyzed) to estimate their taurine requirement. Response in growth rate, feed efficiency, and nutrient deposition were evaluated using a broken‐quadratic model and 4‐ and 5‐parameter saturation kinetic models (4‐SKM and 5‐SKM) Blood serum composition was analyzed using linear models. Requirement estimates based on growth rates (thermal‐unit growth coefficient) and protein deposition were similar at 0.26% (95% confidence interval [CI]: 0.23–0.28) and 0.29% (95% CI: 0.25–0.34) dietary taurine, respectively. Feed and protein deposition efficiencies were optimized at 0.26–1.02% and 0.26–1.00% dietary taurine, respectively. Taurine deposition in the animal was maximized at higher dietary levels (0.64%). Levels of serum taurine increased in response to dietary levels and peaked at around 0.80% dietary taurine. Concomitantly, serum urea and total amino acid levels decreased with increasing dietary taurine levels, suggesting a reduced amino acid catabolism relative to the aforementioned improvement in protein deposition efficiency.
Landscape features impact connectivity between soil populations: a comparative study of gene flow in earthworms
Authors: Dupont L. , Torres‐Leguizamon M. , René‐Corail P. , Mathieu J.
Published: March 2017

Landscape features are known to alter the spatial genetic variation of aboveground organisms. Here, we tested the hypothesis that the genetic structure of belowground organisms also responds to landscape structure. Microsatellite markers were used to carry out a landscape genetic study of two endogeic earthworm species, Allolobophora chlorotica (N = 440, eight microsatellites) and Aporrectodea icterica (N = 519, seven microsatellites), in an agricultural landscape in the North of France, where landscape features were characterized with high accuracy. We found that habitat fragmentation impacted genetic variation of earthworm populations at the local scale. A significant relationship was observed between genetic diversity (He, Ar) and several landscape features in A. icterica populations and A. chlorotica. Moreover, a strong genetic differentiation between sites was observed in both species, with a low degree of genetic admixture and high Fst values. The landscape connectivity analysis at the regional scale, including isolation by distance, least‐cost path and cost‐weighted distance approaches, showed that genetic distances were linked to landscape connectivity in A. chlorotica. This indicates that the fragmentation of natural habitats has shaped their dispersal patterns and local effective population sizes. Landscape connectivity analysis confirmed that a priori favourable habitats such as grasslands may constitute dispersal corridors for these species.
T cell lymphoblastic lymphoma/leukemia within an adrenocorticotropic hormone and thyroid stimulating hormone positive pituitary adenoma: A cytohistological correlation emphasizing importance of intra‐operative squash smear
Authors: Gupta Rakesh K. , Saran Ravindra K. , Srivastava Arvind K. , Jagetia Anita , Garg Lalit , Sharma Mehar C.
Published: March 2017

We present a rare case of primary pituitary T cell lymphoma/leukemia (T‐LBL) in association with adrenocorticotropic hormone (ACTH) and thyroid stimulating hormone (TSH) expressing pituitary adenoma in a 55‐year‐old woman highlighting the importance of intra‐operative squash smears examination. The patient presented with complaints of headache, diminution of vision and recent onset altered sensorium. MRI revealed a mass lesion in the sellar‐suprasellar region with non‐visualization of pituitary gland separately, extending to involve adjacent structures diagnosed as invasive pituitary macroadenoma. Intra‐operative tissue was sent for squash smear examination. The cytology showed a tumor comprising of sheets of immature lymphoid cells intermixed with clusters of pituitary acinar cells with many mitoses and tingible body macrophages. A diagnosis of presence of immature lymphoid cells within the pituitary was offered and differentials of infiltration by lymphoma cells from systemic disease versus primary central nervous lymphoma‐like lymphoma arising in the pituitary adenoma were considered. Later paraffin section examination and immunohistochemistry corroborated with the squash findings and a final diagnosis of primary pituitary T cell lymphoma/leukemia in association with ACTH and TSH expressing pituitary adenoma was made. To date, only six cases of primary pituitary T cell lymphomas, including three T‐LBL cases, have been reported. This is the seventh case and first one additionally describing cytohistological correlation and importance of intra‐operative cytology.
Didymodon imbricatus sp. nov. (Pottiaceae, Musci) from Heilongjiang, China
Authors: Kou Jin , Feng Chao
Published: March 2017

A new species, Didymodon imbricatus C. Feng & J. Kou, is described and illustrated from Nianzishan District, Heilongjiang Province, China. It is characterized mainly by short‐lanceolate to ovate‐lanceolate leaves with broadly acute to obtuse and strongly cucullate apex, leaf margins recurved throughout and bistratose in distal part, lamina red with KOH, costa ending below apex and usually spurred above midleaf, with guide cells in 2 layers below midleaf and without ventral stereids, and the presence of gemmae in the leaf axils. The new species is contrasted with similar species in the genus.
What's new in Rome IV?
Authors: Tack J. , Drossman D. A.
Published: March 2017

The functional gastrointestinal disorders (FGIDs) are the most common disorders seen in Gastroenterology clinical practice. The Rome process has generated consensus definitions of FGIDS, allowing to subdivide patients into diagnostic categories based on the symptom pattern. The Rome IV consensus, presented in 2016, is the most recent update of this diagnostic scheme. This article summarizes the main changes, which include the use of epidemiology‐based symptom thresholds to define FGIDs, characterization of FGIDS as disorders of Gut‐Brain interaction, and updates of criteria for esophageal disorders, irritable bowel syndrome and Biliary and Sphincter of Oddi disorders based on scientific and technical progress made over the last decade. The Rome IV consensus provides a standard for clinical and research approach to FGIDS for the coming years.
Resolution of deep eudicot phylogeny and their temporal diversification using nuclear genes from transcriptomic and genomic datasets
Authors: Zeng Liping , Zhang Ning , Zhang Qiang , Endress Peter K. , Huang Jie , Ma Hong
Published: March 2017

Explosive diversification is widespread in eukaryotes, making it difficult to resolve phylogenetic relationships. Eudicots contain c. 75% of extant flowering plants, are important for human livelihood and terrestrial ecosystems, and have probably experienced explosive diversifications. The eudicot phylogenetic relationships, especially among those of the Pentapetalae, remain unresolved.

Here, we present a highly supported eudicot phylogeny and diversification rate shifts using 31 newly generated transcriptomes and 88 other datasets covering 70% of eudicot orders.

A highly supported eudicot phylogeny divided Pentapetalae into two groups: one with rosids, Saxifragales, Vitales and Santalales; the other containing asterids, Caryophyllales and Dilleniaceae, with uncertainty for Berberidopsidales. Molecular clock analysis estimated that crown eudicots originated c. 146 Ma, considerably earlier than earliest tricolpate pollen fossils and most other molecular clock estimates, and Pentapetalae sequentially diverged into eight major lineages within c. 15 Myr. Two identified increases of diversification rate are located in the stems leading to Pentapetalae and asterids, and lagged behind the gamma hexaploidization.

The nuclear genes from newly generated transcriptomes revealed a well‐resolved eudicot phylogeny, sequential separation of major core eudicot lineages and temporal mode of diversifications, providing new insights into the evolutionary trend of morphologies and contributions to the diversification of eudicots.
Memory impairment and the mediating role of task difficulty in patients with schizophrenia
Authors: Grimes Kyrsten M. , Zanjani Anosha , Zakzanis Konstantine K.
Published: March 2017

Using meta‐analytic methods, we sought to synthesize the research literature on memory impairment in schizophrenia. Additionally, we compared performances across memory measures to determine if task difficulty (e.g., effortful encoding and retrieval vs non‐effortful encoding and retrieval) could account for variance across studies. Our primary measures of interest included the California Verbal Learning Test, Wechsler Memory Scale, Rey Auditory Verbal Learning Test, Hopkins Verbal Learning Test, Rey–Osterrieth Complex Figure Test, and the Benton Visual Retention Test. We searched for all studies that met inclusion criteria using PubMed, PsycINFO, Scholars Portal Search, and Google Scholar. Studies were included if: (i) they were published after 1980; (ii) healthy controls were compared to patients with schizophrenia; (iii) at least one of the noted measures of interest was employed in the primary study; and (iv) the primary study included data that could be transformed to point estimate effect sizes (i.e., Cohen's d). Cohen's d was calculated between patients and healthy controls, along with overall 95% confidence intervals. A two‐tailed independent samples t‐test was conducted to assess if performance differed on various paired subtests of the same domain. Large effect sizes were found for all memory tests. No significant differences were found between subtests. In conclusion, patients with schizophrenia experience significant verbal and visual memory impairments, which are not explained by task difficulty. Patients were unable to learn or retrieve more reliably despite repetition and cuing strategies, suggesting that memory impairment in the illness is not a function of task difficulty.
Portosystemic shunt as a bridge to liver transplantation in infants: A comparison of two techniques
Authors: Yoeli Dor , Galván N. Thao N. , Ashton Daniel J. , Kumm Kayla R. , Kueht Michael L. , Witte Ellen D. , Miloh Tamir A. , Cotton Ronald T. , Rana Abbas , O'Mahony Christine A. , Goss John A.
Published: March 2017

Portosystemic shunts can serve as a bridge to liver transplantation in patients with end‐stage liver disease by providing portal decompression to treat life‐threatening variceal bleeding and prevent recurrent episodes until an organ becomes available. The conventional TIPS procedure, however, is technically challenging to perform in infants due to the small size of their intrahepatic vasculature. We report two cases of emergent creation of portosystemic shunts as a bridge to liver transplantation in infants with life‐threatening variceal bleeding using a conventional TIPS technique in the first case and a percutaneous DIPS technique in the other. Both procedures were successful at reducing the portosystemic pressure gradient and preventing further variceal bleeds until a liver transplant could be performed. The novel percutaneous DIPS procedure is a valuable alternative to the conventional TIPS in infants, as it is better suited for small or challenging intrahepatic vascular anatomy.
Relationship Between Hydrothermal Alteration Index and Geological Attributes at Chuquicamata Cu–Mo Porphyry Deposit, Chile
Authors: Véliz Héctor , Campos Eduardo , Menzies Andrew , Valdivia Ljubitza
Published: March 2017

The distribution of mineral zones, hydrothermal alteration assemblages and ore associations are important geological attributes of the Chuquicamata Porphyry Cu–Mo deposit. The development and morphology of these attributes were influenced by syn‐mineralization structures with later modification of post‐mineralization tectonism to yield the present day form. In this work we evaluate the elemental mass transfer index due to hydrothermalism by using Pearce Element Ratios, using a database of 1110 samples consisting of elemental concentrations by chemical analysis. We study the relationship of the aforementioned index with the geological attributes in the porphyry as well as evaluate the type of information that the index provides according to its distribution, magnitude and variability. The magnitudes of the alteration index are organized into deciles, each of which represents a source of information, or macrostate. Within these, the geological attribute, or microstate, has a probability to participate that depends on the possible categorization of a particular attributes. The amount of information or uncertainty that each geological attribute provides to each decile of the distribution of the alteration index is determined by measuring the value of entropy. The results indicate that this distribution is controlled by the geometric–kinematic properties of syn‐mineralization structures that generate the primary pattern related to potassic alteration that develops in the hanging wall of the East Shear Zone. Subsequently the shape of the potassic alteration is modified by the kinematic effect imposed by the Americana and Estanques Blancos faults, and this broadly defines the geometry of the Qz–Mo event and the shape of the phyllic alteration. In addition, the sinistral‐inverse shear of the West Fault Zone allows the construction of an enriched blanket and also generates the drag fold that is characteristically observed in the south wall of the mine. All of the above events combine to yield the final geometry of the geological attributes that controls the shape and magnitude of the alteration index in the porphyry. The magnitude of the alteration index is mainly driven by the potassic and phyllic alteration stages. Potassic alteration is dominant in the first four deciles, while phyllic alteration is dominant in the last six deciles. Supergene mineralization attributes contribute discreetly to the average magnitude of the alteration index for each decile. The distribution of the probability of participation of the geological attributes in the distribution of the alteration index suggests that in the potassic alteration, biotite and green‐gray sericite facies contribute to strengthen the index in an associated manner, while in the phyllic alteration, the Qz–Ser textural type is the most significant.
Expert Views on Biological Threat Characterization for the U.S. Government: A Delphi Study
Authors: Watson Crystal R. , Watson Matthew C. , Ackerman Gary , Gronvall Gigi Kwik
Published: March 2017

Biological threat characterization (BTC) involves laboratory research conducted for the purpose of biological defense. BTC research is important for improving biological risk assessment and informing resource prioritization. However, there are also risks involved in BTC work, including potential for escape from the laboratory or the misuse of research results. Using a modified Delphi study to gather opinions from U.S. experts in biosecurity and biodefense, this analysis explores what principles and safeguards can maximize the benefits of BTC research and ensure that it is conducted safely and securely. Delphi participants were asked to give their opinions about the need for BTC research by the U.S. government (USG); risks of conducting this research; rules or guidelines that should be in place to ensure that the work is safe and accurate; components of an effective review and prioritization process; rules for when characterization of a pathogen can be discontinued; and recommendations about who in the USG should be responsible for BTC prioritization decisions. The findings from this research reinforce the need for BTC research at the federal level as well as a need for continued review and oversight of this research to maximize its effectiveness and reduce the risks involved. It also demonstrates the need for further discussion of what would constitute a “red line” for biothreat characterization research—research that should not be performed for safety, ethical, or practical reasons—and guidelines for when there is sufficient research in a given topic area so that the research can be considered completed.
Bayesian Model Selection for the Glacial–Interglacial Cycle
Authors: Carson Jake , Crucifix Michel , Preston Simon , Wilkinson Richard D.
Published: March 2017

A prevailing viewpoint in paleoclimate science is that a single paleoclimate record contains insufficient information to discriminate between typical competing explanatory models. Here we show that, by using the algorithm SMC2 (‘sequential Monte Carlo squared’) combined with novel Brownian-bridge-type proposals for the state trajectories, it is possible to estimate Bayes factors to sufficient accuracy to be able to select between competing models, even with relatively short time series. The results show that Monte Carlo methodology and computer power have now advanced to the point where a full Bayesian analysis for a wide class of conceptual climate models is possible. The results also highlight a problem with estimating the chronology of the climate record before further statistical analysis: a practice which is common in paleoclimate science. Using two data sets based on the same record but with different estimated chronologies results in conflicting conclusions about the importance of the astronomical forcing on the glacial cycle, and about the internal dynamics generating the glacial cycle, even though the difference between the two estimated chronologies is consistent with dating uncertainty. This highlights a need for chronology estimation and other inferential questions to be addressed in a joint statistical procedure.
In situ characterization of dolomite crystals: Evaluation of dolomitization process and its effect on zoning
Authors: Olanipekun Babatunde John , Azmy Karem
Published: March 2017

Dolomitization is a dissolution–re‐precipitation process which proceeds via micrometre‐scale interface reaction horizons. However, the effect of this fundamental local medium of replacement process on precipitated dolomite crystals is rarely investigated. For this purpose, dolomite samples of Ordovician Boat Harbour Formation carbonates (Newfoundland, Canada) from Main Brook and Daniel's Harbour (about 150 km apart) were studied. The investigation used high‐resolution approaches to carry out imaging and elemental analyses of individual dolomite crystals, including scanning electron microscopy, scanning electron microscopy‐based cathodoluminescence, secondary ion mass spectrometry and electron microprobe analysis. The purpose was to better understand geochemical variations across the crystal traverses and their association with dolomite replacement processes and conditions. The scanning electron microscopy‐based cathodoluminescence‐zoning character reveals three major crystal facies. Distinctly (planar boundaries) zoned core and indistinctly zoned core are zoned dolomite crystal facies in burial dolomite from Main Brook. Relatively unzoned crystal facies was identified in that of Daniel's Harbour. Compositionally zoned dolomite crystals are characterized by decreasing Sr, Na, Y and ∑REE but increasing Mn and Fe from core to rim sections. ‘Core to rim’ zoning was not found for major (Mg and Ca) elements. The zoning exhibited by the replacive dolomite crystals is interpreted to be, principally, a result of limited exchange between solutes of the bulk pore fluid and those of dissolving precursor marine carbonate. In tandem with petrographic features, the systematic compositional zoning character demonstrates that the effectiveness of the dolomitization process grades from indistinctly zoned core to relatively unzoned crystal facies via interface reaction horizons. Homogenization of major elements of core and rim sections, seen in distinctly zoned core crystal facies and to a much greater extent in relatively unzoned crystal facies, via a secondary reaction interface, is the first recognized stage of the ‘maturation process’ followed by homogenization of the trace elements seen largely in relatively unzoned crystal facies.
High physical fitness is associated with reduction in basal‐ and exercise‐induced inflammation
Authors: Kleiven Ø. , Bjørkavoll‐Bergseth M. , Melberg T. , Skadberg Ø. , Bergseth R. , Selvåg J. , Auestad B. , Aukrust P. , Aarsland T. , Ørn S.
Published: March 2017

C‐reactive protein (CRP) increases after strenuous exercise. It has been a concern that prolonged strenuous exercise may be harmful and induce a deleterious inflammatory response. The purpose of this study was to (a) assess and quantify the magnitude of CRP response following an endurance cycling competition in healthy middle‐aged recreational cyclists. (b) Identify important determinants of this response. (c) Identify the relationship between CRP, myocardial damage (cardiac Troponin I (cTnI)), and myocardial strain (B‐type natriuretic peptide [BNP]). (d) Identify the relationship between CRP and clinical events, defined as utilization of healthcare services or self‐reported unusual discomfort. Race time was used as a measure of physical fitness. A total of 97 individuals (43±10 years of age, 74 [76%] males) were assessed prior to and 0, 3, and 24 hours following the 91‐km mountain bike race “Nordsjørittet” (Sandnes, Norway, June 2013). There was a highly significant increase in CRP from baseline to 24 hours (0.9 (0.5‐1.8) mg/L vs. 11.6 (6.0‐17.5) mg/L (median[IQR]), P<.001), with no correlation of CRP to cTnI and BNP at any time‐point. CRP was strongly correlated to race time at baseline (r=.38, P<.001) and at 24 hours following the race (r=.43, P<.001), In multivariate models, race time was an independent predictor of CRP both at baseline and at 24 hours (P<.01). There was no relationship between CRP levels and clinical events. In conclusion, high physical fitness was associated with reduction in both basal‐ and exercise‐induced CRP. No adverse relationship was found between high intensity physical exercise, CRP levels, and outcomes.
Prevalence, age at onset, and risk factors of self‐reported asthma among Swedish adolescent elite cross‐country skiers
Authors: Eriksson L. M. , Irewall T. , Lindberg A. , Stenfors N.
Published: March 2017

The objective of the study was to compare the prevalence of self‐reported physician‐diagnosed asthma and age at asthma onset between Swedish adolescent elite skiers and a reference group and to assess risk factors associated with asthma. Postal questionnaires were sent to 253 pupils at the Swedish National Elite Sport Schools for cross‐country skiing, biathlon, and ski‐orienteering (“skiers”) and a random sample of 500 adolescents aged 16‐20, matched for sport school municipalities (“reference”). The response rate was 96% among the skiers and 48% in the reference group. The proportion of participants with self‐reported physician‐diagnosed asthma was higher among skiers than in the reference group (27 vs 19%, P=.046). Female skiers reported a higher prevalence of physician‐diagnosed asthma compared to male skiers (34 vs 20%, P=.021). The median age at asthma onset was higher among skiers (12.0 vs 8.0 years; P<.001). Female sex, family history of asthma, nasal allergy, and being a skier were risk factors associated with self‐reported physician‐diagnosed asthma. Swedish adolescent elite cross‐country skiers have a higher asthma prevalence and later age at asthma onset compared to a reference population. Being an adolescent, elite skier is an independent risk factor associated with asthma.
Localization of muscle damage within the quadriceps femoris induced by different types of eccentric exercises
Authors: Maeo S. , Saito A. , Otsuka S. , Shan X. , Kanehisa H. , Kawakami Y.
Published: March 2017

This study examined localization of muscle damage within the quadriceps femoris induced by different types of eccentric exercises by using transverse relaxation time (T2)‐weighted magnetic resonance imaging (MRI). Thirty‐three young males performed either of the following three exercises: single‐joint eccentric contraction of the knee extensors (KE), eccentric squat (S), or downhill walking (DW) (n=11/exercise). KE and S consisted of 5‐set×10‐lowering of 90% one‐repetition maximum load. DW was performed for 60 minutes with −10% slope, 6 km/h velocity, and 20% body mass load carried. At pre‐ and 24‐, 48‐, and 72‐hours post‐exercise, T2‐MRI was scanned and T2 values for the rectus femoris (RF), vastus intermedius (VI), vastus lateralis (VL), and vastus medialis (VM) at proximal, middle, and distal sites were calculated. Additionally, soreness felt when static pressure was applied to these sites and maximal isometric knee extension torque were measured. Maximal torque significantly (P<.05) decreased (7%‐15%) at 24‐48 hours after all exercises. T2 significantly increased (3%‐9%) at 24‐72 hours after all exercises, with heterogeneities within the muscles found in each exercise. Effect size and peak change of T2, as well as soreness, overall indicated that the proximal RF after KE and middle VM after S and DW were most affected by these exercises. The VL did not show any significant T2 increase after all exercises. These results suggest that muscle damage specifically localizes at the proximal RF by KE and at the middle VM by S and DW, while the VL is least damaged regardless of the exercises.
Externalizing an ‘Asset Model’ of Activation: Creative Institutional Work by Frontline Workers in the Norwegian Labour and Welfare Service
Authors: Håvold Ole Kristian Sandnes , Harsløf Ivan , Andreassen Tone Alm
Published: March 2017

The past two decades have brought significant shifts in Norwegian activation policy towards a joined‐up and employability‐enhancing approach to labour market inclusion in order to promote return‐to‐work despite health problems or disabilities. Utilizing a concept from health promotion, we term this approach an ‘asset model’ of activation. The Norwegian Labour and Welfare Service (NAV) and its local offices are the main agents implementing the new policy. This article aims to investigate the strategies that the frontline workers of NAV engage in, in order to externalize an ‘asset model’ in the adjacent medical field and to the general practitioners (GPs) in particular. We analyze these strategies as forms of creative institutional work – the purposive actions undertaken to change existing presumptions and opinions among relevant actors. We argue that although the new activation policy is not theirs to develop, in order to bring about changes in practice, ‘creating’ institutional work by the frontline workers is required. Our findings show that the frontline workers develop strategies in order to externalize an asset model to the GPs, as part of operationalizing an ‘activation’ reform into practice. We identify four forms of ‘creating’ institutional work undertaken by the frontline workers: ‘defining’ – enacting legislation and regulation in relation to GPs; ‘constructing normative networks’ – creating a more collaborative relationship with the GPs; ‘educating’ – teaching the GPs about the rules and regulations, and the opportunities and assistive measures they can offer to the injured; and thereby also ‘changing normative associations’ of GPs towards the activation policy.
Importin β1 targeting by hepatitis C virus NS3/4A protein restricts IRF3 and NF‐κB signaling of IFNB1 antiviral response
Authors: Gagné Bridget , Tremblay Nicolas , Park Alex Y. , Baril Martin , Lamarre Daniel
Published: March 2017

In this study, newly identified host interactors of hepatitis C virus (HCV) proteins were assessed for a role in modulating the innate immune response. The analysis revealed enrichment for components of the nuclear transport machinery and the crucial interaction with NS3/4A protein in suppression of interferon‐β (IFNB1) induction. Using a comprehensive microscopy‐based high‐content screening approach combined to the gene silencing of nuclear transport factors, we showed that NS3/4A‐interacting proteins control the nucleocytoplasmic trafficking of IFN regulatory factor 3 (IRF3) and NF‐κB p65 upon Sendai virus (SeV) infection. Notably, importin β1 (IMPβ1) knockdown—a hub protein highly targeted by several viruses—decreases the nuclear translocation of both transcription factors and prevents IFNB1 and IFIT1 induction, correlating with a rapid increased of viral proteins and virus‐mediated apoptosis. Here we show that NS3/4A triggers the cleavage of IMPβ1 and inhibits nuclear transport to disrupt IFNB1 production. Importantly, mutated IMPβ1 resistant to cleavage completely restores signaling, similar to the treatment with BILN 2061 protease inhibitor, correlating with the disappearance of cleavage products. Overall, the data indicate that HCV NS3/4A targeting of IMPβ1 and related modulators of IRF3 and NF‐κB nuclear transport constitute an important innate immune subversion strategy and inspire new avenues for broad‐spectrum antiviral therapies.
The effect of polydioxanone hemicerclage suture on the occurrence of fracture during tibial tuberosity advancement with an elongated bi‐directional hinged osteotomy
Authors: Bleakley Seth , Palmer Ross H. , Bresina Stephen , Roca Sy Ping , Tepic Slobodan
Published: March 2017

Objective

To investigate the effect of hemicerclage suture on the occurrence of fractures during advancement of an elongated bi‐directional hinged osteotomy (EBHO) for tibial tuberosity advancement (TTA) in dogs.

Study design

Experimental ex vivo study.

Animals

Canine cadavers (n = 14)

Methods

A uniform EBHO was performed in 28 cadaveric hind limbs (n = 28) from 14 skeletally mature, medium‐sized, mixed breed dogs. Paired limbs were randomly assigned with or without hemicerclage suture. The osteotomy was slowly spread (TTA) at a rate 1.5 mm every 15 seconds to a maximum distance of 24 mm or until a fracture was detected as an audible crack, visible propagation of the distal osteotomy or transverse fracture of the cortical bridge. The occurrence of fractures was compared between limbs with hemicerclage and without hemicerclage (control) suture using a chi‐square analysis. The advancement distance at the time of fracture was compared using a paired t test. A P value <.05 was considered significant.

Results

The cumulative occurrence of intraoperative fracture was significantly greater without hemicerclage than with hemicerclage at advancements of 12, 15, 18, and 24 mm. The mean (SD) spreading distance at the time of fracture was significantly less without hemicerclage at 16.85 (4.10) mm with a range of 12‐24 mm, than with hemicerclage at 20.62 (2.39) mm with a range of 18‐24 mm (P = .029).

Conclusion

The occurrence of immediate intraoperative fracture during advancement of an EBHO of the tibial tuberosity is less when a hemicerclage suture is placed.
Human IL‐6, IL‐17, IL‐1β, and TNF‐α differently regulate the expression of pro‐inflammatory related genes, tissue factor, and swine leukocyte antigen class I in porcine aortic endothelial cells
Authors: Gao Hanchao , Liu Lu , Zhao Yanli , Hara Hidetaka , Chen Pengfei , Xu Jia , Tang Jia , Wei Ling , Li Zesong , Cooper David K.C. , Cai Zhiming , Mou Lisha
Published: March 2017

Background

Pro‐inflammatory cytokines play important pathological effects in various diseases and allotransplantation; however, their pathological role in xenotransplantation remains elusive. In pig‐to‐human cell or organ transplantation, whether porcine cells or organs are activated by human cytokines or not as an important question needs to be investigated.

Methods

We investigated the effect of human IL‐6, IFN‐γ, IL‐17, IL‐1β, and TNF‐α in xenotransplantation using several in vitro models and porcine aortic endothelial cells (PAECs) as target cells. The downstream signaling pathways activated by these cytokines were studied with Western blotting, the regulation of the pro‐inflammatory related genes and pro‐coagulation factor were assessed using real‐time PCR or enzyme‐linked immunosorbent assay, and swine leukocyte antigen (SLA) class I and SLA class II DR were analyzed by flow cytometry.

Results

We found that NF‐κB and mitogen‐activated protein kinases (MAPKs) were activated by recombinant human IL‐17 (rhIL‐17), rhIL‐1β, and rhTNF‐α, while rhIL‐6 activated signal transducer and activator of transcription 3 (STAT3) in PAECs. The adhesion molecules (E‐selectin, VCAM‐1, and ICAM‐1), pro‐inflammatory gene (IL‐6), chemokines (IL‐8 and MCP‐1), and the pro‐coagulation factor (tissue factor) were induced by rhIL‐17, rhIL‐1β, and rhTNF‐α, while rhIL‐6 only increased the expression of MCP‐1 and tissue factor. Using flow cytometry analysis, SLA class I was upregulated in PAECs after exposure to rhIL‐1β and rhTNF‐α, but not rhIL‐6 or rhIL‐17, whereas SLA class II DR could not be induced by rhIL‐6, rhIL‐17, rhIL‐1β, or rhTNF‐α, although it could by recombinant porcine IFN‐γ (rpIFN‐γ). Although activation of PAECs by rhIL‐17 alone was not strong, rhIL‐17 combined with rhTNF‐α amplified the expression of E‐selectin, IL‐6, and IL‐8. Unexpectedly, we found that tocilizumab, a humanized anti‐human IL‐6 receptor antibody, could not block rhIL‐6‐mediated STAT3 activation in PAECs. Human IFN‐γ could not activate STAT1 or induce the downstream gene expression in PAECs, which was consistent with a previous report.

Conclusion

In conclusion, our data suggest that human IL‐6, IL‐17, IL‐1β, and TNF‐α significantly activate PAECs and are likely to promote inflammation and coagulation reaction in response to xenograft.
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

Background

Genetically 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.

Methods

Donor 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.

Results

The 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.

Conclusions

The 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.

Oculopharyngeal 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.
Estimación de la magnitud de la segregación escolar en América Latina
Authors: Murillo F. Javier , Martínez-Garrido Cynthia
Published: March 2017

Esta investigación busca estimar la magnitud del efecto de la segregación escolar socioeconómica, étnico-cultural y por procedencia inmigrante/nativo de los países de América Latina. Para ello, se realiza una explotación especial de la base de datos del Tercer estudio regional comparativo y explicativo, TERCE, del Laboratorio Latinoamericano de Evaluación de la Calidad de la Educación, LLECE (2013), de la Oficina Regional de Educación para América Latina y el Caribe de la Organización de las Naciones Unidas para la Educación, la Ciencia y la Cultura, OREALC/UNESCO, para estimar el índice de disimilitud a una muestra de 105.847 estudiantes de educación primaria en 5.733 escuelas de 15 países. Los resultados indican que la segregación escolar es muy alta en el conjunto de países de América Latina. La segregación escolar promedio por nivel socioeconómico es de 0,56, de carácter étnico es de 0,92, y por procedencia inmigrante/nativo de 0,80.
La escritura científica en las disciplinas: análisis del metadiscurso interpersonal en artículos científicos de química, biología y filosofía
Authors: Bonnet Marcela , González Daniela Soledad
Published: March 2017

Este artículo indaga, a través de un estudio comparativo entre artículos científicos, sobre cómo los autores se construyen en cuanto enunciadores académicos en diversas disciplinas. Se toman las categorías de metafunción interpersonal de Halliday y de metadiscurso de Hyland.

A partir de una metodología de análisis cualitativa, se analiza un corpus compuesto por tres series: serie A (artículos de filosofía), B (artículos de biología) y C (artículos de química).

Los resultados muestran que los artículos de filosofía presentan mitigadores y enfatizadores de modo homogéneo a lo largo de todo el texto, debido a la intención predominantemente argumentativa que existe en ellos; en cambio, en los artículos de biología y química, se registra una mayor presencia de modalizadores cuando se destaca la importancia del objeto por estudiar o cuando se discuten los resultados. Los artículos de filosofía presentan marcas de primera persona, no hallados en los textos de otras disciplinas.