bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of connective tissue grafting on peri‐implant tissue in single immediate implant sites: A RCT
Authors: Zuiderveld Elise G. , Meijer Henny J. A. , den Hartog Laurens , Vissink Arjan , Raghoebar Gerry M.
Published: September 2017

Aim

To assess the effect of connective tissue grafting on the mid‐buccal mucosal level (MBML) of immediately placed and provisionalized single implants in the maxillofacial aesthetic zone.

Materials and methods

Sixty patients with a failing tooth were provided with an immediately placed and provisionalized implant. During implant placement, patients randomly received either a connective tissue graft from the maxillary tuberosity (n = 30, test group) or no graft (n = 30, control group). Follow‐up visits were at one (T1) and twelve months (T12) after final crown placement. The primary outcome measure was any change in MBML compared to the pre‐operative situation. In addition, gingival biotype, aesthetics (using the Pink Esthetic Score–White Esthetic Score), marginal bone level, soft tissue peri‐implant parameters and patient satisfaction were assessed.

Results

The mean MBML change at T12 was −0.5 ± 1.1 mm in the control group and 0.1 ± 0.8 mm in the test group (p = .03). No significant differences regarding other outcome variables were observed, neither was gingival biotype associated with a gain or loss in MBML.

Conclusions

This one‐year study shows that connective tissue grafting in single, immediately placed and provisionalized implants leads to less recession of the peri‐implant soft tissue at the mid‐buccal aspect, irrespective of the gingival biotype (www.trialregister.nl: TC3815).
Addition of albumin to Traditional Risk Score Improved Prediction of Mortality in Individuals Undergoing Transcatheter Aortic Valve Replacement
Authors: Grossman Yoni , Barbash Israel M. , Fefer Paul , Goldenberg Ilan , Berkovitch Anat , Regev Ehud , Fink Noam , Ben‐Zekry Sagit , Brodov Yafim , Kogan Alexander , Guetta Victor , Raanani Ehud , Segev Amit
Published: September 2017

Objectives

The ability of the Society of Thoracic Surgeons (STS) and European System for Cardiac Operative Risk Evaluation (EuroSCORE)‐2 scores to predict outcomes after transcatheter aortic valve replacement (TAVR) is insufficient. Frailty and serum albumin as a frailty marker were shown to correlate with prognosis after TAVR. We sought to evaluate the additive value of serum albumin to STS and EuroSCORE‐2 scores to predict mortality in individuals undergoing TAVR.

Design

Retrospective analysis.

Setting

Tertiary‐care hospital prospective registry.

Participants

Individuals who underwent TAVR (N = 426).

Measurements

We compared survival rates according to median baseline albumin levels (4 g/dL), STS score (4.5%), and EuroSCORE‐2 (3.45%). Participants were divided into four groups according to median serum albumin and median STS and EuroSCORE‐2 scores (high vs low), and 1‐year survival rates were compared. A category‐free net reclassification index (NRI) was calculated to compare the ability of a model of STS or EuroSCORE‐2 alone to classify mortality risk with and without the addition of baseline serum albumin.

Results

Participants with low albumin levels had higher mortality (hazard ratio (HR) = 3.03, 95% confidence interval (CI) = 1.66–5.26, P < .001). Participants with low serum albumin and a high STS (HR = 4.55, 95% CI = 2.21–9.38, P < .001) or EuroSCORE‐2 (HR = 2.72, 95% CI = 1.48–5.06, P = .001) score had higher mortality. Using NRI analysis, a model that included albumin in addition to STS correctly reclassified 42% of events (NRI = 0.58) and a model that included albumin in addition to EuroSCORE‐2 correctly reclassified 44% of events (NRI = 0.64).

Conclusion

Serum albumin, as a marker of frailty, can significantly improve the ability of STS and EuroSCORE‐2 scores to predict TAVR‐related mortality.
Evaluating student learning outcomes in oral health knowledge and skills
Authors: Lewis Adrienne , Edwards Suzanne , Whiting Glenda , Donnelly Frank
Published: September 2017

Aims and objectives

To evaluate whether a set of oral health resources designed for workforce training was relevant for students undertaking an entry‐level nursing or aged care qualification.

Background

Oral health is one of the most neglected aspects of nursing care experienced by older people. Despite efforts to improve aged care worker oral health knowledge and skills, one‐off training and rapid staff turnover have hindered the success of workplace programmes. Inadequate oral health content in entry‐level nursing and aged care qualifications has perpetuated this.

Design

Kirkpatrick's training and evaluation model was used to evaluate the resources developed by a project called Building Better Oral Health Communities. Students used them as prescribed study materials and completed pre‐ and postintervention questionnaires. Educators were interviewed to obtain their feedback. Quantitative data were analysed using descriptive and inferential statistics. Qualitative data were collated according to relevance to learning, presentation style and interest.

Results

Evaluation showed high levels of student and educator satisfaction. Student learning outcomes demonstrated consistently positive attitudes and significant self‐reported improvements in oral health knowledge and skills. Irrespective of course type, students gained similar levels of oral health knowledge and skills following use of the resources.

Conclusion

Nurses and care workers must be able to provide consistent standards of oral health care as a fundamental part of caring for patients. Validated as an effective learning and teaching package, it is recommended that these resources be used to strengthen the oral health content of entry‐level nursing and aged care qualifications.

Relevance to clinical practice

Building the oral health capacity of nurses and care workers is one way of reversing oral health neglect and improving the quality of care provided to older people.
Clinical Consequences of Hypertriglyceridemia‐Associated Proteinuria in Miniature Schnauzers
Authors: Smith R.E. , Granick J.L. , Stauthammer C.D. , Polzin D.J. , Heinrich D.A. , Furrow E.
Published: September 2017

Background

Primary hypertriglyceridemia is a common condition in older Miniature Schnauzers that recently has been associated with proteinuria and underlying glomerular pathology, particularly glomerular lipid thromboemboli. Consequences of glomerular disease can include hypertension, thromboembolic disease, and cardiac disease. The incidence of these sequelae in Miniature Schnauzers with hypertriglyceridemia‐associated proteinuria (HTGP) is unknown.

Objective

To investigate prevalence of hypertension, decreased antithrombinIIIactivity, and cardiac disease in Miniature Schnauzers with and withoutHTGP.

Animals

Thirty‐two Miniature Schnauzers ≥7 years old.

Methods

Prospective case‐control study. Data collected from dogs included aCBC, biochemistry panel, urinalysis, urine protein‐to‐creatinine ratio, urine cortisol‐to‐creatinine ratio, serum total thyroxine concentration, fasting serum triglyceride concentration, indirect blood pressure, antithrombinIIIactivity, and serum cardiac troponin I concentration. Results from dogs withHTGP(serum triglyceride concentration ≥ 100 mg/dLand urine protein‐to‐creatinine ratio >0.5) were statistically compared to normotriglyceridemic, nonproteinuric dogs.

Results

Eighteen of the 32 dogs (56%) had primary hypertriglyceridemia. Of those dogs, 8 of 18 had proteinuria. None of theHTGPdogs were azotemic or hypoalbuminemic. Serum albumin concentration, alkaline phosphatase activity, and cholesterol concentration were significantly increased in dogs withHGTPcompared to those withoutHGTP. No increased risk of hypertension, decreased antithrombinIIIactivity, or cardiac disease was noted. Limited data from 8 dogs withHTGPshowed no development of hypoalbuminemia or azotemia over a median follow‐up period of 18 months.

Conclusions and Clinical Importance

Geriatric Miniature Schnauzers withHGTPmay have a good prognosis overall, and are not typically azotemic or hypoalbuminemic.
Influence of Various Factors on Circulating 25(OH) Vitamin D Concentrations in Dogs with Cancer and Healthy Dogs
Authors: Weidner N. , Woods J.P. , Conlon P. , Meckling K.A. , Atkinson J.L. , Bayle J. , Makowski A.J. , Horst R.L. , Verbrugghe A.
Published: September 2017

Background

Low blood 25‐hydroxyvitamin D (25(OH)D) concentrations have been associated with cancer in dogs. Little research has examined what other factors may affect 25(OH)D concentrations.

Objectives

(1) To determine whether the presence of cancer (lymphoma, osteosarcoma, or mast cell tumor [MCT]) in dogs is associated with plasma 25(OH)D concentrations and (2) identify other factors related to plasma 25(OH)D concentrations in dogs.

Animals

Dogs newly diagnosed with osteosarcoma (n = 21), lymphoma (n = 27), and MCT (n = 21) presented to a tertiary referral oncology center, and healthy, client‐owned dogs (n = 23).

Methods

An observational study design was used. Dietary vitamin D intake, sex, age, body condition score (BCS), muscle condition score (MCS), and plasma concentrations of 25(OH)D, 24,25‐dihydroxyvitamin D (24,25(OH)2D) (a marker of CYP24A1 activity), as well as ionized calcium (ICa), parathyroid hormone, and parathyroid hormone‐related protein concentrations were measured. An analysis of covariance was used to model plasma 25(OH)D concentrations.

Results

Cancer type (P = 0.004), plasma 24,25(OH)2D concentrations (P < 0.001), and plasma ICa concentrations (P = 0.047) had significant effects on plasma 25(OH)D concentrations. Effects of age, sex, body weight, BCS, MCS, and plasma PTH concentrations were not identified. A significant interaction between ICa and cancer was found (P = 0.005). Plasma 25(OH)D concentrations increased as ICa concentrations increased in dogs with cancer, whereas plasma 25(OH)D concentrations decreased as ICa concentrations increased in healthy dogs.

Conclusions and Clinical Importance

Results support a relationship between cancer and altered vitamin D metabolism in dogs, mediated by plasma ICa concentrations. The CYP24A1 activity and plasma ICa should be measured in studies examining plasma 25(OH)D concentrations in dogs.
Mitogenic Activity of a Water‐Soluble Adjuvant (Bu‐WSA) Obtained from Bacterionema matruchotii
Authors: NITTA Toshimasa , OKUMURA Seiichi , TSUSHI Masao , NAKANO Masayasu
Published: September 2017

Butanol‐extracted water‐soluble adjuvant (Bu‐WSA) obtained from Bacterionema matruchotii was cultured with peripheral blood mononuclear cells (PBM) in the presence of sub‐ and/or supra‐optimal mitogenic concentrations of concanavalin A (Con A). The addition of Bu‐WSA resulted in increased tritiated thymidine incorporation above that produced by Con A alone. Bu‐WSA by itself is not mitogenic for PBM and in fact produced a decrease in thymidine uptake compared to the control. We investigated the response of subpopulation(s) of PBM to Bu‐WSA, Con A and a mixture of Bu‐WSA and Con A. Separation of PBM into purified T cells, B cells and macrophages showed that cell‐cell cooperation of T cells with B cells or macrophages is necessary for the observed synergistic effect of Bu‐WSA with Con A. A marked increase in thymidine incorporation by the mixture of T and B cell populations occurred, while only a small amount of thymidine was incorporated when the B cell population was absent. Mitomycin treatment revealed that the response could be ascribed to the T‐cell response with a B‐cell helper effect. Moreover, Con A and Bu‐WSA appeared to act on the same T cell population. This model may provide unique information about the activation of human peripheral blood T cells compared with the activation of these cells by other mitogens.
Absence of the KhpA and KhpB (JAG/EloR) RNA‐binding proteins suppresses the requirement for PBP2b by overproduction of FtsA in Streptococcus pneumoniae D39
Authors: Zheng Jiaqi J. , Perez Amilcar J. , Tsui Ho‐Ching Tiffany , Massidda Orietta , Winkler Malcolm E.
Published: September 2017

Suppressor mutations were isolated that obviate the requirement for essential PBP2b in peripheral elongation of peptidoglycan from the midcells of dividing Streptococcus pneumoniae D39 background cells. One suppressor was in a gene encoding a single KH‐domain protein (KhpA). ΔkhpA suppresses deletions in most, but not all (mltG), genes involved in peripheral PG synthesis and in the gpsB regulatory gene. ΔkhpA mutations reduce growth rate, decrease cell size, minimally affect shape and induce expression of the WalRK cell‐wall stress regulon. Reciprocal co‐immunoprecipitations show that KhpA forms a complex in cells with another KH‐domain protein (KhpB/JAG/EloR). ΔkhpA and ΔkhpB mutants phenocopy each other exactly, consistent with a direct interaction. RNA‐immunoprecipitation showed that KhpA/KhpB bind an overlapping set of RNAs in cells. Phosphorylation of KhpB reported previously does not affect KhpB function in the D39 progenitor background. A chromosome duplication implicated FtsA overproduction in Δpbp2b suppression. We show that cellular FtsA concentration is negatively regulated by KhpA/B at the post‐transcriptional level and that FtsA overproduction is necessary and sufficient for suppression of Δpbp2b. However, increased FtsA only partially accounts for the phenotypes of ΔkhpA mutants. Together, these results suggest that multimeric KhpA/B may function as a pleiotropic RNA chaperone controlling pneumococcal cell division.
Successful Control of Pain from Malignant Psoas Syndrome by Spinal Opioid with Local Anesthetic Agents
Authors: Yamaguchi Takashi , Katayama Katsuyuki , Matsumoto Mina , Sato Yoshifumi , Nakayama Noriko , Hisahara Ko
Published: September 2017

Background

Malignant psoas syndrome (MPS) is a rare but distressing pain syndrome observed in advanced cancer patients. Pain due to MPS is often refractory to multimodal analgesic treatment, including opioid analgesics. As only 1 case demonstrating the efficacy of neuraxial analgesia in managing pain due to MPS has been reported, its role in MPS remains uncertain.

Cases

We present 3 cases demonstrating the successful management of pain due to MPS using spinal opioids with local anesthetic agents. All patients were under the care of the palliative care consultation service in an acute care hospital and refractory to multimodal analgesic treatment, including opioid, non‐opioid, and adjuvant analgesics. Switching opioid administration to the epidural or intrathecal route with a local anesthetic agent provided good pain control in all 3 patients. Moreover, all patients showed improvements in both Palliative Performance Scale and Functional Independence Measure scores after starting a spinal opioid with a local anesthetic agent.

Conclusions

The findings in the present cases indicate neuraxial analgesia may be of benefit, in terms of managing pain and improving functional status, in MPS patients with insufficient pain control by multimodal analgesic treatment. Physicians should consider the use of neuraxial analgesia in cases of MPS where pain is uncontrolled with multimodal analgesic treatment to provide the best possible quality of life for patients with MPS.
Host‐induced silencing of essential genes in Puccinia triticina through transgenic expression of RNAi sequences reduces severity of leaf rust infection in wheat
Authors: Panwar Vinay , Jordan Mark , McCallum Brent , Bakkeren Guus
Published: September 2017

Leaf rust, caused by the pathogenic fungus Puccinia triticina (Pt), is one of the most serious biotic threats to sustainable wheat production worldwide. This obligate biotrophic pathogen is prevalent worldwide and is known for rapid adaptive evolution to overcome resistant wheat varieties. Novel disease control approaches are therefore required to minimize the yield losses caused by Pt. Having shown previously the potential of host‐delivered RNA interference (HD‐RNAi) in functional screening of Pt genes involved in pathogenesis, we here evaluated the use of this technology in transgenic wheat plants as a method to achieve protection against wheat leaf rust (WLR) infection. Stable expression of hairpin RNAi constructs with sequence homology to Pt MAP‐kinase (PtMAPK1) or a cyclophilin (PtCYC1) encoding gene in susceptible wheat plants showed efficient silencing of the corresponding genes in the interacting fungus resulting in disease resistance throughout the T2 generation. Inhibition of Pt proliferation in transgenic lines by in planta‐induced RNAi was associated with significant reduction in target fungal transcript abundance and reduced fungal biomass accumulation in highly resistant plants. Disease protection was correlated with the presence of siRNA molecules specific to targeted fungal genes in the transgenic lines harbouring the complementary HD‐RNAi construct. This work demonstrates that generating transgenic wheat plants expressing RNAi‐inducing transgenes to silence essential genes in rust fungi can provide effective disease resistance, thus opening an alternative way for developing rust‐resistant crops.
Effect of parental RNA interference of a transformer‐2 homologue on female reproduction and offspring sex determination in Asian citrus psyllid
Authors: Yu Xiudao , Killiny Nabil
Published: September 2017

Asian citrus psyllid Diaphorina citri Kuwayama is the vector of Candidatus Liberibacter asiaticus (CLas), the causal agent of citrus huanglongbing (HLB). A comprehensive understanding of molecular components that govern key physiological traits in D. citri would promote the development of novel genetic control strategies to fight this pest. In the present study, a transformer 2 homologue (Dctra‐2) implicated in embryonic sex differentiation in dipteran insects is targeted to interfere with the offspring sex ratio of D. citri. The results of the present study show that Dctra‐2 is constitutively expressed at all developmental stages and in both females and males during the adult stage. Quantitative reverse transcriptase‐polymerase chain reaction analysis confirms the double‐stranded RNA‐mediated RNA interference (RNAi) of the Dctra‐2. RNAi effects in D. citri female adults can be transferred in a trans‐generational manner to their eggs and progeny, which are commonly referred as parental RNAi. RNAi females lay fewer eggs, with a mean of 12.44, and the hatching rate of laid eggs is reduced approximately by 29.86% compared with the control. However, parental RNAi of Dctra‐2 do not produce male‐biased progeny. The results suggest that Dctra‐2 is an effective RNAi target for use in the management of D. citri. In addition, the parental RNAi would provide an effective tool for studying the function of early embryonic genes in D. citri.
Ontogeny of protein concentration, haemocyte concentration and antimicrobial activity against Escherichia coli in haemolymph of the invasive harlequin ladybird Harmonia axyridis (Coleoptera: Coccinellidae)
Authors: Řeřicha Michal , Dobeš Pavel , Hyršl Pavel , Knapp Michal
Published: September 2017

The harlequin ladybird is considered to be one of the most successful invasive insect species. Among other traits, its invasive success is considered to be caused by a powerful immune system. In the present study, we investigate the ontogenetic profile of protein concentration, concentration of circulating haemocytes and constitutive antimicrobial activity against Escherichia coli in Harmonia axyridis haemolymph during late larval development and early adult life. Protein concentration increases during the first 32 days of adult life from 45 to 100 mg per mL of haemolymph and reaches intermediate values during larval stages. The concentration of circulating haemocytes is very low (5000 haemocytes per μL of haemolymph) in late larval stages and increases strongly during first 8 days of adult life to values of approximately 30 000 haemocytes per μL of haemolymph. The killing efficiency of haemolymph against E. coli is lowest in larval stages, rapidly increases in the prepupal stage and then steadily grows during the whole period of adult life. There are no significant effects of sex on any of the investigated physiological or immune parameters. In general, the patterns observed for H. axyridis contrast with many results that are reported for other insects (e.g. bees, fruit flies, crickets or mosquitoes). One possible explanation is the contrasting life history of H. axyridis, with a fast preimaginal development and a long adult lifespan being linked to a long reproductive period. Substantial variation in physiological and immune parameters during ontogeny also has important methodological implications because individuals of exactly the same stage/age have to be employed for comparative studies.
Non‐invasive ventilation during cycle exercise training in patients with chronic respiratory failure on long‐term ventilatory support: A randomized controlled trial
Authors: Vitacca Michele , Kaymaz Dicle , Lanini Barbara , Vagheggini Guido , Ergün Pınar , Gigliotti Francesco , Ambrosino Nicolino , Paneroni Mara
Published: September 2017

ABSTRACT

Background and objective

The role of non‐invasive ventilation (NIV) during exercise training (ET) in patients with chronic respiratory failure (CRF) is still unclear. The aim of this study was to test whether NIV during ET had an additional effect in increasing the 6‐min walking distance (6MWD) and cycle endurance time compared with ET alone.

Methods

All patients underwent 20 sessions of cycle training over 3 weeks and were randomly assigned to ET with NIV or ET alone. Outcome measures were 6MWD (primary outcome), incremental and endurance cycle ergometer exercise time, respiratory muscle function, quality of life by the Maugeri Respiratory Failure questionnaire (MRF‐28), dyspnoea (Medical Research Council scale) and leg fatigue at rest.

Results

Forty‐two patients completed the study. Following training, no significant difference in 6MWD changes were found between groups. Improvement in endurance time was significantly greater in the NIV group compared with the non‐NIV training group (754 ± 973 vs 51 ± 406 s, P = 0.0271); dyspnoea improved in both groups, while respiratory muscle function and leg fatigue improved only in the NIV ET group. MRF‐28 improved only in the group training without NIV.

Conclusion

In CRF patients on long‐term NIV and long‐term oxygen therapy (LTOT), the addition of NIV to ET sessions resulted in an improvement in endurance time, but not in 6MWD.
Sparse Graphs Using Exchangeable Random Measures
Authors: Caron François , Fox Emily B.
Published: September 2017

Statistical network modelling has focused on representing the graph as a discrete structure, namely the adjacency matrix. When assuming exchangeability of this array—which can aid in modelling, computations and theoretical analysis—the Aldous–Hoover theorem informs us that the graph is necessarily either dense or empty. We instead consider representing the graph as an exchangeable random measure and appeal to the Kallenberg representation theorem for this object. We explore using completely random measures (CRMs) to define the exchangeable random measure, and we show how our CRM construction enables us to achieve sparse graphs while maintaining the attractive properties of exchangeability. We relate the sparsity of the graph to the Lévy measure defining the CRM. For a specific choice of CRM, our graphs can be tuned from dense to sparse on the basis of a single parameter. We present a scalable Hamiltonian Monte Carlo algorithm for posterior inference, which we use to analyse network properties in a range of real data sets, including networks with hundreds of thousands of nodes and millions of edges.
Dysregulation of Circulating Tfr/Tfh Ratio in Primary biliary cholangitis
Authors: Zheng J. , Wang T. , Zhang L. , Cui L.
Published: September 2017

Follicular helper T (Tfh) cells and follicular regulatory T (Tfr) cells are critical for the development and maintenance of germinal centre (GC) and humoral immune responses. Accumulating evidence has demonstrated that the dysregulation of either Tfh cells or Tfr cells contributes to the pathogenesis of autoimmune diseases. We aim to investigate the roles of circulating Tfh cells and circulating Tfr cells in the pathogenesis of primary biliary cholangitis (PBC). A total of 34 patients with PBC and 27 health individuals were enrolled in this study. Flow cytometry revealed that circulating Tfh (CD4+CXCR5+CD127hiCD25lo) cells were increased, but Tfr (CD4+CXCR5+CD127loCD25hi) cells and ratio of Tfr/Tfh were dramatically decreased in PBC patients compared with healthy controls. The Tfr/Tfh ratio was negatively correlated with level of serum IgM. Meanwhile, we also observed effector memory (CCR7loPD‐1hi) Tfh cells and Tfr cells were dramatically increased, but central memory (CCR7hiPD‐1lo) Tfh cells and Tfr cells were decreased in PBC patients compared with healthy controls. Effector memory Tfr cells were positively correlated with level of serum ALP. These results indicate that an imbalance of circulating Tfr cells and Tfh cells may be involved in the immunopathogenesis of PBC and may provide novel insight for the development of PBC therapies.
Two novel alleles, HLA‐A*02:643N and HLA‐B*53:44, identified in Brazilian individuals
Authors: Vale E. M. G. , Nascimento E. , Oliveira C. K. F. , Lasmar M. F. , Fabreti‐Oliveira R. A.
Published: September 2017

Two novel alleles, HLA‐A*02:643N and HLA‐B*53:44, generated by different mechanisms, were identified in Brazilian individuals.
NbEXPA1, an α‐expansin, is plasmodesmata‐specific and a novel host factor for potyviral infection
Authors: Park Sang‐Ho , Li Fangfang , Renaud Justin , Shen Wentao , Li Yinzi , Guo Lihua , Cui Hongguang , Sumarah Mark , Wang Aiming
Published: September 2017

Plasmodesmata (PD), unique to the plant kingdom, are structurally complex microchannels that cross the cell wall to establish symplastic communication between neighbouring cells. Viral intercellular movement occurs through PD. To better understand the involvement of PD in viral infection, we conducted a quantitative proteomic study on the PD‐enriched fraction from Nicotiana benthamiana leaves in response to infection by Turnip mosaic virus (TuMV). We report the identification of a total of 1070 PD protein candidates, of which 100 (≥2‐fold increase) and 48 (≥2‐fold reduction) are significantly differentially accumulated in the PD‐enriched fraction, when compared with protein levels in the corresponding healthy control. Among the differentially accumulated PD protein candidates, we show that an α‐expansin designated NbEXPA1, a cell wall loosening protein, is PD‐specific. TuMV infection downregulates NbEXPA1 mRNA expression and protein accumulation. We further demonstrate that NbEXPA1 is recruited to the viral replication complex via the interaction with NIb, the only RNA‐dependent RNA polymerase of TuMV. Silencing of NbEXPA1 inhibits plant growth and TuMV infection, whereas overexpression of NbEXPA1 promotes viral replication and intercellular movement. These data suggest that NbEXPA1 is a host factor for potyviral infection. This study not only generates a PD‐proteome dataset that is useful in future studies to expound PD biology and PD‐mediated virus–host interactions but also characterizes NbEXPA1 as the first PD‐specific cell wall loosening protein and its essential role in potyviral infection.
CDK5‐dependent activation of dynein in the axon initial segment regulates polarized cargo transport in neurons
Authors: Klinman Eva , Tokito Mariko , Holzbaur Erika L. F.
Published: September 2017

The unique polarization of neurons depends on selective sorting of axonal and somatodendritic cargos to their correct compartments. Axodendritic sorting and filtering occurs within the axon initial segment (AIS). However, the underlying molecular mechanisms responsible for this filter are not well understood. Here, we show that local activation of the neuronal‐specific kinase cyclin‐dependent kinase 5 (CDK5) is required to maintain AIS integrity, as depletion or inhibition of CDK5 induces disordered microtubule polarity and loss of AIS cytoskeletal structure. Furthermore, CDK5‐dependent phosphorylation of the dynein regulator Ndel1 is required for proper re‐routing of mislocalized somatodendritic cargo out of the AIS; inhibition of this pathway induces profound mis‐sorting defects. While inhibition of the CDK5‐Ndel1‐Lis1‐dynein pathway alters both axonal microtubule polarity and axodendritic sorting, we found that these defects occur on distinct timescales; brief inhibition of dynein disrupts axonal cargo sorting before loss of microtubule polarity becomes evident. Together, these studies identify CDK5 as a master upstream regulator of trafficking in vertebrate neurons, required for both AIS microtubule organization and polarized dynein‐dependent sorting of axodendritic cargos, and support an ongoing and essential role for dynein at the AIS.
N‐glycolylneuraminic acid knockout reduces erythrocyte sequestration and thromboxane elaboration in an ex vivo pig‐to‐human xenoperfusion model
Authors: Cimeno Arielle , Hassanein Wessam , French Beth M. , Powell Jessica M. , Burdorf Lars , Goloubeva Olga , Cheng Xiangfei , Parsell Dawn M. , Ramsoondar Jagdeece , Kuravi Kasinath , Vaught Todd , Uluer Mehmet C. , Redding Emily , O'Neill Natalie , Laird Christopher , Hershfeld Alena , Tatarov Ivan , Thomas Kathryn , Ayares David , Azimzadeh Agnes M. , Pierson Richard N. , Barth Rolf N. , LaMattina John C.
Published: September 2017

Background

Wild‐type pigs express several carbohydrate moieties on their cell surfaces that differ from those expressed by humans. This difference in profile leads to pig tissue cell recognition of human blood cells causing sequestration, in addition to antibody‐mediated xenograft injury. One such carbohydrate is N‐glycolylneuraminic acid (Neu5Gc), a sialic acid molecule synthesized in pigs but not in humans. Here, we evaluate livers with and without Neu5Gc in an ex vivo liver xeno perfusion model.

Methods

Livers from pigs with an α1,3‐galactosyl transferase gene knockout (GalTKO) and transgenic for human membrane cofactor (hCD46) with (n = 5) or without (n = 7) an additional Neu5Gc gene knock out (Neu5GcKO) were perfused ex vivo with heparinized whole human blood. A drug regimen consisting of a histamine inhibitor, thromboxane synthase inhibitor, and a murine anti‐human GPIb‐blocking antibody fragment was given to half of the experiments in each group.

Results

Liver function tests (AST and ALT) were not significantly different between livers with and without the Neu5GcKO. GalTKO.hCD46.Neu5GcKO livers had less erythrocyte sequestration as evidenced by a higher mean hematocrit over time compared to GalTKO.hCD46 livers (P = .0003). The addition of Neu5GcKO did not ameliorate profound thrombocytopenia seen within the first 15 minutes of perfusion. TXB2 was significantly less with the added drug regimen (P = .006) or the presence of Neu5GcKO (P = .017).

Conclusions

The lack of Neu5Gc expression attenuated erythrocyte loss but did not prevent profound early onset thrombocytopenia or platelet activation, although TXB2 levels were decreased in the presence of Neu5GcKO.
Congenital aortic valve repair using CorMatrix®: A histologic evaluation
Authors: Hofmann Michael , Schmiady Martin O. , Burkhardt Barbara E. , Dave Hitendu H. , Hübler Michael , Kretschmar Oliver , Bode Peter K.
Published: September 2017

Background

The reconstruction of heart valves provides substantial benefits, particularly in the pediatric population. We present our experience using decellularized extracellular matrix (dECM, CorMatrix®) for aortic valve procedures.

Methods

We retrospectively reviewed the case histories of 6 patients (aged from 2 months ‐ 14 years) who underwent surgery for severe aortic valve stenosis (n = 4) or regurgitation (n = 2). Aortic valve repair was performed on all patients using dECM as a leaflet replacement or leaflet extension. Follow‐ups were performed using echocardiography. Reoperation was necessary in 4 cases, and the dECM was explanted and examined histologically and immunohistochemically.

Results

The early post‐operative period was uneventful, and the scaffold fulfilled the mechanical requirements. Significant valve insufficiency developed in 5 patients during the post‐operative period (119‐441 days postoperatively). In all specimens, only a migration of inflammatory cells was identified, which induced structural and functional changes caused by the chronic inflammatory response.

Conclusions

Our results suggest a mixed immunological response of remodeling and inflammation following the implantation. The expected process of seeding/migration and remodeling of the bioscaffold into the typical 3‐layered architecture were not observed in our explanted specimens.
Cycling Through Cancer: Exploring Childhood Cancer Survivors’ Experiences of Well- and Ill-Being
Authors: Burke Shaunna M. , Brunet Jennifer , Wurz Amanda , Butler Christina , Utley Andrea
Published: September 2017

The benefits of informal physical activity during recovery from childhood cancer have rarely been investigated. This study adopted a multiple case study approach to explore the impact of recreational cycling on childhood cancer survivors’ experiences of well- and ill-being. Three semistructured interviews were conducted over a 3-month period with four survivors to explore their experiences of physical, psychological, and social well- and ill-being. Within-case analysis followed by cross-case analysis identified three themes that captured their well- and ill-being experiences with recreational cycling and cancer: (a) cultivating feelings and emotions, (b) experiencing physical changes, and (c) encountering positive and negative social interactions. The results from this study show that recreational cycling may be a useful adjunct to conventional treatments for the self-management of multiple domains of well- and ill-being during recovery from childhood cancer.
Superadditivity of two quantum information resources
Authors: Nawareg Mohamed , Muhammad Sadiq , Horodecki Pawel , Bourennane Mohamed
Published: September 2017

Demonstration of the superadditivity of two quantum information resources with three-partite nondistillable entangled states.
New models for energy beam machining enable accurate generation of free forms
Authors: Axinte Dragos , Billingham John , Bilbao Guillerna Aitor
Published: September 2017

A generic mathematical model determines the beam paths for various energy beam machining processes to generate free-form surfaces.
A variational approach to probing extreme events in turbulent dynamical systems
Authors: Farazmand Mohammad , Sapsis Themistoklis P.
Published: September 2017

A variational framework for the analysis and data-driven prediction of extreme events is developed.
A predictive framework for the design and fabrication of icephobic polymers
Authors: Golovin Kevin , Tuteja Anish
Published: September 2017

Here, we show how to predictably impart extremely low ice adhesion to a range of different plastic materials.
Skin infections are eliminated by cooperation of the fibrinolytic and innate immune systems
Authors: Santus William , Barresi Simona , Mingozzi Francesca , Broggi Achille , Orlandi Ivan , Stamerra Giulia , Vai Marina , Martorana Alessandra M. , Polissi Alessandra , Köhler Julia R. , Liu Ningning , Zanoni Ivan , Granucci Francesca
Published: September 2017

A balanced TGF-β–mediated fibrotic response drives the control and elimination of fungal and bacterial skin infections.
A Novel Aerobic Degradation Pathway for Thiobencarb Is Initiated by the TmoAB Two-Component Flavin Mononucleotide-Dependent Monooxygenase System in Acidovorax sp. Strain T1
Authors: Chu Cui-Wei , Liu Bin , Li Na , Yao Shi-Gang , Cheng Dan , Zhao Jia-Dong , Qiu Ji-Guo , Yan Xin , He Qin , He Jian
Published: September 2017

Thiobencarb is a thiocarbamate herbicide used in rice paddies worldwide. Microbial degradation plays a crucial role in the dissipation of thiobencarb in the environment. However, the physiological and genetic mechanisms underlying thiobencarb degradation remain unknown. In this study, a novel thiobencarb degradation pathway was proposed in
Acidovorax
sp. strain T1. Thiobencarb was oxidized and cleaved at the C—S bond, generating diethylcarbamothioic
S
-acid and 4-chlorobenzaldehyde (4CDA). 4CDA was then oxidized to 4-chlorobenzoic acid (4CBA) and hydrolytically dechlorinated to 4-hydroxybenzoic acid (4HBA). The identification of catabolic genes suggested further hydroxylation to protocatechuic acid (PCA) and finally degradation through the protocatechuate 4,5-dioxygenase pathway. A novel two-component monooxygenase system identified in the strain, TmoAB, was responsible for the initial catabolic reaction. TmoA shared 28 to 32% identity with the oxygenase components of pyrimidine monooxygenase from
Agrobacterium fabrum
, alkanesulfonate monooxygenase from
Pseudomonas savastanoi
, and dibenzothiophene monooxygenase from
Rhodococcus
sp. TmoB shared 25 to 37% identity with reported flavin reductases and oxidized NADH but not NADPH. TmoAB is a flavin mononucleotide (FMN)-dependent monooxygenase and catalyzed the C—S bond cleavage of thiobencarb. Introduction of
tmoAB
into cells of the thiobencarb degradation-deficient mutant T1m restored its ability to degrade and utilize thiobencarb. A dehydrogenase gene,
tmoC
, was located 7,129 bp downstream of
tmoAB
, and its transcription was clearly induced by thiobencarb. The purified TmoC catalyzed the dehydrogenation of 4CDA to 4CBA using NAD
+
as a cofactor. A gene cluster responsible for the complete 4CBA metabolic pathway was also cloned, and its involvement in thiobencarb degradation was preliminarily verified by transcriptional analysis.

IMPORTANCE
Microbial degradation is the main factor in thiobencarb dissipation in soil. In previous studies, thiobencarb was degraded initially via
N
-deethylation, sulfoxidation, hydroxylation, and dechlorination. However, enzymes and genes involved in the microbial degradation of thiobencarb have not been studied. This study revealed a new thiobencarb degradation pathway in
Acidovorax
sp. strain T1 and identified a novel two-component FMN-dependent monooxygenase system, TmoAB. Under TmoAB-mediated catalysis, thiobencarb was cleaved at the C—S bond, producing diethylcarbamothioic
S
-acid and 4CDA. Furthermore, the downstream degradation pathway of thiobencarb was proposed. Our study provides the physiological, biochemical, and genetic foundation of thiobencarb degradation in this microorganism.
Coadministration of the Campylobacter jejuni N-Glycan-Based Vaccine with Probiotics Improves Vaccine Performance in Broiler Chickens
Authors: Nothaft H. , Perez-Muñoz M. E. , Gouveia G. J. , Duar R. M. , Wanford J. J. , Lango-Scholey L. , Panagos C. G. , Srithayakumar V. , Plastow G. S. , Coros C. , Bayliss C. D. , Edison A. S. , Walter J. , Szymanski C. M.
Published: September 2017

Source attribution studies report that the consumption of contaminated poultry is the primary source for acquiring human campylobacteriosis. Oral administration of an engineered
Escherichia coli
strain expressing the
Campylobacter jejuni
N-glycan reduces bacterial colonization in specific-pathogen-free leghorn chickens, but only a fraction of birds respond to vaccination. Optimization of the vaccine for commercial broiler chickens has great potential to prevent the entry of the pathogen into the food chain. Here, we tested the same vaccination approach in broiler chickens and observed similar efficacies in pathogen load reduction, stimulation of the host IgY response, the lack of
C. jejuni
resistance development, uniformity in microbial gut composition, and the bimodal response to treatment. Gut microbiota analysis of leghorn and broiler vaccine responders identified one member of
Clostridiales
cluster XIVa,
Anaerosporobacter mobilis
, that was significantly more abundant in responder birds. In broiler chickens, coadministration of the live vaccine with
A. mobilis
or
Lactobacillus reuteri
, a commonly used probiotic, resulted in increased vaccine efficacy, antibody responses, and weight gain. To investigate whether the responder-nonresponder effect was due to the selection of a
C. jejuni
“supercolonizer mutant” with altered phase-variable genes, we analyzed all poly(G)-containing loci of the input strain compared to nonresponder colony isolates and found no evidence of phase state selection. However, untargeted nuclear magnetic resonance (NMR)-based metabolomics identified a potential biomarker negatively correlated with
C. jejuni
colonization levels that is possibly linked to increased microbial diversity in this subgroup. The comprehensive methods used to examine the bimodality of the vaccine response provide several opportunities to improve the
C. jejuni
vaccine and the efficacy of any vaccination strategy.

IMPORTANCE
Campylobacter jejuni
is a common cause of human diarrheal disease worldwide and is listed by the World Health Organization as a high-priority pathogen.
C. jejuni
infection typically occurs through the ingestion of contaminated chicken meat, so many efforts are targeted at reducing
C. jejuni
levels at the source. We previously developed a vaccine that reduces
C. jejuni
levels in egg-laying chickens. In this study, we improved vaccine performance in meat birds by supplementing the vaccine with probiotics. In addition, we demonstrated that
C. jejuni
colonization levels in chickens are negatively correlated with the abundance of clostridia, another group of common gut microbes. We describe new methods for vaccine optimization that will assist in improving the
C. jejuni
vaccine and other vaccines under development.
Genetic Diversity of Infectious Laryngotracheitis Virus duringIn VivoCoinfection Parallels Viral Replication and Arises from Recombination Hot Spots within the Genome
Authors: Loncoman Carlos A. , Hartley Carol A. , Coppo Mauricio J. C. , Vaz Paola K. , Diaz-Méndez Andrés , Browning Glenn F. , García Maricarmen , Spatz Stephen , Devlin Joanne M.
Published: September 2017

Recombination is a feature of many alphaherpesviruses that infect people and animals. Infectious laryngotracheitis virus (ILTV;Gallid alphaherpesvirus 1) causes respiratory disease in chickens, resulting in significant production losses in poultry industries worldwide. Natural (field) ILTV recombination is widespread, particularly recombination between attenuated ILTV vaccine strains to create virulent viruses. These virulent recombinants have had a major impact on animal health. Recently, the development of a single nucleotide polymorphism (SNP) genotyping assay for ILTV has helped to understand ILTV recombination in laboratory settings. In this study, we applied this SNP genotyping assay to further examine ILTV recombination in the natural host. Following coinoculation of specific-pathogen-free chickens, we examined the resultant progeny for evidence of viral recombination and characterized the diversity of the recombinants over time. The results showed that ILTV replication and recombination are closely related and that the recombinant viral progeny are most diverse 4 days after coinoculation, which is the peak of viral replication. Further, the locations of recombination breakpoints in a selection of the recombinant progeny, and in field isolates of ILTV from different geographical regions, were examined following full-genome sequencing and used to identify recombination hot spots in the ILTV genome.

IMPORTANCEAlphaherpesviruses are common causes of disease in people and animals. Recombination enables genome diversification in many different species of alphaherpesviruses, which can lead to the evolution of higher levels of viral virulence. Using the alphaherpesvirus infectious laryngotracheitis virus (ILTV), we performed coinfections in the natural host (chickens) to demonstrate high levels of virus recombination. Higher levels of diversity in the recombinant progeny coincided with the highest levels of virus replication. In the recombinant progeny, and in field isolates, recombination occurred at greater frequency in recombination hot spot regions of the virus genome. Our results suggest that control measures that aim to limit viral replication could offer the potential to limit virus recombination and thus the evolution of virulence. The development and use of vaccines that are focused on limiting virus replication, rather than vaccines that are focused more on limiting clinical disease, may be indicated in order to better control disease.
A Distinctive and Host-Restricted Gut Microbiota in Populations of a Cactophilic Drosophila Species
Authors: Martinson Vincent G. , Carpinteyro-Ponce Javier , Moran Nancy A. , Markow Therese A.
Published: September 2017

Almost all animals possess gut microbial communities, but the nature of these communities varies immensely. For example, in social bees and mammals, the composition is relatively constant within species and is dominated by specialist bacteria that do not live elsewhere; in laboratory studies and field surveys of
Drosophila melanogaster
, however, gut communities consist of bacteria that are ingested with food and that vary widely among individuals and localities. We addressed whether an ecological specialist in its natural habitat has a microbiota dominated by gut specialists or by environmental bacteria.
Drosophila nigrospiracula
is a species that is endemic to the Sonoran Desert and is restricted to decaying tissues of two giant columnar cacti,
Pachycereus pringlei
(cardón cactus) and
Carnegiea gigantea
(saguaro cactus). We found that the
D. nigrospiracula
microbiota differs strikingly from that of the cactus tissue on which the flies feed. The most abundant bacteria in the flies are rare or completely absent in the cactus tissue and are consistently abundant in flies from different cacti and localities. Several of these fly-associated bacterial groups, such as the bacterial order
Orbales
and the genera
Serpens
and
Dysgonomonas
, have been identified in prior surveys of insects from the orders Hymenoptera, Coleoptera, Lepidoptera, and Diptera, including several
Drosophila
species. Although the functions of these bacterial groups are mostly unexplored,
Orbales
species studied in bees are known to break down plant polysaccharides and use the resulting sugars. Thus, these bacterial groups appear to be specialized to the insect gut environment, where they may colonize through direct host-to-host transmission in natural settings.

IMPORTANCE
Flies in the genus
Drosophila
have become laboratory models for microbiota research, yet the bacteria commonly used in these experiments are rarely found in wild-caught flies and instead represent bacteria also present in the food. This study shows that an ecologically specialized
Drosophila
species possesses a distinctive microbiome, composed of bacterial types absent from the flies' natural food but widespread in other wild-caught insects. This study highlights the importance of fieldwork-informed microbiota research.