bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bacteria‐induced production of the antibacterial sesquiterpene lagopodin B inCoprinopsis cinerea
Authors: Stöckli Martina , Morinaka Brandon I. , Lackner Gerald , Kombrink Anja , Sieber Ramon , Margot Céline , Stanley Claire E. , deMello Andrew J. , Piel Jörn , Künzler Markus 
Published: May 2019

SummaryFungi defend their ecological niche against antagonists by producing antibiosis molecules. Some of these molecules are only produced upon confrontation with the antagonist. The basidiomyceteCoprinopsis cinereainduces the expression of the sesquiterpene synthase‐encoding genecop6and its two neighboring genes coding for cytochrome P450 monooxygenases in response to bacteria. We further investigated this regulation ofcop6and examined if the gene product is involved in the production of antibacterials. Cell‐free supernatants of axenic cultures of the Gram‐positive bacteriumBacillus subtiliswere sufficient to inducecop6transcription assessed using a fluorescent reporter strain. Use of this strain in a microfluidic device revealed that thecop6gene was induced in all hyphae directly exposed to the supernatant and that induction occurred within less than one hour. Targeted replacement of thecop6gene demonstrated the requirement of the encoded synthase for the biosynthesis of the sesquiterpene lagopodin B, a previously reported antibacterial compound from related species. Accordingly, lagopodin B fromC. cinereainhibited the growth of several Gram‐positive bacteria includingB. subtilisbut not Gram‐negative bacteria. Our results demonstrate that theC. cinereavegetative mycelium responds to soluble compounds of a bacterial culture supernatant by local production of an antibacterial secondary metabolite.
Defense of pyrethrum flowers: repelling herbivores and recruiting carnivores by producing aphid alarm pheromone
Authors: Li Jinjin , Hu Hao , Mao Jing , Yu Lu , Stoopen Geert , Wang Manqun , Mumm Roland , de Ruijter Norbert C. A. , Dicke Marcel , Jongsma Maarten A. , Wang Caiyun 
Published: May 2019

Summary

(E)‐β‐Farnesene (EβF) is the predominant constituent of the alarm pheromone of most aphid pest species. Moreover, natural enemies of aphids use EβF to locate their aphid prey. Some plant species emit EβF, potentially as a defense against aphids, but field demonstrations are lacking.

Here, we present field and laboratory studies of flower defense showing that ladybird beetles are predominantly attracted to young stage‐2 pyrethrum flowers that emitted the highest and purest levels of EβF. By contrast, aphids were repelled by EβF emitted by S2 pyrethrum flowers. Although peach aphids can adapt to pyrethrum plants in the laboratory, aphids were not recorded in the field.

Pyrethrum's (E)‐β‐farnesene synthase (EbFS) gene is strongly expressed in inner cortex tissue surrounding the vascular system of the aphid‐preferred flower receptacle and peduncle, leading to elongated cells filled with EβF. Aphids that probe these tissues during settlement encounter and ingest plant EβF, as evidenced by the release in honeydew. These EβF concentrations in honeydew induce aphid alarm responses, suggesting an extra layer of this defense.

Collectively, our data elucidate a defensive mimicry in pyrethrum flowers: the developmentally regulated and tissue‐specific EβF accumulation and emission both prevents attack by aphids and recruits aphid predators as bodyguards.
Identification and verification of quantitative trait loci for eating and cooking quality of rice (Oryza sativa)
Authors: Zhang Hui , Zhu Yu‐Jun , Fan Ye‐Yang , Huang Ting‐Xu , Zhang Jian‐Fu , Xie Hua‐An , Zhuang Jie‐Yun 
Published: May 2019

AbstractThis study was conducted to identify new quantitative trait loci (QTLs) that have stable effects for eating and cooking quality (ECQ) of rice. Three recombinant inbred line populations of indica rice were each planted in two years. Three traits for ECQ, amylose content (AC), gel consistency (GC) and alkali spreading value (ASV), were measured for QTL analysis. A total of 13 QTLs were detected, including four for AC, six for ASV and three for GC. Two QTLs, qGC4 in the interval RM16252–RM335 on the short arm of chromosome 4 and qGC6.2 in the Alk region, were validated in a population derived from a residual heterozygote that was homozygous at the major locus Wx. In the absence of segregation at the Wx locus, qGC4 and qGC6.2 had additive effects of 2.46 and 8.18 mm, respectively, offering a potential for improving GC property of rice varieties. Comparison between qGC4 and previous results suggests that qGC4 is likely a new QTL for GC, providing a candidate for gene cloning and functional characterization.
Motivations, success, and cost of coral reef restoration
Authors: Bayraktarov Elisa , Stewart‐Sinclair Phoebe J. , Brisbane Shantala , Boström‐Einarsson Lisa , Saunders Megan I. , Lovelock Catherine E. , Possingham Hugh P. , Mumby Peter J. , Wilson Kerrie A. 
Published: May 2019

Coral reef restoration is an increasingly important part of tropical marine conservation. Information about what motivates coral reef restoration as well as its success and cost is not well understood but is needed to inform restoration decisions. We systematically review and synthesize data from mostly scientific studies published in peer‐reviewed and gray literature on the motivations for coral reef restoration, the variables measured, outcomes reported, the cost per hectare of the restoration project, the survival of restored corals, the duration of the project, and its overall spatial extent depending on the restoration technique employed. The main motivation to restore coral reefs for the projects assessed was to further our ecological knowledge and improve restoration techniques, with coral growth, productivity, and survival being the main variables measured. The median project cost was 400,000 US$/ha (2010 US$), ranging from 6,000 US$/ha for the nursery phase of coral gardening to 4,000,000 US$/ha for substrate addition to build an artificial reef. Restoration projects were mostly of short duration (1–2 years) and over small spatial extents (0.01 ha or 108 m2). Median reported survival of restored corals was 60.9%. Future research to survey practitioners who do not publish their discoveries would complement this work. Our findings and database provide critical data to inform future research in coral reef restoration.
Sustained exercise programs for hemodialysis patients: The characteristics of successful approaches in Portugal, Canada, Mexico, and Germany
Authors: Viana João L. , Martins Pedro , Parker Kristen , Madero Magdalena , Pérez Grovas Héctor , Anding Kirsten , Degenhardt Stefan , Gabrys Iwona , Raugust Shauna , West Christina , Cowan Theresa E. , Wilund Kenneth R. 
Published: May 2019

AbstractDespite having good intentions, hemodialysis (HD) clinics often fail to sustain exercise programs that they initiate. There are many reasons for this, including a lack of funding, inadequate training of the clinic staff, a lack of exercise professionals to manage the program or train the staff, and the many challenges inherent to exercising a patient population with multiple comorbid diseases. Despite these barriers, there are several outstanding examples of successful exercise programs in HD clinics throughout the world. The aim of this manuscript is to review the characteristics of four successfully sustained HD exercise programs in Portugal, Canada, Mexico, and Germany. We describe the unique approaches they have used to fund and manage their programs, the varied exercise prescriptions they incorporate, the unique challenges they face, and discuss the benefits they have seen. While the programs differ in many regards, a consistent theme is that they each have substantial and committed support from the entire clinic staff, including the nephrologists, administration, nurses, dietitians, and technicians. This suggests that exercise programs in HD clinics can be successfully implemented and sustained provided significant effort is made to foster a culture of physical activity throughout the clinic.
Expanding Social Science Through Disaster Studies
Authors: Reinhardt Gina Yannitell , Ross Ashley D. 
Published: May 2019

ObjectivesThis article provides an overview of how the interdisciplinary field of disaster studies contributes to the social sciences.MethodsThe following themes are explored in relation to the articles contained in the special issue: disasters are social and political phenomena that generate policy change, disasters reflect and affect democratic governance, and disasters reveal shared experience and collective identity.ResultsDisaster studies bridge the social sciences theoretically and methodologically. Given the scope of disaster impacts—across social, political, economic, ecological, and infrastructure spheres—and the policy response they garner involving public, private, and civic actors, they offer a lens by which to see society and politics in a way that no other critical events can.ConclusionDisaster studies offer important applications of social science theories and concepts that expand the field, broaden our reach as social scientists, and deepen our understanding of fundamental social processes and behaviors in meaningful ways.
Corrosion of concrete pipes in a sewer environment – two case studies
Authors: Oualit Mehena , Jauberthie Raoul 
Published: May 2019

AbstractThe deterioration and cost‐effective maintenance of infrastructure has for many years been an area of social and financial importance. The deterioration of the wastewater infrastructure is particularly important because of its key role in the maintenance of public health for urban conglomerations. This paper describes two case studies that are taken from an ongoing study of the sewerage network in the Municipality of Rennes, France. Both studies concern spun concrete pipes laid approximately 55 years ago. The first case is that of a sewer in good order because of its location within the network and its design. The second case describes a sewer that has been oversized and the conditions within the reach of the sewer have led to sulphide attack. It is concluded that two important considerations that must be taken into account is the design detailing and appropriate selection of materials.
NaV1.6 regulates excitability of mechanosensitive sensory neurons
Authors: Israel Mathilde R. , Tanaka Brian S. , Castro Joel , Thongyoo Panumart , Robinson Samuel D. , Zhao Peng , Deuis Jennifer R. , Craik David J. , Durek Thomas , Brierley Stuart M. , Waxman Stephen G , Dib‐Hajj Sulayman D. , Vetter Irina 
Published: May 2019

Key points
Voltage‐gated sodium channels are critical for peripheral sensory neuron transduction and have been implicated in a number of painful and painless disorders.
The β‐scorpion toxin, Cn2, is selective for NaV1.6 in dorsal root ganglion neurons.
NaV1.6 plays an essential role in peripheral sensory neurons, specifically at the distal terminals of mechanosensing fibres innervating the skin and colon.
NaV1.6 activation also leads to enhanced response to mechanical stimulus in vivo.
This works highlights the use of toxins in elucidating pain pathways moreover the importance of non‐peripherally restricted NaV isoforms in pain generation.
AbstractPeripheral sensory neurons express multiple voltage‐gated sodium channels (NaV) critical for the initiation and propagation of action potentials and transmission of sensory input. Three pore‐forming sodium channel isoforms are primarily expressed in the peripheral nervous system (PNS): NaV1.7, NaV1.8 and NaV1.9. These sodium channels have been implicated in painful and painless channelopathies and there has been intense interest in them as potential therapeutic targets in human pain. Emerging evidence suggests NaV1.6 channels are an important isoform in pain sensing. This study aimed to assess, using pharmacological approaches, the function of NaV1.6 channels in peripheral sensory neurons. The potent and NaV1.6 selective β‐scorpion toxin Cn2 was used to assess the effect of NaV1.6 channel activation in the PNS. The multidisciplinary approach included Ca2+ imaging, whole‐cell patch‐clamp recordings, skin–nerve and gut–nerve preparations and in vivo behavioural assessment of pain. Cn2 facilitates NaV1.6 early channel opening, and increased persistent and resurgent currents in large‐diameter dorsal root ganglion (DRG) neurons. This promotes enhanced excitatory drive and tonic action potential firing in these neurons. In addition, NaV1.6 channel activation in the skin and gut leads to increased response to mechanical stimuli. Finally, intra‐plantar injection of Cn2 causes mechanical but not thermal allodynia. This study confirms selectivity of Cn2 on NaV1.6 channels in sensory neurons. Activation of NaV1.6 channels, in terminals of the skin and viscera, leads to profound changes in neuronal responses to mechanical stimuli. In conclusion, sensory neurons expressing NaV1.6 are important for the transduction of mechanical information in sensory afferents innervating the skin and viscera.
The role of community health workers in cervical cancer screening in low-income and middle-income countries: a systematic scoping review of the literature
Authors: O’Donovan James , O’Donovan Charles , Nagraj Shobhana 
Published: May 2019

IntroductionCommunity-based screening for cervical cancer and task sharing to community health workers (CHWs) have been suggested as a potential way to increase screening coverage in low- and middle-income countries (LMICs). The aims of the scoping review were to understand the following: (i) where and how CHWs are currently deployed in screening in LMIC settings; (ii) the methods used to train and support CHWs in screening, and (iii) The evidence on the cost-effectiveness of using CHWs to assist in screening.MethodsA scoping literature search of 11 major databases and the grey literature was performed between 1978 and 2018. We included comprehensive search terms for ‘CHWs’ and ‘Cervical Cancer’, and used the World Bank criteria to define LMICs.ResultsOf the 420 articles screened, 15 met the inclusion criteria for review. Studies were located in Africa (n=5), Asia (n=5), and South and Central America (n=5). CHWs played a role in community education and raising awareness (n=14), conducting or assisting in cervical screening (n=5), or follow-up (n=1). 11 studies described CHW training activities. Only one study provided a formal cost analysis.ConclusionThe roles of CHWs in cervical cancer screening in LMICs have largely to date focused on education, outreach, and awareness programmes. Community-based approaches to cervical cancer screening are feasible, although the sociocultural context plays an important role in the acceptability of these interventions. Further in-depth contextually grounded studies exploring the acceptability of such interventions are required, as well as studies exploring the cost-effectiveness of involving CHWs in cervical cancer screening activities.
Impact of pretreatment with intravenous thrombolysis on reperfusion status in acute strokes treated with mechanical thrombectomy
Authors: Goyal Nitin , Tsivgoulis Georgios , Pandhi Abhi , Malhotra Konark , Krishnan Rashi , Ishfaq Muhammad F , Krishnaiah Balaji , Nickele Christopher , Inoa-Acosta Violiza , Katsanos Aristeidis H , Hoit Daniel , Elijovich Lucas , Alexandrov Andrei , Arthur Adam S 
Published: May 2019

IntroductionWe sought to evaluate the impact of pretreatment with intravenous thrombolysis (IVT) on the rate and speed of successful reperfusion (SR) in patients with emergent large vessel occlusion (ELVO) treated with mechanical thrombectomy (MT) in a high-volume tertiary care stroke center.MethodsConsecutive patients with ELVO treated with MT were evaluated. Outcomes were compared between patients who underwent combined IVT and MT (IVT+MT) and those treated with direct MT (dMT). The elapsed time between groin puncture to beginning of reperfusion (GPTBRT) and the numbers of device passes required to achieve SR were also documented.ResultsA total of 287 and 132 patients were treated with IVT+MT and dMT, respectively. The IVT+MT group had higher SR (73.8% vs 62.9%; p=0.023) and 3-month functional independence (modified Rankin Scale score 0–2;51.6% vs 38.2%; p=0.008) rates. The median GPTBRT was shorter in the IVT+MT group (48 (IQR 33–70) vs 70 (IQR 44–98) min; p<0.001). Among patients who achieved SR (n=292), the median number of required device passes was lower in the IVT+MT subgroup (1 (IQR 1–1) vs 2 (IQR 1–2); p<0.001), while the rate of patients requiring ≤2 device passes was higher (98% vs 77%; p<0.001). IVT+MT was independently related to higher odds of SR (OR 1.64; 95% CI 1.03 to 2.61; p=0.036) and shorter GPTBRT (unstandardized linear regression coefficient −20.39; 95% CI −27.56 to –13.22; p<0.001) on multivariable analyses adjusting for potential confounders. Among patients with SR, IVT+MT was independently associated with a higher likelihood of ≤2 device passes (OR 14.63; 95% CI 4.46 to 48.00; p<0.001).ConclusionsIVT pretreatment appears to increase the rates of SR and shortens the duration of the endovascular procedure by requiring fewer device passes in patients with ELVO treated with MT.
Multicenter Phase I Study of Erdafitinib (JNJ-42756493), Oral Pan-Fibroblast Growth Factor Receptor Inhibitor, in Patients with Advanced or Refractory Solid Tumors
Authors: Bahleda Rastislav , Italiano Antoine , Hierro Cinta , Mita Alain , Cervantes Andres , Chan Nancy , Awad Mark , Calvo Emiliano , Moreno Victor , Govindan Ramaswamy , Spira Alexander , Gonzalez Martha , Zhong Bob , Santiago-Walker Ademi , Poggesi Italo , Parekh Trilok , Xie Hong , Infante Jeffrey , Tabernero Josep 
Published: May 2019

AbstractPurpose:Here, we report results of the first phase I study of erdafitinib, a potent, oral pan-FGFR inhibitor.Patients and Methods:Patients age ≥18 years with advanced solid tumors for which standard antineoplastic therapy was no longer effective were enrolled (NCT01703481). Parts 2 to 4 employed molecular screening for activating FGFR genomic alterations. In patients with such alterations, two selected doses/schedules identified during part 1 dose-escalation [9 mg once daily and 10 mg intermittently (7 days on/7 days off), as previously published (Tabernero JCO 2015;33:3401-8)] were tested.Results:The study included 187 patients. The most common treatment-related adverse events were hyperphosphatemia (64%), dry mouth (42%), and asthenia (28%), generally grade 1/2 severity. All cases of hyperphosphatemia were grade 1/2 except for 1 grade 3 event. Skin, nail, and eye changes were observed in 43%, 33%, and 28% of patients, respectively (mostly grade 1/2 and reversible after temporary dosing interruption). Urothelial carcinoma and cholangiocarcinoma were most responsive to erdafitinib, with objective response rates (ORR) of 46.2% (12/26) and 27.3% (3/11), respectively, in response-evaluable patients with FGFR mutations or fusions. All patients with urothelial carcinoma and cholangiocarcinoma who responded to erdafitinib carried FGFR mutations or fusions. Median response duration was 5.6 months for urothelial carcinoma and 11.4 months for cholangiocarcinoma. ORRs in other tumor types were &lt;10%.Conclusions:Erdafitinib shows tolerability and preliminary clinical activity in advanced solid tumors with genomic changes in the FGFR pathway, at two different dosing schedules and with particularly encouraging responses in urothelial carcinoma and cholangiocarcinoma.
HIF Inactivation of p53 in Ovarian Cancer Can Be Reversed by Topotecan, Restoring Cisplatin and Paclitaxel Sensitivity
Authors: Parmakhtiar Basmina , Burger Robert A. , Kim Jai-Hyun , Fruehauf John P. 
Published: May 2019

Abstract

Ovarian cancer growth under hypoxic conditions results in hypoxia-inducible factor-1α (HIF1α) stabilization. HIF1α is an adverse prognostic factor that may contribute to worse outcomes via its capacity to bind to p53, potentially blocking p53-mediated apoptosis. We determined whether HIF1α-p53 binding occurred in hypoxic ovarian cancer cell lines, and if this blocked p53 transcriptional activity. Topotecan (TPT), used in the treatment of ovarian cancer, inhibits HIF1α translation via a topoisomerase-1 (TOPO1)–dependent mechanism. We examined if TPT knockdown of HIF1α restored p53 transcriptional function. TPT effects on HIF1α and p53-related transcriptional targets were assessed by PCR. Associations between TPT effects and TOPO1 expression levels were examined by Western blots and knockdown by siRNA. RNA-binding protein immunoprecipitation was used to assess if TOPO1 was resident on HIF1α mRNA. We determined if sublethal doses of TPT, used to knockdown HIF1α, reversed hypoxia-related cisplatin and paclitaxel resistance (XTT assay). Flow cytometry was used to assess HIF1α-mediated upregulation of ABCB1 and ABCB5 efflux pump expression. We found that HIF1α binding to, and inhibition of, p53 transcriptional activity in hypoxic ovarian cancer cells was associated with drug resistance. TPT-mediated downregulation of HIF1α in hypoxic cells required TOPO1 resident on HIF1α mRNA, restored p53 transcriptional activity, downregulated ABCB1/ABCB5 cell surface expression, and reversed hypoxia-related cisplatin and paclitaxel resistance.

Implications:
TPT-mediated reduction of HIF1α accumulation in hypoxic ovarian cancer cell lines restores p53 tumor-suppressor function, offering a novel approach to reverse chemoresistance. Further clinical investigation is warranted.
The Codon 72 TP53 Polymorphism Contributes to TSC Tumorigenesis through the Notch–Nodal Axis
Authors: Cho Jun-Hung , Patel Bhaumik , Bonala Santosh , Mansouri Hossein , Manne Sasikanth , Vadrevu Surya Kumari , Ghouse Shanawaz , Kung Che-Pei , Murphy Maureen E. , Astrinidis Aristotelis , Henske Elizabeth P. , Kwiatkowski David J. , Markiewski Maciej M. , Karbowniczek Magdalena 
Published: May 2019

Abstract

We discovered that 90.3% of patients with angiomyolipomas, lymphangioleiomyomatosis (LAM), and tuberous sclerosis complex (TSC) carry the arginine variant of codon 72 (R72) of TP53 and that R72 increases the risk for angiomyolipoma. R72 transactivates NOTCH1 and NODAL better than the proline variant of codon 72 (P72); therefore, the expression of NOTCH1 and NODAL is increased in angiomyolipoma cells that carry R72. The loss of Tp53 and Tsc1 within nestin-expressing cells in mice resulted in the development of renal cell carcinomas (RCC) with high Notch1 and Nodal expression, suggesting that similar downstream mechanisms contribute to tumorigenesis as a result of p53 loss in mice and p53 polymorphism in humans. The loss of murine Tp53 or expression of human R72 contributes to tumorigenesis via enhancing epithelial-to-mesenchymal transition and motility of tumor cells through the Notch and Nodal pathways.

Implications:
This work revealed unexpected contributions of the p53 polymorphism to the pathogenesis of TSC and established signaling alterations caused by this polymorphism as a target for therapy. We found that the codon 72 TP53 polymorphism contributes to TSC-associated tumorigenesis via Notch and Nodal signaling.