bluuebunny/crossref_metadata_2025 huggingface dataset:
Kinase-independent function of E-type cyclins in liver cancer
Authors: Geng Yan , Michowski Wojciech , Chick Joel M. , Wang Yaoyu E. , Jecrois M. Emmanuelle , Sweeney Katharine E. , Liu Lijun , Han Richard C. , Ke Nan , Zagozdzon Agnieszka , Sicinska Ewa , Bronson Roderick T. , Gygi Steven P. , Sicinski Piotr
Published: January 2018

Significance

Amplification of the cyclin E genes and overexpression of cyclin E proteins is very frequent in several human tumor types. In particular, overexpression of E cyclins was implicated in the pathogenesis of liver cancers. According to the current cell division models, E cyclins drive tumor cell proliferation by activating its kinase partner, the cyclin-dependent kinase 2 (CDK2). In this study, we demonstrate that E cyclins are dispensable for adult mouse physiology, but essential for liver cancer progression. Surprisingly, we found that the function of E cyclins in liver tumorigenesis is kinase independent. Our study suggests that agents targeting E cyclins would be efficacious in liver cancer treatment, as they would halt proliferation of tumor cells while sparing normal tissues.
Emergent chirality in the electric polarization texture of titanate superlattices
Authors: Shafer Padraic , García-Fernández Pablo , Aguado-Puente Pablo , Damodaran Anoop R. , Yadav Ajay K. , Nelson Christopher T. , Hsu Shang-Lin , Wojdeł Jacek C. , Íñiguez Jorge , Martin Lane W. , Arenholz Elke , Junquera Javier , Ramesh Ramamoorthy
Published: January 2018

Significance

Many natural structures exhibit chirality that is essential to their functional interactions, yet the chiral electronic structures found in condensed matter systems have been primarily limited to magnetic materials. Notably, the electric dipole equivalent of magnetic skyrmions has remained conspicuously elusive. However, recent theoretical predictions and experimental observations of the continuous rotation of electric polarization in titanate superlattices suggests that such complex oxide nanocomposites are ideal candidates for realizing chiral electric dipole configurations. Here we present the results from superlattices of PbTiO
3
and SrTiO
3
using a combination of resonant soft X-ray diffraction and second-principles simulations. We observe chiral arrays of polar line defects, spontaneously formed by the complex interactions in these artificial superlattices constructed from two nonchiral lattices.
Iterative optimization yields Mcl-1–targeting stapled peptides with selective cytotoxicity to Mcl-1–dependent cancer cells
Authors: Rezaei Araghi Raheleh , Bird Gregory H. , Ryan Jeremy A. , Jenson Justin M. , Godes Marina , Pritz Jonathan R. , Grant Robert A. , Letai Anthony , Walensky Loren D. , Keating Amy E.
Published: January 2018

Bcl-2 family proteins regulate apoptosis, and aberrant interactions of overexpressed antiapoptotic family members such as Mcl-1 promote cell transformation, cancer survival, and resistance to chemotherapy. Discovering potent and selective Mcl-1 inhibitors that can relieve apoptotic blockades is thus a high priority for cancer research. An attractive strategy for disabling Mcl-1 involves using designer peptides to competitively engage its binding groove, mimicking the structural mechanism of action of native sensitizer BH3-only proteins. We transformed Mcl-1–binding peptides into α-helical, cell-penetrating constructs that are selectively cytotoxic to Mcl-1–dependent cancer cells. Critical to the design of effective inhibitors was our introduction of an all-hydrocarbon cross-link or “staple” that stabilizes α-helical structure, increases target binding affinity, and independently confers binding specificity for Mcl-1 over related Bcl-2 family paralogs. Two crystal structures of complexes at 1.4 Å and 1.9 Å resolution demonstrate how the hydrophobic staple induces an unanticipated structural rearrangement in Mcl-1 upon binding. Systematic sampling of staple location and iterative optimization of peptide sequence in accordance with established design principles provided peptides that target intracellular Mcl-1. This work provides proof of concept for the development of potent, selective, and cell-permeable stapled peptides for therapeutic targeting of Mcl-1 in cancer, applying a design and validation workflow applicable to a host of challenging biomedical targets.
Protein aggregation of the p63 transcription factor underlies severe skin fragility in AEC syndrome
Authors: Russo Claudia , Osterburg Christian , Sirico Anna , Antonini Dario , Ambrosio Raffaele , Würz Julia Maren , Rinnenthal Jörg , Ferniani Marco , Kehrloesser Sebastian , Schäfer Birgit , Güntert Peter , Sinha Satrajit , Dötsch Volker , Missero Caterina
Published: January 2018

The
p63
gene encodes a master regulator of epidermal commitment, development, and differentiation. Heterozygous mutations in the C-terminal domain of the
p63
gene can cause ankyloblepharon-ectodermal defects-cleft lip/palate (AEC) syndrome, a life-threatening disorder characterized by skin fragility and severe, long-lasting skin erosions. Despite deep knowledge of p63 functions, little is known about mechanisms underlying disease pathology and possible treatments. Here, we show that multiple AEC-associated p63 mutations, but not those causative of other diseases, lead to thermodynamic protein destabilization, misfolding, and aggregation, similar to the known p53 gain-of-function mutants found in cancer. AEC mutant proteins exhibit impaired DNA binding and transcriptional activity, leading to dominant negative effects due to coaggregation with wild-type p63 and p73. Importantly, p63 aggregation occurs also in a conditional knock-in mouse model for the disorder, in which the misfolded p63 mutant protein leads to severe epidermal defects. Variants of p63 that abolish aggregation of the mutant proteins are able to rescue p63’s transcriptional function in reporter assays as well as in a human fibroblast-to-keratinocyte conversion assay. Our studies reveal that AEC syndrome is a protein aggregation disorder and opens avenues for therapeutic intervention.
Regulation of the stability of RGF1 receptor by the ubiquitin-specific proteases UBP12/UBP13 is critical for root meristem maintenance
Authors: An Zhichao , Liu Yuliang , Ou Yang , Li Jia , Zhang Baowen , Sun Daye , Sun Yu , Tang Wenqiang
Published: January 2018

Significance

Reversible ubiquitination regulates cellular protein abundance. The receptor-like kinase (RLK) RGFR1 plays an important role in regulating root meristem development. Upon ligand binding, activated RGFR1 is ubiquitinated and eventually degraded by the 26S proteasome. In this study, we found that the ubiquitin-specific proteases UBP12 and UBP13 are components of the RGFR1 signaling pathway. UBP13 interacts directly with RGFR1 and can counteract the ligand-induced ubiquitination and degradation of RGFR1. Our discovery provides insight into the dynamic regulation of cell-surface RLKs, which may serve to fine-tune the sensitivity of plant cells to extracellular stimuli.
Uncovering the role of the East Asian jet stream and heterogeneities in atmospheric rivers affecting the western United States
Authors: Zhang Wei , Villarini Gabriele
Published: January 2018

Significance

Atmospheric rivers (ARs) have major socioeconomic repercussions along the US West Coast due to heavy rainfall, flooding, strong winds, and storm surge. However, our understanding of the physical drivers responsible for their interannual variability is still limited, with different climate modes identified as possible mechanisms. Here we find that the Pacific-Japan teleconnections/patterns and the East Asian subtropical jet exhibit the strongest linkage with the total frequency of landfalling ARs affecting the western United States, much stronger than the other potential climate modes previously considered. We also uncover heterogeneities in AR tracks; specifically, not all ARs making landfall along the US West Coast come from a single population, but rather it is possible to stratify them into three main clusters.
Cytocapsular tubes conduct cell translocation
Authors: Yi Tingfang , Wagner Gerhard
Published: January 2018

Significance

Cell migration in multicellular organisms is crucial for embryonic development, immune responses, organ homeostasis, tissue regeneration, and tumor metastasis. However, mechanisms of cell locomotion in tissues are elusive. Here we report that single mammalian cells generate extracellular and membranous cytocapsular tubes as highways for directed cell transportation. Cytocapsular tubes interconnect and form tubular networks for directed cell transportation in multiple directions. Increased eukaryotic translation initiation factor eIF4E-mediated cap-dependent translation initiation promotes cytocapsular tube development. This study reveals that cytocapsular tubes provide membranous tubes for directed cell translocation.
HIF signaling in osteoblast-lineage cells promotes systemic breast cancer growth and metastasis in mice
Authors: Devignes Claire-Sophie , Aslan Yetki , Brenot Audrey , Devillers Audrey , Schepers Koen , Fabre Stéphanie , Chou Jonathan , Casbon Amy-Jo , Werb Zena , Provot Sylvain
Published: January 2018

Significance

Previous work showed that primary tumors instigate systemic macroenvironmental changes supporting cancer progression and metastasis. Here, we show that activation of HIF signaling in osteoblast-lineage cells also generates systemic changes promoting breast cancer growth and dissemination in bones and outside the skeleton. Our results indicate that loss of bone homeostasis through alterations of the bone anabolism could affect breast cancer progression and present the skeleton as an important organ of the tumor macroenvironment. They also suggest that targeting the bone microenvironment could limit systemic tumor growth and dissemination in breast cancer.
Mindfulness under neoliberal governmentality: critiquing the operation of biopower in corporate mindfulness and constructing queer alternatives
Authors: Walsh Zack
Published: January 2018

At the heart of many mindfulness critiques is essentially a critique of how mindfulness has been rebranded to promote neoliberal governmentality and produce neoliberal subjects. Most critics of corporate mindfulness don’t argue that teaching mindfulness in a corporate setting
is a problem in itself – they are more specifically critiquing the broader notion of corporate mindfulness, as a management tool whose various entanglements with neoliberal governmentality subordinate mindfulness practitioners to larger systemic issues related to how stress is generated
and how mindfulness is used to alleviate the symptoms, rather than systemic sources of stress. In this paper, I will argue that mindfulness programs provide effective regulatory mechanisms for biopower to extend neoliberal logics of control to internal conditioning processes, and I will articulate
ways in which one might alternatively conceive and practice mindfulness not only to resist neoliberal governmentality, but also to affirm the lives that it subjugates.
Quantifying exosome secretion from single cells reveals a modulatory role for GPCR signaling
Authors: Verweij Frederik Johannes , Bebelman Maarten P. , Jimenez Connie R. , Garcia-Vallejo Juan J. , Janssen Hans , Neefjes Jacques , Knol Jaco C. , de Goeij-de Haas Richard , Piersma Sander R. , Baglio S. Rubina , Verhage Matthijs , Middeldorp Jaap M. , Zomer Anoek , van Rheenen Jacco , Coppolino Marc G. , Hurbain Ilse , Raposo Graça , Smit Martine J. , Toonen Ruud F.G. , van Niel Guillaume , Pegtel D. Michiel
Published: January 2018

Exosomes are small endosome-derived extracellular vesicles implicated in cell–cell communication and are secreted by living cells when multivesicular bodies (MVBs) fuse with the plasma membrane (PM). Current techniques to study exosome physiology are based on isolation procedures after secretion, precluding direct and dynamic insight into the mechanics of exosome biogenesis and the regulation of their release. In this study, we propose real-time visualization of MVB–PM fusion to overcome these limitations. We designed tetraspanin-based pH-sensitive optical reporters that detect MVB–PM fusion using live total internal reflection fluorescence and dynamic correlative light–electron microscopy. Quantitative analysis demonstrates that MVB–PM fusion frequency is reduced by depleting the target membrane SNAREs SNAP23 and syntaxin-4 but also can be induced in single cells by stimulation of the histamine H1 receptor (H1HR). Interestingly, activation of H1R1 in HeLa cells increases Ser110 phosphorylation of SNAP23, promoting MVB–PM fusion and the release of CD63-enriched exosomes. Using this single-cell resolution approach, we highlight the modulatory dynamics of MVB exocytosis that will help to increase our understanding of exosome physiology and identify druggable targets in exosome-associated pathologies.
SPR2 protects minus ends to promote severing and reorientation of plant cortical microtubule arrays
Authors: Nakamura Masayoshi , Lindeboom Jelmer J. , Saltini Marco , Mulder Bela M. , Ehrhardt David W.
Published: January 2018

The cortical microtubule arrays of higher plants are organized without centrosomes and feature treadmilling polymers that are dynamic at both ends. The control of polymer end stability is fundamental for the assembly and organization of cytoskeletal arrays, yet relatively little is understood about how microtubule minus ends are controlled in acentrosomal microtubule arrays, and no factors have been identified that act at the treadmilling minus ends in higher plants. Here, we identify Arabidopsis thaliana SPIRAL2 (SPR2) as a protein that tracks minus ends and protects them against subunit loss. SPR2 function is required to facilitate the rapid reorientation of plant cortical arrays as stimulated by light perception, a process that is driven by microtubule severing to create a new population of microtubules. Quantitative live-cell imaging and computer simulations reveal that minus protection by SPR2 acts by an unexpected mechanism to promote the lifetime of potential SPR2 severing sites, increasing the likelihood of severing and thus the rapid amplification of the new microtubule array.
Rewired Notch/p53 by Numb’ing Mdm2
Authors: Kim Hyungsoo , Ronai Ze’ev A.
Published: January 2018

Although numerous pathways are known to control the tumor suppressor protein p53, coordinated regulation of the p53–Notch axis by Numb may have an even more remarkable impact. In this issue, Colaluca at al. (2018. J. Cell Biol. https://doi.org/10.1083/jcb.201709092) reveal an unexpected role of a newly characterized Numb splice variant in the regulation of p53, which may have significant implications for therapeutic intervention in breast cancer.
LIGHT–HVEM signaling in keratinocytes controls development of dermatitis
Authors: Herro Rana , Shui Jr-Wen , Zahner Sonja , Sidler Daniel , Kawakami Yuko , Kawakami Toshiaki , Tamada Koji , Kronenberg Mitchell , Croft Michael
Published: January 2018

Dermatitis is often associated with an allergic reaction characterized by excessive type 2 responses leading to epidermal acanthosis, hyperkeratosis, and dermal inflammation. Although factors like IL-4, IL-13, and thymic stromal lymphopoietin (TSLP) are thought to be instrumental for the development of this type of skin disorder, other cytokines may be critical. Here, we show that the tumor necrosis factor (TNF) superfamily protein LIGHT (homologous to lymphotoxin, exhibits inducible expression, and competes with HSV glycoprotein D for binding to HVEM, a receptor expressed on T lymphocytes) is required for experimental atopic dermatitis, and LIGHT directly controls keratinocyte hyperplasia, and production of periostin, a matricellular protein that contributes to the clinical features of atopic dermatitis as well as other skin diseases such as scleroderma. Mice with a conditional deletion of the LIGHT receptor HVEM (herpesvirus entry mediator) in keratinocytes phenocopied LIGHT-deficient mice in exhibiting reduced epidermal thickening and dermal collagen deposition in a model of atopic dermatitis driven by house dust mite allergen. LIGHT signaling through HVEM in human epidermal keratinocytes directly induced proliferation and periostin expression, and both keratinocyte-specific deletion of HVEM or antibody blocking of LIGHT–HVEM interactions after disease onset prevented expression of periostin and limited atopic dermatitis symptoms. Developing reagents that neutralize LIGHT–HVEM signaling might be useful for therapeutic intervention in skin diseases where periostin is a central feature.
Targeting IRF3 as a YAP agonist therapy against gastric cancer
Authors: Jiao Shi , Guan Jingmin , Chen Min , Wang Wenjia , Li Chuanchuan , Wang Yugong , Cheng Yunfeng , Zhou Zhaocai
Published: January 2018

The Hippo pathway plays a vital role in tissue homeostasis and tumorigenesis. The transcription factor IRF3 is essential for innate antiviral immunity. In this study, we discovered IRF3 as an agonist of Yes-associated protein (YAP). The expression of IRF3 is positively correlated with that of YAP and its target genes in gastric cancer; the expression of both IRF3 and YAP is up-regulated and prognosticates patient survival. IRF3 interacts with both YAP and TEAD4 in the nucleus to enhance their interaction, promoting nuclear translocation and activation of YAP. IRF3 and YAP–TEAD4 are associated genome-wide to cobind and coregulate many target genes of the Hippo pathway. Overexpression of active IRF3 increased, but depletion of IRF3 reduced, the occupancy of YAP on the target genes. Knockdown or pharmacological targeting of IRF3 by Amlexanox, a drug used clinically for antiinflammatory treatment, inhibits gastric tumor growth in a YAP-dependent manner. Collectively, our study identifies IRF3 as a positive regulator for YAP, highlighting a new therapeutic target against YAP-driven cancers.
Ontogeny of human mucosal-associated invariant T cells and related T cell subsets
Authors: Ben Youssef Ghada , Tourret Marie , Salou Marion , Ghazarian Liana , Houdouin Véronique , Mondot Stanislas , Mburu Yvonne , Lambert Marion , Azarnoush Saba , Diana Jean-Sébastien , Virlouvet Anne-Laure , Peuchmaur Michel , Schmitz Thomas , Dalle Jean-Hugues , Lantz Olivier , Biran Valérie , Caillat-Zucman Sophie
Published: January 2018

Mucosal-associated invariant T (MAIT) cells are semi-invariant Vα7.2+ CD161highCD4− T cells that recognize microbial riboflavin precursor derivatives such as 5-OP-RU presented by MR1. Human MAIT cells are abundant in adult blood, but there are very few in cord blood. We longitudinally studied Vα7.2+ CD161high T cell and related subset levels in infancy and after cord blood transplantation. We show that Vα7.2+ and Vα7.2− CD161high T cells are generated early during gestation and likely share a common prenatal developmental program. Among cord blood Vα7.2+ CD161high T cells, the minority recognizing MR1:5-OP-RU display a TRAV/TRBV repertoire very similar to adult MAIT cells. Within a few weeks of life, only the MR1:5-OP-RU reactive Vα7.2+ CD161high T cells acquire a memory phenotype. Only these cells expand to form the adult MAIT pool, diluting out other Vα7.2+ CD161high and Vα7.2− CD161high populations, in a process requiring at least 6 years to reach adult levels. Thus, the high clonal size of adult MAIT cells is antigen-driven and likely due to the fine specificity of the TCRαβ chains recognizing MR1-restricted microbial antigens.
Immune system: The “seventh sense”
Authors: Kipnis Jonathan
Published: January 2018

The brain is our computing machine that integrates stimuli from the environment and orchestrates responses to these stimuli. Here, I propose that the defining role of the immune system is to sense microorganisms and to inform the brain about them.
Association of early- and adult-life socioeconomic circumstances with muscle strength in older age
Authors: Cheval Boris , Boisgontier Matthieu P , Orsholits Dan , Sieber Stefan , Guessous Idris , Gabriel Rainer , Stringhini Silvia , Blane David , van der Linden Bernadette W A , Kliegel Matthias , Burton-Jeangros Claudine , Courvoisier Delphine S , Cullati Stéphane
Published: January 2018

Background

socioeconomic circumstances (SEC) during a person’s lifespan influence a wide range of health outcomes. However, solid evidence of the association of early- and adult-life SEC with health trajectories in ageing is still lacking. This study assessed whether early-life SEC are associated with muscle strength in later life—a biomarker of health—and whether this relationship is caused by adult-life SEC and health behaviours.

Methods

we used data from the Survey of Health Ageing and Retirement in Europe, a 12-year population-based cohort study with repeated measurement in six waves (2004–15) and retrospective collection of life-course data. Participants’ grip strength was assessed by using a handheld dynamometer. Confounder-adjusted logistic mixed-effect models were used to examine the associations of early- and adult-life SEC with the risk of low muscle strength (LMS) in older age.

Results

a total of 24,179 participants (96,375 observations) aged 50–96 living in 14 European countries were included in the analyses. Risk of LMS was increased with disadvantaged relative to advantaged early-life SEC. The association between risk of LMS and disadvantaged early-life SEC gradually decreased when adjusting for adult-life SEC for both sexes and with unhealthy behaviours for women. After adjusting for these factors, all associations between risk of LMS and early-life SEC remained significant for women.

Conclusion

early-life SEC are associated with muscle strength after adjusting for adult-life SEC and behavioural lifestyle factors, especially in women, which suggests that early life may represent a sensitive period for future health.
Central Blood Pressure Responses to Dietary Sodium and Potassium Interventions
Authors: Xing Xiaolong , Liu Fangchao , Yang Xueli , Huang Chen , Zhang Dingding , Chen Shufeng , Chen Jichun , Li Jianxin , Liu Zhendong , Lu Fanghong , Gu Dongfeng , Huang Jianfeng
Published: January 2018

BACKGROUND

To explore how central hemodynamics respond to dietary sodium and potassium interventions, and whether the responses are associated with metabolic traits.

METHODS

We conducted a dietary intervention study including a 7-day low-sodium (51.3 mmol sodium/day) intervention, a 7-day high-sodium (307.8 mmol sodium/day) intervention, and a 7-day high-sodium with potassium supplementation (60.0 mmol potassium/day) intervention among 99 northern Chinese subjects aged 18–60 years. Five metabolic traits included abdominal obesity, high triglycerides, low HDL cholesterol, raised blood pressure (BP), and high glucose. Central hemodynamics were measured at baseline and during each intervention.

RESULTS

Central systolic BP (SBP), diastolic BP (DBP), pulse pressure (PP), and augmentation index (AIx@75) significantly decreased during low-sodium intervention, increased during high-sodium intervention, and then decreased during potassium supplementation. We observed potential linear trends toward significance of central SBP and PP responses to low-sodium intervention, and significant linear trends of responses to high-sodium intervention as the number of metabolic traits grows. For example, among participants with 0 or 1, 2 or 3, and 4 or 5 metabolic traits, central SBP responses to high-sodium intervention were 8.8 [95% confidence interval (5.8, 11.8)], 9.3 (7.1, 11.6), and 14.0 (11.6, 16.3) mmHg, respectively (P for trend = 0.009). Significant linear trends of central SBP and DBP responses to potassium supplementation were also observed.

CONCLUSIONS

Central BP and AIx@75 were lowered by sodium reduction and potassium supplementation, and elevated by sodium-loading. The responses of central BP were pronounced among individuals with metabolic traits clustering.

CLINICAL TRIALS REGISTRATION

Trial Number NCT00721721 (The current study is registered on ClinicalTrials.gov; https://clinicaltrials.gov).
How to design a single-cell RNA-sequencing experiment: pitfalls, challenges and perspectives
Authors: Dal Molin Alessandra , Di Camillo Barbara
Published: January 2018

The sequencing of the transcriptome of single cells, or single-cell RNA-sequencing, has now become the dominant technology for the identification of novel cell types in heterogeneous cell populations or for the study of stochastic gene expression. In recent years, various experimental methods and computational tools for analysing single-cell RNA-sequencing data have been proposed. However, most of them are tailored to different experimental designs or biological questions, and in many cases, their performance has not been benchmarked yet, thus increasing the difficulty for a researcher to choose the optimal single-cell transcriptome sequencing (scRNA-seq) experiment and analysis workflow. In this review, we aim to provide an overview of the current available experimental and computational methods developed to handle single-cell RNA-sequencing data and, based on their peculiarities, we suggest possible analysis frameworks depending on specific experimental designs. Together, we propose an evaluation of challenges and open questions and future perspectives in the field. In particular, we go through the different steps of scRNA-seq experimental protocols such as cell isolation, messenger RNA capture, reverse transcription, amplification and use of quantitative standards such as spike-ins and Unique Molecular Identifiers (UMIs). We then analyse the current methodological challenges related to preprocessing, alignment, quantification, normalization, batch effect correction and methods to control for confounding effects.
PhenoRank: reducing study bias in gene prioritization through
simulation
Authors: Cornish Alex J , David Alessia , Sternberg Michael J E
Published: January 2018

Motivation

Genome-wide association studies have identified thousands of loci associated with human disease, but identifying the causal genes at these loci is often difficult. Several methods prioritize genes most likely to be disease causing through the integration of biological data, including protein–protein interaction and phenotypic data. Data availability is not the same for all genes however, potentially influencing the performance of these methods.

Results

We demonstrate that whilst disease genes tend to be associated with greater numbers of data, this may be at least partially a result of them being better studied. With this observation we develop PhenoRank, which prioritizes disease genes whilst avoiding being biased towards genes with more available data. Bias is avoided by comparing gene scores generated for the query disease against gene scores generated using simulated sets of phenotype terms, which ensures that differences in data availability do not affect the ranking of genes. We demonstrate that whilst existing prioritization methods are biased by data availability, PhenoRank is not similarly biased. Avoiding this bias allows PhenoRank to effectively prioritize genes with fewer available data and improves its overall performance. PhenoRank outperforms three available prioritization methods in cross-validation (PhenoRank area under receiver operating characteristic curve [AUC]=0.89, DADA AUC = 0.87, EXOMISER AUC = 0.71, PRINCE AUC = 0.83, P < 2.2 × 10−16).

Availability and implementation

PhenoRank is freely available for download at https://github.com/alexjcornish/PhenoRank.

Supplementary information

Supplementary data are available at Bioinformatics online.
From genetics to response to injury: vascular smooth muscle cells in aneurysms and dissections of the ascending aorta
Authors: Michel Jean-Baptiste , Jondeau Guillaume , Milewicz Dianna M
Published: January 2018

Vascular smooth muscle cells (vSMCs) play a crucial role in both the pathogenesis of Aneurysms and Dissections of the ascending thoracic aorta (TAAD) in humans and in the associated adaptive compensatory responses, since thrombosis and inflammatory processes are absent in the majority of cases. Aneurysms and dissections share numerous characteristics, including aetiologies and histopathological alterations: vSMC disappearance, medial areas of mucoid degeneration, and extracellular matrix (ECM) breakdown. Three aetiologies predominate in TAAD in humans: (i) genetic causes in heritable familial forms, (ii) an association with bicuspid aortic valves, and (iii) a sporadic degenerative form linked to the aortic aging process. Genetic forms include mutations in vSMC genes encoding for molecules of the ECM or the TGF-β pathways, or participating in vSMC tone. On the other hand, aneurysms and dissections, whatever their aetiologies, are characterized by an increase in wall permeability leading to transmural advection of plasma proteins which could interact with vSMCs and ECM components. In this context, blood-borne plasminogen appears to play an important role, because its outward convection through the wall is increased in TAAD, and it could be converted to active plasmin at the vSMC membrane. Active plasmin can induce vSMC disappearance, proteolysis of adhesive proteins, activation of MMPs and release of TGF-β from its ECM storage sites. Conversely, vSMCs could respond to aneurysmal biomechanical and proteolytic injury by an epigenetic phenotypic switch, including constitutional overexpression and nuclear translocation of Smad2 and an increase in antiprotease and ECM protein synthesis. In contrast, such an epigenetic phenomenon is not observed in dissections. In this context, dysfunction of proteins involved in vSMC tone are interesting to study, particularly in interaction with plasma protein transport through the wall and TGF-β activation, to establish the relationship between these dysfunctions and ECM proteolysis.
On linear-quadratic optimal control of implicit difference equations
Authors: Bankmann Daniel , Voigt Matthias
Published: January 2018

In this work we investigate explicit and implicit difference equations and the corresponding infinite time horizon linear-quadratic optimal control problem. We derive conditions for feasibility of the optimal control problem as well as existence and uniqueness of optimal controls under certain weaker assumptions compared to the standard approaches in the literature which are using algebraic Riccati equations. To this end, we introduce and analyse a discrete-time Lur’e equation and a corresponding Kalman–Yakubovich–Popov (KYP) inequality. We show that solvability of the KYP inequality can be characterized via the spectral structure of a certain palindromic matrix pencil. The deflating subspaces of this pencil are finally used to construct solutions of the Lur’e equation. The results of this work are transferred from the continuous-time case. However, many additional technical difficulties arise in this context.
Asymptotics of Hankel Determinants With a One-Cut Regular Potential and Fisher–Hartwig Singularities
Authors: Charlier Christophe
Published: January 2018

We obtain asymptotics of large Hankel determinants whose weight depends on a one-cut regular potential and any number of Fisher–Hartwig singularities. This generalises two results: (1) a result of Berestycki, Webb, and Wong [5] for root-type singularities and (2) a result of Its and Krasovsky [37] for a Gaussian weight with a single jump-type singularity. We show that when we apply a piecewise constant thinning on the eigenvalues of a random Hermitian matrix drawn from a one-cut regular ensemble, the gap probability in the thinned spectrum, as well as correlations of the characteristic polynomial of the associated conditional point process, can be expressed in terms of these determinants.
The Rust Fungus Melampsora larici-populina Expresses a Conserved Genetic Program and Distinct Sets of Secreted Protein Genes During Infection of Its Two Host Plants, Larch and Poplar
Authors: Lorrain Cécile , Marchal Clémence , Hacquard Stéphane , Delaruelle Christine , Pétrowski Jérémy , Petre Benjamin , Hecker Arnaud , Frey Pascal , Duplessis Sébastien
Published: January 2018

Mechanisms required for broad-spectrum or specific host colonization of plant parasites are poorly understood. As a perfect illustration, heteroecious rust fungi require two alternate host plants to complete their life cycles. Melampsora larici-populina infects two taxonomically unrelated plants, larch, on which sexual reproduction is achieved, and poplar, on which clonal multiplication occurs, leading to severe epidemics in plantations. We applied deep RNA sequencing to three key developmental stages of M. larici-populina infection on larch: basidia, pycnia, and aecia, and we performed comparative transcriptomics of infection on poplar and larch hosts, using available expression data. Secreted protein was the only significantly overrepresented category among differentially expressed M. larici-populina genes between the basidial, the pycnial, and the aecial stages, highlighting their probable involvement in the infection process. Comparison of fungal transcriptomes in larch and poplar revealed a majority of rust genes were commonly expressed on the two hosts and a fraction exhibited host-specific expression. More particularly, gene families encoding small secreted proteins presented striking expression profiles that highlight probable candidate effectors specialized on each host. Our results bring valuable new information about the biological cycle of rust fungi and identify genes that may contribute to host specificity.
Microbial Communities Associated with Storage Onion
Authors: Yurgel Svetlana N. , Abbey Lord , Loomer Nancy , Gillis-Madden Rosalie , Mammoliti Melissa
Published: January 2018

Onion (Allium cepa) bulb rot is an important pathological problem worldwide, as it is caused by diverse pathogens, bacterial and fungal. The diversity and structure of microbial communities associated with apparently healthy and diseased onion bulbs were analyzed. The community-based approach allowed identification of a number of potential pathogenic microorganisms associated with onion bulbs affected by disease under storage environments. Enterobacteriaceae, Burkholderia, Gluconobacter, Acinetobacter, Pseudomonas, Citrobacter, Nectriaceae, Botrytis, Wickerhamomyces, Penicillium, and Candida were the most relatively abundant bacterial and fungal taxa in the diseased onion bulb dataset. It was found that these taxa are also widely distributed in the bulbs without apparent disease symptoms. Additionally, several potential fermenters were detected in onion tissue. These data suggest that, in addition to abiotic factors, fermentation plays a role in the storage spoilage of onion bulbs. It was also shown that bacterial and fungal communities differ in their diversity and structure between individual onions affected by bulb rot. The identification of dinoflagellates Symbiodinium in onion bulbs suggested that this eukaryote might have a much broader spectrum of habitats and eukaryotic hosts.
Using Iterative Plan-Do-Study-Act Cycles to Improve Teaching Pedagogy
Authors: Murray Elizabeth J.
Published: January 2018

Most students entering nursing programs today are members of Generation Y or the Millennial generation, and they learn differently than previous generations. Nurse educators must consider implementing innovative teaching strategies that appeal to the newest generation of learners. The Plan-Do-Study-Act cycle is a framework that can be helpful when planning, assessing, and continually improving teaching pedagogy. This article describes the use of iterative Plan-Do-Study-Act cycles to implement a change in teaching pedagogy.
Utilization of Apical Vaginal Support Procedures at Time of Inpatient Hysterectomy Performed for Benign Conditions: A National Estimate
Authors: Ross Whitney Trotter , Meister Melanie R. , Shepherd Jonathan P. , Olsen Margaret A. , Lowder Jerry L.
Published: January 2018

(Abstracted from Am J Obstet Gynecol 2017;217:436.e1–436.e8)

The most critical component of apical vaginal support is compromised at time of total hysterectomy unless specific apical support procedures (ASPs) are performed. When level I support is lost in women without prolapse and not reestablished in those with prolapse, these patients may be at risk of future vaginal vault prolapse.
Foley Catheterisation Versus Oral Misoprostol for Induction of Labour in Hypertensive Women in India (INFORM): A Multicentre, Open-Label, Randomised Controlled Trial
Authors: Mundle Shuchita , Bracken Hillary , Khedikar Vaishali , Mulik Jayashree , Faragher Brian , Easterling Thomas , Leigh Simon , Granby Paul , Haycox Alan , Turner Mark A. , Alfirevic Zarko , Winikoff Beverly , Weeks Andrew D.
Published: January 2018

(Abstracted from Lancet 2017;390:669–680)

Hypertensive disorders of pregnancy such as preeclampsia are leading causes of maternal morbidity and mortality worldwide and can be reduced by an expeditious delivery. In places where resources are scarce (both personnel and equipment to carefully monitor mother and child during labor), 2 inexpensive methods of induction to more quickly get active labor going are recommended by the World Health Organization: use of a transcervical Foley catheter or low-dose oral misoprostol pills.
Aspirin Versus Placebo in Pregnancies at High Risk for Preterm Preeclampsia
Authors: Rolnik Daniel L. , Wright David , Poon Liona C. , O’Gorman Neil , Syngelaki Argyro , de Paco Matallana Catalina , Akolekar Ranjit , Cicero Simona , Janga Deepa , Singh Mandeep , Molina Francisca S. , Persico Nicola , Jani Jacques C. , Plasencia Walter , Papaioannou George , Tenenbaum-Gavish Kinneret , Meiri Hamutal , Gizurarson Sveinbjorn , Maclagan Kate , Nicolaides Kypros H.
Published: January 2018

(Abstracted from N Engl J Med 2017;377:613–622)

Since 1979, multiple studies have shown that low-dose aspirin in pregnancy can lower the occurrence of preeclampsia. Subsequent studies have shown that doses greater than 100 mg/d started before 16 weeks of gestation are most effective.
Children’s Recognition of Emotional Prosody in Spectrally Degraded Speech Is Predicted by Their Age and Cognitive Status
Authors: Tinnemore Anna R. , Zion Danielle J. , Kulkarni Aditya M. , Chatterjee Monita
Published: January 2018

Objectives:

It is known that school-aged children with cochlear implants show deficits in voice emotion recognition relative to normal-hearing peers. Little, however, is known about normal-hearing children’s processing of emotional cues in cochlear implant–simulated, spectrally degraded speech. The objective of this study was to investigate school-aged, normal-hearing children’s recognition of voice emotion, and the degree to which their performance could be predicted by their age, vocabulary, and cognitive factors such as nonverbal intelligence and executive function.

Design:

Normal-hearing children (6–19 years old) and young adults were tested on a voice emotion recognition task under three different conditions of spectral degradation using cochlear implant simulations (full-spectrum, 16-channel, and 8-channel noise-vocoded speech). Measures of vocabulary, nonverbal intelligence, and executive function were obtained as well.

Results:

Adults outperformed children on all tasks, and a strong developmental effect was observed. The children’s age, the degree of spectral resolution, and nonverbal intelligence were predictors of performance, but vocabulary and executive functions were not, and no interactions were observed between age and spectral resolution.

Conclusions:

These results indicate that cognitive function and age play important roles in children’s ability to process emotional prosody in spectrally degraded speech. The lack of an interaction between the degree of spectral resolution and children’s age further suggests that younger and older children may benefit similarly from improvements in spectral resolution. The findings imply that younger and older children with cochlear implants may benefit similarly from technical advances that improve spectral resolution.
S1 Sacrectomy for Re-recurrent Rectal Cancer: Our Experience with Reconstruction Using an Expandable Vertebral Body Replacement Device
Authors: Lee Daniel Jin Keat , Wang Kelvin Yafan , Sagar Peter Michael , Timothy Jake
Published: January 2018

INTRODUCTION:

R0 resection is achieved by high sacrectomy for local recurrence of colorectal cancer, but significant rates of perioperative complications and long-term patient morbidity are associated with this procedure. In this report, we outline our unique experience of using an expandable cage for vertebral body reconstruction following S1 sacrectomy in a 66-year-old patient with re-recurrent rectal cancer. We aim to highlight several key steps, with a view to improving postoperative outcomes.

TECHNIQUE:

A midline laparotomy was performed with the patient in supine Lloyd-Davies position, demonstrating recurrence of tumor at the S1 vertebral body. Subtotal vertebral body excision of S1 with sparing of the posterior wall and ventral foramina was completed by using an ultrasonic bone aspirator. Reconstruction was performed using an expandable corpectomy spacer system. The system was assembled and expanded in situ to optimally bridge the corpectomy. The device was secured into the L5 and S2 vertebrae by means of angled end plate screws superiorly and inferiorly. Bone grafts were positioned adjacent to the implant after this.

RESULTS:

Total operating time was 266 minutes with 350 mL of intraoperative blood loss. There were no immediate postoperative complications. The patient did not report any back pain at the time of discharge, and no neurological deficit was reported or identified. Postoperative CT scan showed excellent vertebral alignment and preservation of S1 height.

CONCLUSION:

We conclude that high sacrectomy with an expandable metal cage is feasible in the context of re-recurrent rectal cancer when consideration is given to the method of osteotomy and vertebral body replacement.
Survival Benefit of Japanese Extended Lymphadenectomy for Clinically Node-Negative and Node-Positive Colorectal Cancers
Authors: Ouchi Akira , Komori Koji , Kimura Kenya , Kinoshita Takashi , Shimizu Yasuhiro , Nagino Masato
Published: January 2018

BACKGROUND:

The impact of extended lymphadenectomy for colorectal cancer is still not sufficiently clear.

OBJECTIVE:

The aim of the present study was to evaluate the survival benefit of extended lymphadenectomy compared with nonextended lymphadenectomy for clinically node-negative and node-positive colorectal cancers.

DESIGN:

The present study was a retrospective cohort study that used prospectively collected data and a propensity score matching method.

SETTINGS:

The present study was conducted at a single specialized colorectal surgery department.

PATIENTS:

Of the 1314 patients who underwent radical resection with nonextended or extended lymphadenectomy between 1988 and 2007, we included 711 and 603 patients in the cN0 and cN1/2 series. Propensity score matching was applied, and 141 and 63 pairs were extracted from the cN0 and cN1/2 series.

MAIN OUTCOME MEASURES:

Disease-free survival, cancer-specific survival, and overall survival of the 2 groups were calculated and compared.

RESULTS:

In the cN0 series, no differences were observed in the long-term outcomes between the nonextended and extended groups. In the cN1/2 series, the disease-free survival tended to be higher, and the cancer-specific survival and overall survival were significantly higher (log rank, p = 0.04, p = 0.02, and p = 0.01, respectively), but the frequency of local recurrence was significantly lower (p = 0.04) in the extended group.

LIMITATIONS:

The present study was limited by its nonrandomized retrospective design.

CONCLUSIONS:

Extended lymphadenectomy demonstrated a good inhibitory effect on the local recurrence rate and led to improved disease-free survival, cancer-specific survival, and overall survival of patients in the cN1/2 series. See Video Abstract at http://links.lww.com/DCR/A517.
Morbidity Following Coloanal Anastomosis: A Comparison of Colonic J-Pouch vs Straight Anastomosis
Authors: Brown Shaun , Margolin David A. , Altom Laura K. , Green Heather , Beck David E. , Kann Brian R. , Whitlow Charles B. , Vargas Herschel David
Published: January 2018

BACKGROUND:

Low rectal tumors are often treated with sphincter-preserving resection followed by coloanal anastomosis.

OBJECTIVE:

The purpose of this study was to compare the short-term complications following straight coloanal anastomosis vs colonic J-pouch anal anastomosis.

DESIGN:

Patients were identified who underwent proctectomy for rectal neoplasia followed by coloanal anastomosis in the 2008 to 2013 American College of Surgeons National Surgical Quality Improvement Program database. Demographic characteristics and 30-day postoperative complications were compared between groups.

SETTINGS:

A national sample was extracted from the American College of Surgeons National Surgical Quality Improvement Project database.

PATIENTS:

Inpatients following proctectomy and coloanal anastomosis for rectal cancer were selected.

MAIN OUTCOME MEASURES:

Demographic characteristics and 30-day postoperative complications were compared between the 2 groups.

RESULTS:

One thousand three hundred seventy patients were included, 624 in the straight anastomosis group and 746 in the colonic J-pouch group. Preoperative characteristics were similar between groups, with the exception of preoperative radiation therapy (straight anastomosis 35% vs colonic J-pouch 48%, p = 0.0004). Univariate analysis demonstrated that deep surgical site infection (3.7% vs 1.4%, p = 0.01), septic shock (2.25% vs 0.8%, p = 0.04), and return to the operating room (8.8% vs 5.0%, p = 0.0006) were more frequent in the straight anastomosis group vs the colonic J-pouch group. Major complications were also higher (23% vs 14%, p = 0.0001) and length of stay was longer in the straight anastomosis group vs the colonic J-pouch group (8.9 days vs 8.1 days, p = 0.02). After adjusting for covariates, major complications were less following colonic J-pouch vs straight anastomosis (OR, 0.57; CI, 0.38–0.84; p = 0.005). Subgroup analysis of patients who received preoperative radiation therapy demonstrated no difference in major complications between groups.

LIMITATIONS:

This study had those limitations inherent to a retrospective study using an inpatient database.

CONCLUSION:

Postoperative complications were less following colonic J-pouch anastomosis vs straight anastomosis. Patients who received preoperative radiation had similar rates of complications, regardless of the reconstructive technique used following low anterior resection. See Video Abstract at http://links.lww.com/DCR/A468.