bluuebunny/crossref_metadata_2025 huggingface dataset:
Caspase-(8/3) activation and organ inflammation in a rat model of resuscitated hemorrhagic shock: A role for uric acid
Authors: Gilbert Kim , Rousseau Guy , Bouchard Caroline , Dunberry-Poissant Sophie , Baril Frédérique , Cardinal Anne Marie , Khazoom François , Vega Melissa Aubin , Brochiero Emmanuelle , Charbonney Emmanuel
Published: December 2018

BACKGROUND

Multiple organ failure can develop after hemorrhagic shock (HS). Uric acid (UA) is released from dying cells and can be proinflammatory. We hypothesized that UA could be an alternative mediator of organ apoptosis and inflammation after HS.

METHODS

Ventilated male Wistar rats were used for the HS model. Two durations of shock (5 minutes vs. 60 minutes) were compared, and shams were instrumented only; animals were resuscitated and observed for 24 hours/72 hours. Caspases-(8/3), myeloperoxidase (MPO), TNF-α were measured in lungs and kidneys. Plasma UA and cytokine (IL-1β, IL-18, TNF-α) were measured. A second set of animals were randomized to vehicle versus Rasburicase intraperitoneal intervention (to degrade UA) during resuscitation. Another group received exogenous UA intraperitoneally without HS. Measures mentioned above, in addition to organs UA, were performed at 24 hours. In vitro, caspases-(8/3) activity was tested in epithelial cells exposed to UA.

RESULTS

Hemorrhagic shock increased organ (kidney and lung) TNF-α, MPO, and caspases activity in various patterns while caspase-8 remained elevated over time. Hemorrhagic shock led to increased plasma UA at 2 hours, which remained high until 72 hours; TNF-α and IL-18 were elevated at 24 hours. The exogenous UA administration in sham animals reproduced the activation of caspase-8 and MPO in organs, and TNF-α in the lung. The increased plasma and organ UA levels, plasma and lung TNF-α, as well as organ caspase-(8/3) and MPO, observed at 24 hours after HS, were prevented by the administration of Rasburicase during resuscitation. In vitro, soluble UA induced caspases-(3/8) activity in epithelial cells.

CONCLUSION

Uric acid is persistently high after HS and leads to the activation of caspases-8 and organ inflammation; these can be prevented by an intervention to degrade UA. Therefore, UA is an important biomarker and mediator that could be considered a therapeutic target during HS resuscitation in human.
Comparing short-, long-, and oblique-axis approaches to ultrasound-guided internal jugular venous catheterization: A meta-analysis of randomized controlled trials
Authors: Chen Jen-Yin , Wang Li-Kai , Lin Yao-Tsung , Lan Kuo-Mao , Loh El-Wui , Chen Chih-Heng , Tam Ka-Wai
Published: December 2018

BACKGROUND

Internal jugular venous catheterization is performed for numerous therapeutic interventions. Although ultrasound-guided internal jugular venous catheterization is the gold standard for this procedure, complications can still occur. Various scanning axes, namely, the short axis (SA), long axis (LA), and oblique axis (OA), have been developed to ameliorate these complications. This study compared the efficacy and safety of SA, LA, and OA approaches.

METHODS

PubMed, Embase, and Cochrane Library databases were searched for studies published before September 2018. Only randomized controlled trials were included. We conducted meta-analyses using a random-effects model. Treatment efficacy was measured by total success rate, first-pass success rate, number of needle passes, and incidence of complications, namely, arterial puncture, hematoma, and catheter-related bloodstream infection.

RESULTS

Six randomized controlled trials with 621 patients were included. No significant differences were observed in total success rate and first-pass success rate, as well as in the arterial puncture, hematoma, or catheter-related bloodstream infection complications between SA and LA approaches. Moreover, no significant difference was found between SA and OA approaches in terms of total success rate, first-pass success rate, number of needle passes, and complications of arterial puncture and hematoma. However, the number of needle passes was significantly fewer in SA approach than in LA approach (weighted mean difference, −0.18; 95% confidence interval, −0.35 to −0.01).

CONCLUSION

None of the scanning axes exhibited unique features that could enhance their suitability for application. Hence, scanning axes should be selected by considering various factors that include patient characteristics, clinician expertise, and ease of procedures.

LEVEL OF EVIDENCE

Systematic review and meta-analysis, level I.
The effectiveness of junctional tourniquets: A systematic review and meta-analysis
Authors: Smith Shane , White John , Wanis Kerollos Nashat , Beckett Andrew , McAlister Vivian C. , Hilsden Richard
Published: December 2018

BACKGROUND

Junctional tourniquets have been incorporated into tactical combat casualty care for junctional vascular trauma. They apply external compression to stop blood flow in the groin and axilla.

OBJECTIVES

The primary outcome was effectiveness in achieving arterial occlusion. Secondary outcomes included time to application and pain scores.

DATA SOURCES

Medline and EMBASE databases were searched.

Study Appraisal and Synthesis Methods

A random-effects meta-analysis was conducted to estimate the average effectiveness and time to effective application for each device.

RESULTS

Eight studies reported the effectiveness of junctional tourniquets in healthy volunteers. The average effectiveness was 52% (95% confidence interval [CI], 15–87%) for the abdominal application of the abdominal aortic and junctional tourniquet (AAJT), 83% (95% CI, 73–89%; 26%) for the junctional Emergency Treatment Tool, 87% (95% CI, 79–92%; 15%) for the SAM junctional tourniquet (SJT), and 95% (95% CI, 90–98%) for the Combat Ready Clamp. The groin application of the AAJT was studied in two articles with 100% in both studies. The average time to application was 101 seconds for the SAM junctional tourniquet (95% CI, 50–152 seconds) and the Combat Ready Clamp (95% CI, 63–139 seconds), while it was 130 seconds (95% CI, 85–176 seconds) for the Junctional Emergency Treatment Tool. The abdominal application of AAJT had an average time to application of 92 and 171 seconds in two studies.

LIMITATIONS

All studies were conducted in healthy volunteers.

CONCLUSION AND IMPLICATIONS

Junctional tourniquets may meet a medical need in combat, and in the civilian environment, to control hemorrhage from these difficult injuries. All four Food and Drug Administration–approved devices demonstrate the ability to achieve vascular occlusion in healthy volunteers; however, effectiveness in patient transport has not been evaluated, and outcomes of their use in the field need to be captured and reported.

LEVEL OF EVIDENCE

Systematic review, level III.
Symptomatic human immunodeficiency virus–infected patients have poorer outcomes following emergency general surgery: A study of the nationwide inpatient sample
Authors: Sandler Britt J. , Davis Kimberly A. , Schuster Kevin M.
Published: December 2018

BACKGROUND

The impact of human immunodeficiency virus (HIV) infection on outcomes following common emergency general surgery procedures has not been evaluated since the widespread introduction of highly active antiretroviral therapy.

METHODS

A retrospective cohort study was conducted using the Nationwide Inpatient Sample. Records of patients who underwent laparoscopic or open appendectomy, cholecystectomy, or colon resection after emergency admission from 2004 to 2011 were obtained. Outcomes analyzed included in-hospital mortality, length of stay, total charges, and selected postoperative complications. Patients were divided among three groups, HIV-negative controls, asymptomatic HIV-positive patients, and symptomatic HIV/acquired immune deficiency syndrome (AIDS) patients. Data were analyzed using χ2 and multivariable regression with propensity score matching among the three groups, with p value less than 0.05 significant.

RESULTS

There were 974,588 patients identified, of which 1,489 were HIV-positive and 1,633 were HIV/AIDS-positive. The HIV/AIDS patients were more likely to die during their hospital stay than HIV-negative patients (4.4% vs. 1.6%, adjusted odds ratio, 3.53; 95% confidence interval [CI], 2.67–4.07; p < 0.001). The HIV/AIDS patients had longer hospital stays (7 days vs. 3 days; adjusted difference, 3.66 days; 95% CI, 3.53–4.00; p < 0.001) and higher median total charges than HIV-negative patients (US $47,714 vs. US $28,405; adjusted difference, US $15,264; 95% CI, US $13,905–US $16,623; p < 0.001). The HIV/AIDS patients also had significantly increased odds of certain postoperative complications, including sepsis, septic shock, pneumonia, urinary tract infection, acute renal failure and need for transfusion (p < 0.05 for each). Differences persisted irrespective of case complexity and over the study period. Asymptomatic HIV-positive patients had outcomes similar to HIV-negative patients.

CONCLUSION

The HIV/AIDS patients have a greater risk of death, infectious, and noninfectious complications after emergency surgery regardless of operative complexity and despite advanced highly active antiretroviral therapy. Patients who have not developed advanced disease, however, have similar outcomes to HIV-negative patients.

LEVEL OF EVIDENCE

Prognostic and epidemiologic study, level III.
Development of a Predictive Model Using Endoscopic Features for Gastric Cytomegalovirus Infection in Renal Transplant Patients
Authors: Yeo Seong Jae , Kwon Ki Tae , Kim Eun Soo , Jung Min Kyu , Kim Sung Kook , Lee Hyun Seok , Lee Jun Seop , Lee Sang Won , Lee Yoo Jin , Kwak Sang Gyu , Han Seungyeup
Published: December 2018

Background.

Cytomegalovirus (CMV) is a common viral pathogen in transplant patients which often targets the stomach. However, the endoscopic characteristics of gastric CMV infection are not well established. We aimed to develop a predictive model using endoscopic findings for gastric CMV infection in renal transplant patients.

Methods.

A retrospective study of 287 kidney transplant recipients who underwent endoscopy with biopsy for suspected CMV infection from January 2006 to November 2015 at a tertiary referral hospital was performed. CMV infection was defined based on inclusion bodies in hematoxylin and eosin and immunohistochemical staining. Endoscopic and clinical parameters related to gastric CMV infection were selected by univariate analyses. Multivariate logistic regression was used to create a predictive model from β-coefficients.

Results.

CMV was present in 107 (37.7%) of the 287 patients. Multivariate analysis found age (odds ratio [OR], 0.964; 95% confidence interval [CI], 0.938-0.99; P = 0.008), erosions with surface exudate (OR, 5.34; 95% CI, 2.687-10.612; P < 0.001), raised shape of erosions (OR, 3.957; 95% CI, 1.937-8.083; P < 0.001), and antral location of ulcers (OR, 15.018; 95% CI, 5.728-39.371; P < 0.001) as independent predictive factors for gastric CMV infection. Using the predictive model created from this analysis, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 71.03%, 85.56%, 74.51%, 83.24%, and 80.14%, respectively. The area under the receiver operating characteristic curve of this model for detecting CMV infection was 0.850 (95% CI, 0.803-0.889; P < 0.001).

Conclusions.

The predictive model with typical endoscopic findings may be useful for detecting gastric CMV infection in renal transplant patients.
Subclinical Antibody-mediated Rejection After Kidney Transplantation: Treatment Outcomes
Authors: Parajuli Sandesh , Joachim Emily , Alagusundaramoorthy Sayee , Blazel Justin , Aziz Fahad , Garg Neetika , Muth Brenda , Mohamed Maha , Mandelbrot Didier , Zhong Weixong , Djamali Arjang
Published: December 2018

Background.

Antibody-mediated rejection (AMR) is a leading cause of morbidity and mortality after kidney transplantation. Early diagnosis and treatment of subclinical AMR based on the donor-specific antibody (DSA) testing may result in better outcomes.

Methods.

We tested this hypothesis in 220 kidney transplant recipients who underwent an indication or DSA-based surveillance protocol biopsies between March 1, 2013 and December 31, 2016. Patients were divided into 3 groups: clinical AMR (n = 118), subclinical AMR (n = 25), or no rejection on protocol biopsy (controls; n = 77).

Results.

Both clinical and subclinical AMR groups underwent similar treatment including plasmapheresis, pulse steroids, IVIG, and rituximab (P = ns). Mean follow-up after AMR was 29.5 ± 16.8 months. There were 2 (3%), 2 (8%), and 54 (46%) death-censored graft failures in the control, subclinical, and clinical AMR groups, respectively (P < 0.001). Graft outcomes were similar in the subclinical rejection and control groups. In adjusted Cox regression analysis, only clinical rejection (hazards ratio [HR], 4.31; 95% confidence interval [CI], 1.01-18.94; P = 0.05) and sum chronicity scores (HR, 1.16; 95% CI, 1.01-1.35; P = 0.03) were associated with increased risk of graft failure, while estimated glomerular filtration rate at time of biopsy (HR, 0.98; 95% CI, 0.96-0.99; P = 0.01) was associated with decreased risk of graft failure.

Conclusions.

Our study suggests that early diagnosis and treatment of subclinical AMR using DSA monitoring may improve outcomes after kidney transplantation.
Functional Microbiomics in Liver Transplantation: Identifying Novel Targets for Improving Allograft Outcomes
Authors: Kriss Michael , Verna Elizabeth C. , Rosen Hugo R. , Lozupone Catherine A.
Published: December 2018

Gut dysbiosis, defined as a maladaptive gut microbial imbalance, has been demonstrated in patients with end-stage liver disease, defined as a contributor to disease progression, and associated clinically with severity of disease and liver-related morbidity and mortality. Despite this well-recognized phenomena in patients with end-stage liver disease, the impact of gut dysbiosis and its rate of recovery following liver transplantation (LT) remains incompletely understood. The mechanisms by which alterations in the gut microbiota impact allograft metabolism and immunity, both directly and indirectly, are multifactorial and reflect the complexity of the gut-liver axis. Importantly, while research has largely focused on quantitative and qualitative changes in gut microbial composition, changes in microbial functionality (in the presence or absence of compositional changes) are of critical importance. Therefore, to translate functional microbiomics into clinical practice, one must understand not only the compositional but also the functional changes associated with gut dysbiosis and its resolution post-LT. In this review, we will summarize critical advances in functional microbiomics in LT recipients as they apply to immune-mediated allograft injury, posttransplant complications, and disease recurrence, while highlighting potential areas for microbial-based therapeutics in LT recipients.
Identification of human genetic variants controlling circular RNA expression
Authors: Ahmed Ikhlak , Karedath Thasni , Al-Dasim Fatima M. , Malek Joel A.
Published: December 2018

Circular RNAs (circRNAs) are abundant in eukaryotic transcriptomes and have been linked to various human disorders. However, understanding genetic control of circular RNA expression is in early stages. Here we present the first integrated analysis of circRNAs and genome sequence variation from lymphoblastoid cell lines of the 1000 genomes project. We identified thousands of circRNAs in the RNA-seq data and show their association with local single nucleotide polymorphic sites, referred to as circQTLs, which influence the circRNA transcript abundance. Strikingly, we found that circQTLs exist independently of eQTLs with most circQTLs having no effect on mRNA expression. Only a fraction of the polymorphic sites are shared and linked to both circRNA and mRNA expression with mostly similar effects on circular and linear RNA. A shared intronic QTL, rs55928920, of HMSD gene drives the circular and linear expression in opposite directions, potentially modulating circRNA levels at the expense of mRNA. Finally, circQTLs and eQTLs are largely independent and exist in separate linkage disequilibrium (LD) blocks with circQTLs highly enriched for functional genomic elements and regulatory regions. This study reveals a previously uncharacterized role of DNA sequence variation in human circular RNA regulation.
Dynamically Evolving Cell Sizes During Early Development Enable Normal Gastrulation Movements In Zebrafish Embryos
Authors: Menon Triveni , Borbora Asfa Sabrin , Kumar Rahul , Nair Sreelaja
Published: December 2018

Current knowledge of the mechanisms of cell migration is based on differentiated cells in culture where it is known that the actomyosin machinery drives migration via dynamic interactions with the extracellular matrix and adhesion complexes. However, unlike differentiated cells, cells in early metazoan embryos must also dynamically change cell sizes as they migrate. The relevance of cell size to cell migration and embryonic development is not known. Here we investigate this phenomena in zebrafish embryos, a model system in which reductive cell divisions causes cell sizes to decrease naturally over time as cells migrate collectively to sculpt the embryonic body plan. We show that cell size reduction during early development follows power-law scaling. Because mutations that can perturb cell sizes so early in development do not exist, we generate haploid and tetraploid zebrafish embryos and show that cell sizes in such embryos are smaller and larger than the diploid norm, respectively. Cells in embryos made of smaller or larger than normal cells migrate sub-optimally, leading to gastrulation defects. Multiple lines of evidence suggest that the observed defects originate from altered cell size rather than from pleotropic effects of altered ploidy. This interpretation is strengthened by the result wherein restoring cell sizes to normal diploid-like values rescues gastrulation defects. Live imaging of chimeric embryos where haploid/tetraploid cells are introduced into diploid embryos reveal the cell-autonomous nature of the migration defects. Additionally, aberrant intracellular actin dynamics with respect to the vectorial direction of motion suggests a cellular mechanism behind the migration defects. Taken together, early reductive cell divisions potentially allow dynamic, stage-specific cell size norms to emerge, which enables efficient collective cell migration to correctly position cells in space and time to shape an amorphous ball of blastoderm into an embryo.
Multidimensional analysis of Gammaherpesvirus RNA expression reveals unexpected heterogeneity of gene expression
Authors: Oko Lauren M. , Kimball Abigail K. , Kaspar Rachael E. , Knox Ashley N. , Coleman Carrie B. , Rochford Rosemary , Chang Tim , Alderete Benjamin , Dyk Linda F. van , Clambey Eric T.
Published: December 2018

Virus-host interactions are frequently studied in bulk cell populations, obscuring cell-to-cell variation. Here we investigate endogenous herpesvirus gene expression at the single-cell level, combining a sensitive and robust fluorescent in situ hybridization platform with multiparameter flow cytometry, to study the expression of gammaherpesvirus non-coding RNAs (ncRNAs) during lytic replication, latent infection and reactivation in vitro. This method allowed robust detection of viral ncRNAs of murine gammaherpesvirus 68 (γHV68), Kaposi’s sarcoma associated herpesvirus and Epstein-Barr virus, revealing variable expression at the single-cell level. By quantifying the inter-relationship of viral ncRNA, viral mRNA, viral protein and host mRNA regulation during γHV68 infection, we find heterogeneous and asynchronous gene expression during latency and reactivation, with reactivation from latency identified by a distinct gene expression profile within rare cells. Further, during lytic replication with γHV68, we find many cells have limited viral gene expression, with only a fraction of cells showing robust gene expression, dynamic RNA localization, and progressive infection. Lytic viral gene expression was enhanced in primary fibroblasts and by conditions associated with enhanced viral replication, with multiple subpopulations of cells present in even highly permissive infection conditions. These findings, powered by single-cell analysis integrated with automated clustering algorithms, suggest inefficient or abortive γHV infection in many cells, and identify substantial heterogeneity in viral gene expression at the single-cell level.

AUTHOR SUMMARY

The gammaherpesviruses are a group of DNA tumor viruses that establish lifelong infection. How these viruses infect and manipulate cells has frequently been studied in bulk populations of cells. While these studies have been incredibly insightful, there is limited understanding of how virus infection proceeds within a single cell. Here we present a new approach to quantify gammaherpesvirus gene expression at the single-cell level. This method allows us to detect cell-to-cell variation in the expression of virus non-coding RNAs, an important and understudied class of RNAs which do not encode for proteins. By examining multiple features of virus gene expression, this method further reveals significant variation in infection between cells across multiple stages of infection, even in conditions generally thought to be highly uniform. These studies emphasize that gammaherpesvirus infection can be surprisingly heterogeneous when viewed at the level of the individual cell. Because this approach can be broadly applied across diverse viruses, this study affords new opportunities to understand the complexity of virus infection within single cells.
Alternative Promoters Drive Human Cytomegalovirus Reactivation from Latency
Authors: Collins-McMillen Donna , Rak Mike , Buehler Jason , Igarashi-Hayes Suzu , Kamil Jeremy , Moorman Nat , Goodrum Felicia
Published: December 2018

Reactivation from latency requires reinitiation of viral gene expression and culminates in the production of infectious progeny. The major immediate early promoter (MIEP) of human cytomegalovirus (HCMV) drives the expression of crucial lytic cycle transactivators but is silenced during latency in hematopoietic progenitor cells (HPCs). Because the MIEP is poorly active in HPCs, it is unclear how viral transactivators are expressed during reactivation. We demonstrate that transcripts originating from alternative promoters within the canonical major immediate early locus are abundantly expressed upon reactivation, whereas MIEP-derived transcripts remain undetectable. Further, we show that these promoters are necessary for efficient reactivation in primary CD34+ HPCs. Our findings change the paradigm for HCMV reactivation by demonstrating that promoter switching governs reactivation from viral latency in a context-specific manner.
Extracellular Matrix acts as pressure detector in biological tissues
Authors: Dolega Monika E. , Brunel Benjamin , Goff Magali Le , Greda Magdalena , Verdier Claude , Joanny Jean-François , Recho Pierre , Cappello Giovanni
Published: December 2018

Imposed deformations play an important role in morphogenesis and tissue homeostasis, both in normal and pathological conditions 1–5. To perceive mechanical perturbations of different types and magnitudes, tissues need a range of appropriate detectors 6–8, with a compliance that has to match the perturbation amplitude. As a proxy of biological tissues, we use multicellular aggregates, a composite material made of cells, extracellular matrix and permeating fluid. We compare the effect of a selective compression of cells within the aggregate, leaving the extracellular matrix unstrained, to a global compression of the whole aggregate. We show that the global compression strongly reduces the aggregate volume 9–13, while the same amount of selective compression on cells has almost no effect 14,15. We support this finding with a theoretical model of an actively pre-stressed composite material, made of incompressible and impermeable cells and a poroelastic interstitial space. This description correctly predicts the emergent bulk modulus of the aggregate as well as the hydrodynamic diffusion coefficient of the percolating interstitial fluid under compression. We further show that, on a longer timescale, the extracellular matrix serves as a sensor that regulates cell proliferation and migration in a 3D environment through its permanent deformation and dehydration following the global compression.
CSR and sustainability reporting practices in India: an in-depth content analysis of top-listed companies
Authors: Aggarwal Priyanka , Singh Ajay Kumar
Published: December 2018

Purpose

The purpose of this paper is to comprehensively analyze the corporate social responsibility (CSR) and sustainability reporting (SR) practices of Indian companies in terms of disclosure quantity and quality, and to investigate the differences in SR practices by SR dimension, industry, ownership structure, firm size and profitability.

Design/methodology/approach

Data are collected from annual reports/business responsibility reports (BRR)/CSR/sustainability reports of 60 top-listed companies in India. A comprehensive sustainability reporting index is developed. Content analysis technique is used. Inter-coder reliability is established.

Findings

Altogether, 18 items of the index are not disclosed by the majority of companies in India. SR quality is found significantly lower than the SR quantity. Moreover, SR practices significantly differ by dimension/category, industry-type and firm-size but are not influenced by ownership structure. However, the study fails to establish any conclusive relationship between SR and profitability.

Practical implications

The present study has several implications for corporates, practitioners, policymakers and stakeholders. The findings underscore the need for amendments in the Global Reporting Initiative guidelines and BRR framework of the Securities and Exchange Board of India to avoid patchy disclosures and ensure complete reporting by companies.

Originality/value

This study is among the foremost studies in India evaluating SR practices of top-listed companies in the wake of the mandatory BRR requirement from a quantitative as well as qualitative perspective using a multidimensional index.
Cutaneous adult xanthogranuloma with a small portion of BRAFV600E mutated Langerhans cell histiocytosis populations: A case report and the review of published work
Authors: Ishikawa Mai , Endo Yukie , Uehara Akihito , Suto Mariko , Yasuda Masahito , Motegi Sei‐ichiro , Ishikawa Osamu
Published: December 2018

Histiocytoses, including Langerhans cell histiocytosis (LCH), juvenile or adult xanthogranuloma (AXG) and Rosai–Dorfman disease (RDD), are rare disorders characterized by the proliferation of cells derived from monocyte/macrophage lineages. A few cases of LCH coexisting with xanthogranuloma or RDD have been reported. The etiology of these diseases remains unclear. However, oncogenic BRAFV600E mutations have been identified in LCH. Here, we report the case of a 26‐year‐old Japanese man with a 3‐month history of a solitary occipital nodule. No abnormality was detected in his other organs, and a total resection of the nodule was performed. Histopathological examination revealed the coexistence of LCH and AXG with prominent emperipolesis characteristic of RDD. Immunohistochemistry showed that most of the large histiocytes were positive for CD68, weakly positive or negative for S100, and negative for CD207 and CD1a, supporting the diagnosis of AXG. The tumor cells with emperipolesis did not show S100‐positive findings characteristic of RDD. The focally aggregated oval histiocytic cells were positive for CD1a, CD207, CD68 and S100, and were compatible with the immunophenotype of LCH cells. In addition, these cells were positive for BRAFV600E mutation. The tumor cells in our patient exhibited a cellular morphology characteristic of multiple histiocytoses in a solitary cutaneous nodule, which may imply an etiological association among LCH, AXG and RDD. To our knowledge, this is the first report of a BRAFV600E mutation‐positive case of LCH coexisting with AXG. Because patients with BRAFV600E mutation have higher risks of multisystemic LCH and recurrence, we should carefully follow up the patient.
Interactions among trees: A key element in the stabilising effect of species diversity on forest growth
Authors: Aussenac Raphaël , Bergeron Yves , Gravel Dominique , Drobyshev Igor
Published: December 2018

There is mounting evidence that species diversity increases the temporal stability of forest growth. This stabilising effect of diversity has mainly been attributed to species differences in their response to fluctuating environmental conditions. Interactions among individuals could also contribute to the stabilising effect of diversity by increasing the mean and reducing the variance of tree growth, however, this has never been directly demonstrated.

We used tree‐ring width chronologies from temperate and boreal mixed stands of Eastern Canada to identify the role of interactions among individuals in the stabilising effect of diversity on forest growth. Using neighbourhood competition index and a mixed model, we compared the effect of interspecific and intraspecific interactions on the mean and the variance of tree growth.

We found that interspecific interactions are less detrimental to tree growth than intraspecific interactions. We also found that interspecific interactions buffer tree response to drought and thereby reduce the variance of tree growth.

Our results indicate diversity may increase the mean and reduce the variance of tree growth through interactions among individuals. Thus, we demonstrate interactions among individuals play a role in the stabilising effect of diversity on forest growth, and in doing so, we bring to light other mechanisms of the insurance hypothesis.

Aplain language summaryis available for this article.
Maternal diet and age alter direct and indirect relationships between life‐history traits across multiple generations
Authors: Goos Jared M. , Swain Cameron J. , Munch Stephan B. , Walsh Matthew R.
Published: December 2018

Maternal age has important consequences for offspring fitness, with influences on size, development and reproductive schedules. Such maternal age effects may be driven by differential provisioning of resources; yet, little is known about the role of environmental supply of nutritional resources in mediating such effects.

We tested the influence of limiting nutritional resource, dietary phosphorus (P), on maternal age effects across multiple generations by examining the potential interactive effects of maternal nutrition and age on daughter and granddaughter life‐history traits in the freshwater crustacean Daphnia pulicaria.

Maternal age and diet had significant but contrasting effects on offspring life history. We did not observe any evidence that age effects on offspring life history are mediated by maternal diet. However, granddaughter growth and size at maturation were influenced by the interaction between grandmaternal age and diet, suggesting that the appearance of transgenerational effects of age and diet were delayed by one generation.

Because offspring life history is often linked directly and/or indirectly to life history variation in previous generations, we utilized structural equation modelling (SEM) to assess such direct or indirect relationships.

SEM revealed striking differences in the relationship between growth, development time and fecundity both within and among generations, depending on the age and diet in the F0 generation. Interestingly, direct and persistent relationships between the F0 generation and the F2 generation are most prevalent when grandmothers are old and fed low P diets, and such relationships are largely driven by fecundity in the F0 generation. Additionally, indirect causal relationships between the F0 generation and F2 generation are most pronounced when grandmothers are young and fed low P diets or when grandmothers are old and fed high P diets.

Our results indicate that transgenerational effects of maternal age and environment persist across multiple generations, and vary between successive generations. Further, our examination of the interaction network between life‐history traits of each generation suggest that the mechanisms for such persistent transgenerational effects are highly dependent on maternal condition.

A plain language summary is available for this article.
Catch diversification provides multiple benefits in inland fisheries
Authors: Matsuzaki Shin‐Ichiro S. , Shinohara Ryuichiro , Uchida Kei , Sasaki Takehiro
Published: December 2018

Diversification of fisheries and agroecosystems can increase and stabilize production and revenue, despite unpredictable changes in ecosystems and markets. Recent work suggests that diversification can provide multiple benefits simultaneously, but empirical evidence of relationships between catch or crop diversification and the provision of multiple benefits is scarce. The effect of diversification on multiple benefits may vary temporally and among systems.

Using long‐term (11–54 years) capture fishery statistics from five Japanese lakes, we examined whether catch diversity increased multiple benefits, including revenue, nitrogen and phosphorus removal, and seasonal commercial species diversity. We also assessed whether catch species diversity increased the stability of each benefit via a portfolio effect (PE).

Our study revealed positive relationships between catch diversity and the bundle of benefits (the mean of all normalized benefits; i.e., the provisioning of multiple benefits) in all five lakes, even after controlling for the total catch. The effects of catch diversity on individual benefits were positive or insignificant and differed among the study lakes. These differences were likely caused by the range and variation of functional characteristics among catch species. The influence of the annual mean price on revenue suggested that market forces did have an effect.

We also found that aggregated revenue as well as N and P removal were 1.6–2.1 times (four lakes), 1.5–2.2 times (four lakes), and 1.4–2.2 times (all five lakes) more stable, respectively, than would be expected if only a single species were harvested. This greater stability suggests that maintaining catch species diversity may increase the stability of multiple benefits through PEs.

Synthesis and applications. Our analysis suggests that catch diversification has great potential to increase the magnitude and stability of multiple benefits. Although total catch alone was sufficient to provide multiple benefits, a goal of maximization with specialization may decrease stability and deplete resources. Under fluctuating environmental and economic conditions, diversification strategies promise to be a potential management option for achieving resilient and sustainable inland fisheries.
Diet and diet‐associated bacteria shape early microbiome development in Yellowtail Kingfish (Seriola lalandi)
Authors: Wilkes Walburn Jackson , Wemheuer Bernd , Thomas Torsten , Copeland Elizabeth , O'Connor Wayne , Booth Mark , Fielder Stewart , Egan Suhelen
Published: December 2018

The supply of quality juveniles via land‐based larviculture represents a major bottleneck to the growing finfish aquaculture industry. As the microbiome plays a key role in animal health, this study aimed to assess the microbial community associated with early larval development of commercially raised Yellowtail Kingfish (Seriola lalandi). We used qPCR and 16S rRNA gene amplicon sequencing to monitor changes in the microbiome associated with the development of S. lalandi from larvae to juveniles. We observed an increase in the bacterial load during larval development, which consisted of a small but abundant core microbiota including taxa belonging to the families Rhodobacteraceae, Lactobacillaceae and Vibrionaceae. The greatest change in the microbiome occurred as larvae moved from a diet of live feeds to formulated pellets, characterized by a transition from Proteobacteria to Firmicutes as the dominant phylum. A prediction of bacterial gene functions found lipid metabolism and secondary metabolite production were abundant in the early larval stages, with carbohydrate and thiamine metabolism functions increasing in abundance as the larvae age and are fed formulated diets. Together, these results suggest that diet is a major contributor to the early microbiome development of commercially raised S. lalandi.
In‐depth comparative analysis of Illumina® MiSeq run metrics: Development of a wet‐lab quality assessment tool
Authors: Kastanis George John , Santana‐Quintero Luis V. , Sanchez‐Leon Maria , Lomonaco Sara , Brown Eric W. , Allard Marc W.
Published: December 2018

Whole genome sequencing of bacterial isolates has become a daily task in many laboratories, generating incredible amounts of data. However, data acquisition is not an end in itself; the goal is to acquire high‐quality data useful for understanding genetic relationships. Having a method that could rapidly determine which of the many available run metrics are the most important indicators of overall run quality and having a way to monitor these during a given sequencing run would be extremely helpful to this effect. Therefore, we compared various run metrics across 486 MiSeq runs, from five different machines. By performing a statistical analysis using principal components analysis and a K‐means clustering algorithm of the metrics, we were able to validate metric comparisons among instruments, allowing for the development of a predictive algorithm, which permits one to observe whether a given MiSeq run has performed adequately. This algorithm is available in an Excel spreadsheet: that is, MiSeq Instrument & Run (In‐Run) Forecast. Our tool can help verify that the quantity/quality of the generated sequencing data consistently meets or exceeds recommended manufacturer expectations. Patterns of deviation from those expectations can be used to assess potential run problems and plan preventative maintenance, which can save valuable time and funding resources.
Mapping Biliteracy Teaching in Indigenous Contexts: From Student Shyness to Student Voice
Authors: Hornberger Nancy H. , Kvietok Dueñas Frances
Published: December 2018

Drawing on an ethnographic monitoring engagement with Kichwa intercultural bilingual educators in the Peruvian Amazon, we argue for ethnographic monitoring as a method and the continua of biliteracy as a heuristic for mapping biliteracy teaching in Indigenous contexts of bilingualism. Through our mapping, we uncover tensions in the teaching of majoritized languages in Indigenous contexts of postcoloniality, challenge constructs of student shyness, and propose pedagogies to support the flourishing of student voice in bilingual education.
A Campus Fractured: Neoliberalization and the Clash of Academic Democracies in France
Authors: Thorkelson Eli
Published: December 2018

Through an ethnographic case study of campus politics at a Parisian university, this paper shows that neoliberal university reforms in France failed to create neoliberal subjectivities. Instead, the reforms provoked conflicts between direct and representative democracy, traditions which had organized post‐1960s French university culture. These conflicts suggest that we can decenter neoliberalism and instead examine the confluence of multiple modes of academic production, along with the antagonistic emergence of non‐neoliberal subjectivities.
Comprehensive characterization of horse genome variation by whole‐genome sequencing of 88 horses
Authors: Jagannathan V. , Gerber V. , Rieder S. , Tetens J. , Thaller G. , Drögemüller C. , Leeb T.
Published: December 2018

Whole‐genome sequencing studies are vital to gain a thorough understanding of genomic variation. Here, we summarize the results of a whole‐genome sequencing study comprising 88 horses and ponies from diverse breeds at 19.1× average coverage. The paired‐end reads were mapped to the current EquCab3.0 horse reference genome assembly, and we identified approximately 23.5 million single nucleotide variants and 2.3 million short indel variants. Our dataset included at least 7 million variants that were not previously reported. On average, each individual horse genome carried ∼5.7 million single nucleotides and 0.8 million small indel variants with respect to the reference genome assembly. The variants were functionally annotated. We provide two examples for potentially deleterious recessive alleles that were identified in a heterozygous state in individual genome sequences. Appropriate management of such deleterious recessive alleles in horse breeding programs should help to improve fertility and reduce the prevalence of heritable diseases. This comprehensive dataset has been made publicly available, will represent a valuable resource for future horse genetic studies and supports the goal of accelerating the rates of genetic gain in domestic horse.
Chemically modified peanut extract shows increased safety while maintaining immunogenicity
Authors: van der Kleij Hanneke P. M. , Warmenhoven Hans J. M. , van Ree Ronald , Versteeg Serge A. , Pieters Raymond H. H. , Dreskin Stephen C. , Knulst André C. , van Hoffen Els , Opstelten Dirk Jan E. , Koppelman Stef J. , Smit Joost J.
Published: December 2018

Background

Peanuts are most responsible for food‐induced anaphylaxis in adults in developed countries. An effective and safe immunotherapy is urgently needed. The aim of this study was to investigate the immunogenicity, allergenicity, and immunotherapeutic efficacy of a well‐characterized chemically modified peanut extract (MPE) adsorbed to Al(OH)3.

Methods

Peanut extract (PE) was modified by reduction and alkylation. Using sera of peanut‐allergic patients, competitive IgE‐binding assays and mediator release assays were performed. The immunogenicity of MPE was evaluated by measuring activation of human PE‐specific T‐cell lines and the induction of PE‐specific IgG in mice. The safety and efficacy of MPE adsorbed to Al(OH)3 was tested in two mouse models by measuring allergic manifestations upon peanut challenge in peanut‐allergic mice.

Results

Compared to PE, the IgE‐binding and capacity to induce allergic symptoms of MPE were lower in all patients. PE and MPE displayed similar immunogenicity in vivo and in vitro. In mice sensitized to PE, the threshold for anaphylaxis (drop in BT) upon subcutaneous challenge with PE was 0.01 mg, while at 0.3 mg MPE no allergic reaction occurred. Anaphylaxis was not observed when PE and MPE were fully adsorbed to Al(OH)3. Both PE and MPE + Al(OH)3 showed to be efficacious in a model for immunotherapy.

Conclusion

In our studies, an Al(OH)3 adsorbed MPE showed reduced allergenicity compared to unmodified PE, while the efficacy of immunotherapy is maintained. The preclinical data presented in this study supports further development of modified peanut allergens for IT.
Paediatric community‐acquired bacteraemia, pneumococcal invasive disease and antibiotic resistance fell after the pneumococcal conjugate vaccine was introduced
Authors: Berger Yael , Adler Amos , Ariel Tenenbaum , Rokney Assaf , Averbuch Diana , Grisaru‐Soen Galia
Published: December 2018

Aim

This study examined the impact of the routine pneumococcal conjugate vaccination (PCV) on childhood community‐acquired bacteraemia (CAB) and antibiotic resistance patterns in Israeli children.

Methods

Israel added the PCV vaccine to its national immunisation programme in July 2009. We retrospectively analysed the medical records of all patients with CAB under 18 years at three children's hospitals in Tel Aviv and Jerusalem from 2007 to 2015. The microbiological data, clinical presentation, pneumococcal serotype distribution, antibiotic susceptibility and outcomes of infections were compared before and after the vaccine was introduced.

Results

There were 511 904 emergency department visits and 125 922 children were hospitalised. Of those, 238 had CAB before vaccination was introduced (mean age 17 months) and 316 had CAB after the introduction (mean age 21 months). Emergency department presentations for CAB fell from 141.8 to 91.8 per 100 000 visits: a relative risk reduction (RRR) of 35%. Hospitalisations for CAB decreased from 430 to 337 per 100 000 admissions: an RRR of 22%. Hospitalisations due to Staphylococcus aureus increased significantly and penicillin nonsusceptible blood Streptococcus pneumoniae isolates decreased significantly.

Conclusion

Introducing national pneumococcal conjugate vaccination significantly changed the epidemiology of CAB, with reduced antibiotic‐resistant Streptococcus pneumoniae and increased hospitalisation rates for Staphylococcus aureus infections.
Mitophagy imbalance in cardiomyocyte ischaemia/reperfusion injury
Authors: Li Yu‐zhen , Wu Xu‐dong , Liu Xiu‐hua , Li Pei‐feng
Published: December 2018

The rhythmic contraction of cardiomyocytes consumes a lot of energy. 90% of ATP in cardiomyocytes is produced by mitochondria. Maintenance of a healthy population of mitochondria by mitophagy is critical for cardiomyocyte survival and normal function. Mitophagy refers to selective removal of damaged mitochondria by autophagy mechanism. The process of mitophagy must be restricted to dysfunctional mitochondria and maintained at a balanced level. Disruption in the balance inevitably leads to cardiomyocyte injury and dysfunction. Accumulating evidence suggests that mitophagy plays a pivotal role in ischaemia/reperfusion‐induced cardiomyocyte injury. In this review, we focus on the current understanding of mitophgy in cardiomyocyte function, the implications for cardiomyocyte injury in response to ischaemia/reperfusion as well as their underlying potential mechanisms.
Changes in spatial structures of plant communities lead to functional homogenization in an urban forest park
Authors: Bergeron Alexandre , Lavoie Claude , Domon Gérald , Pellerin Stéphanie
Published: December 2018

Aims

We investigated whether biotic homogenization of plant communities occurs over three decades in a small urban protected forest, and what the possible drivers are underlying the observed changes.

Location

A 96 ha temperate forest, Montréal, Canada.

Methods

We surveyed vegetation and explanatory variables (ecological conditions, disturbances, spatial structure) in 62 plant communities in 1980 and 2011. We collected plant attributes to identify functional groups (FGs). We evaluated changes in beta diversity using tests for homogeneity of multivariate dispersions. We used space–time interaction models to assess changes in FGs spatial structures. We used multivariate analyses to identify relationship between spatial patterns and explanatory variables, and variation partitioning analyses to identify the drivers involved in beta diversity changes.

Results

Beta diversity declined only in the herb–shrub communities. About 35% of their FGs had significantly changed their spatial distribution over time. Those that contracted their distribution were mainly composed of plants with wind‐dispersed seeds or with low to intermediate vegetative propagation capabilities, while those that expanded were plants with fleshy fruits or extensive vegetative propagation capabilities. In 1980, communities were structured into small isolated clumps, while in 2011, clumps expanded and coalesced near disturbed areas. In 1980, the spatial assembly processes relied essentially on endogenous factors while in 2011 exogenous factors, such as disturbances, became more influential. Multivariate analyses suggested that edge effect, past agricultural disturbances, and beaver activities facilitated the decrease of beta diversity (homogenization process).

Conclusions

The homogenization of herb–shrub communities likely resulted from changes in their clumped spatial structure. FGs with the most adapted attributes to disperse under urban forest conditions were those that expanded spatially. Structural changes seem to have begun with an unpredictable stage governed by dispersal limitation processes, followed by a predictable stage mostly driven by land‐use legacy and disturbances.