bluuebunny/crossref_metadata_2025 huggingface dataset:
Relationship of Leaf Surface Characteristics to Acifluorfen Tolerance in Tomato (Lycopersicon esculentum) and Related Species
Authors: Ricotta Jacqueline A. , Masiunas John B.
Published: May 2019

Fourteen tomato genotypes, eastern black nightshade, and 35Lycopersiconaccessions were screened for tolerance to acifluorfen. Tolerant and susceptible genotypes occurred in most species. Fifteen genotypes were chosen for further study depending on their fresh weight after acifluorfen treatment Over all 15 genotypes, there was no correlation between trichome density and acifluorfen tolerance; however, inL. esculentum, cultivars with the most trichomes were the most tolerant There was an inverse relationship between stomata density and tolerance. Amount and composition of epicuticular wax and cuticle thickness did not correlate to acifluorfen tolerance.
Factors Influencing Shattercane (Sorghum bicolor) Seed Survival
Authors: Fellows Gary M. , Roeth Fred W.
Published: May 2019

Shattercane seed survival during soil burial was highly dependent on attached glumes. Shattercane seed tightly enclosed by glumes averaged 5 and 53% germination after 4 mo of winter burial in 1988 and 1989, respectively. Shattercane caryopses (seed without glumes) survival averaged 0.5 and 17% compared to 17 and 41% when treated with seed fungicides in 1988 and 1989, respectively. Shattercane caryopses tannin and lignin contents were higher than for cultivated sorghum caryopses. Glume tannin was four times higher and glume lignin was five times higher than in the caryopsis. Shattercane seed survival was positively correlated with glume tightness, caryopsis lignin, and glume tannin. Tannin and lignin appear to function as barriers to microbial invasion resulting in higher shattercane seed resistance to overwinter demise. Attempts to isolate fungal inhibitors from shattercane seed were unsuccessful.
Stimulation of Germination of Seeds of Cowpea Witchweed (Striga gesnerioides) by Sodium Hypochlorite and Some Growth Regulators
Authors: Igbinnosa I. , Okonkwo S.N.C.
Published: May 2019

Tests with 18 growth regulators and chemicals revealed that the cytokinins [zeatin, kinetin, and 6-benzylaminopurine (BAP)], ethylene, and sodium hypochlorite stimulate germination of cowpea witchweed seeds at various concentrations. Witchweed seeds preconditioned in different concentrations of sodium hypochlorite for 3 wk had germination rates of 25 to 89% after incubation in distilled water, 10−5M solution of kinetin, 50 mg L−1of 2-chloroethylphosphonic acid, and exudates from cowpea roots. Witchweed seeds preconditioned in distilled water and subsequently incubated in distilled water did not germinate.
Gibberellin Synthesis Inhibitor Effects on Submersed Aquatic Weed Species
Authors: Netherland Michael D. , Lembi Carole A.
Published: May 2019

A laboratory bioassay showed that inhibitors of gibberellin synthesis (flurprimidol, paclobutrazol, and uniconazole) reduced plant height but did not affect physiological parameters such as photosynthesis, respiration, and chlorophyll content in two weedy submersed aquatic plants, hydrilla and Eurasian watermilfoil. Eurasian watermilfoil was sensitive to these compounds at concentrations as low as 0.75 μg L−1. Hydrilla sensitivity was in the range of 75 to 750 μg L−1. The three compounds reduced main and lateral stem lengths in hydrilla; however, at 75 μg L−1the number of lateral stems and roots was greatly increased over untreated controls resulting in a stoloniferous growth habit. Dominant growth form of treated Eurasian watermilfoil was a single shortened stem with numerous compacted buds. Photosynthesis, respiration, and chlorophyll content were not affected in either plant at nontoxic dosages in which stem reduction was obtained. Both plants required only a 24-h exposure to maintain main stem length reduction for 6 wk after transfer to untreated medium. Our results indicate that these gibberellin synthesis inhibitors would be effective in reducing plant height in aquatic systems.
Germination ofSicyos deppei(Cucurbitaceae) Seeds as Affected by Scarification and Light
Authors: Brechu-Franco Alicia , Cruz-Garcia Felipe , Marquez-Guzman Judith , Laguna-Hernandez Guillermo
Published: May 2019

Sicyos deppeiG. Don (Cucurbitaceae) is an annual weed that disperses dormant seeds. The influence of scarification and light on their germination was studied in the laboratory. Scarified seeds collected in 1987, 6, 7, 8, and 9 mo postharvest, gave high germination both in white light (89 to 100%) and darkness (64 to 96%), in comparison with nonscarified seeds which germinated 7 to 20% in both conditions. Scarified seeds collected in 1989, 3 mo postharvest, germinated higher (52 to 69%) than nonscarified seeds (0 to 5%). Exposure to light did not break dormancy of nonscarified seeds. The reversal of dormancy by scarification describes them as hard seeds. Scarified seeds, 3 mo postharvest, were light indifferent, germinating even in the usually inhibitory condition of far-red light. However, a low proportion of scarified seeds, 6 and 7 mo postharvest, presented a positive photoblastic response and germinated 23 and 36%, respectively.
Comparison of Restriction Fragment Length Polymorphisms in Chloroplast DNA of Five Leafy Spurge (Euphorbiaspp.) Accessions
Authors: Nissen Scott J. , Masters Robert A. , Lee Donald J. , Rowe Martha L.
Published: May 2019

Chloroplast DNA (cpDNA) restriction fragment length polymorphisms (RFLPs) were analyzed to assess genetic variation and relatedness among selections of North American and Eurasian leafy spurge. Leafy spurge accessions from Nebraska, Montana, Russia, Italy, and Austria were evaluated. Total DNA was extracted from young leaves and digested with the restriction endonuclease,EcoRI. CpDNA fragment patterns were determined by Southern blot analysis using mung bean cpDNA probes. Colinearity between the mung bean and leafy spurge chloroplast genomes was indicated by the observation that common fragments were hybridized by adjacent probes. Minimum estimates of chloroplast genome size for the five leafy spurge accessions, which ranged in kilobase size from 130 to 132, were within the size range of most terrestrial plants. Structural collinearity and reasonable estimates of chloroplast genome size provided evidence that the mung bean cpDNA library was suitable for characterizing leafy spurge cpDNA. Seven of the 13 mung bean probes hybridized to polymorphic leafy spurge cpDNA fragments. Based on number of polymorphisms unique to each Eurasian accession, the Austrian accession appeared to be most divergent followed by the Italian and Russian. The North American accessions seem to be most closely related to each other and to the Russian leafy spurge accession.
Prediction of Black and Eastern Black Nightshade (Solanum nigrumand S.ptycanthum) Growth Using Degree-Days
Authors: McGiffen Milton E. , Masiunas John B.
Published: May 2019

The objectives were to compare the growth of black and eastern black nightshade and develop predictive models for their growth. Black and eastern black nightshade were planted on June 3 and 23, and July 12 in 1988 and May 28, June 17, and July 10 in 1989. Exponential models were strongly correlated with the growth of both species across all planting dates. Eastern black nightshade produced more biomass than black nightshade, although weight of berries was equivalent. Leaf area per plant 60 d after planting was five times greater for eastern black nightshade than black nightshade. Eastern black nightshade responded to self-shading by increasing specific leaf area.
I MONDI DEL BENESSERE: UNA NUOVA CLASSIFICAZIONE DEI WELFARE STATES
Authors: Ferrera Maurizio
Published: May 2019

Introduzione

Nel corso dell'ultimo decennio la ricerca comparata sul welfare state ha progressivamente abbandonato l'approccio quantitativo, imperniato sul trattamento statistico di dati aggregati, per indirizzarsi con sempre maggiore convinzione verso l'analisi qualitativa, volta all'esplorazione ravvicinata di singole (o gruppi di) esperienze nazionali concrete, osservate nella loro evoluzione storica. La letteratura metodologica ha parlato in proposito di un ri-orientamento da una strategia «a intensità di variabili» (ovariable-centred) a una strategia «a intensità di casi» (ocase-centred), ovvero da una logica di spiegazione basata sulle «generalizzazioni trans-storiche», di matrice durkheimiana ad una basata sulle «generalizzazioni storiche», di matrice weberiana. Anche se ancora agli inizi, il nuovo filone qualitativo ha già apportato nuovi e importanti contributi conoscitivi sull'evoluzione del welfare state occidentale e sulle principali diversità di percorso osservabili tra paesi. Tuttavia il potenziale euristico di questi contributi è rimasto spesso limitato da un'insufficiente messa a punto degli strumenti concettuali e classificatori da essi utilizzati.
L'IDENTITÀ DELLA SINISTRA: LE POLITICHE SOCIALDEMOCRATICHE NELL'EUROPA DEL SUD
Authors: Maravall José Maria
Published: May 2019

Introduzione

Questo articolo intende discutere i programmi e le politiche realizzate dai partiti socialisti dell'Europa del Sud giunti al potere negli anni ottanta. Vi sono considerati i partiti socialisti spagnolo (PSOE), greco (PASOK), portoghese (PSP), italiano (PSI) e francese (PS). Per i primi tre, la democrazia costituiva un'esperienza recente, esito delle transizioni dall'autoritarismo della metà degli anni settanta; negli altri due casi, era stata invece ristabilita al termine del secondo conflitto mondiale. Tre dei partiti socialisti considerati – PSOE, PS e PASOK – giungevano al potere forti di maggioranze assolute al Parlamento e dopo una lunga esclusione dal potere. Al contrario, i partiti socialisti portoghese e italiano facevano parte di coalizioni, con l'eccezione, in Portogallo, di un breve periodo di governo monopartitico socialista, dalle elezioni del 1976 fino alla fine del 1977. Il PSI, inoltre, figura al governo come partner minore, sebbene Craxi sia stato primo ministro dal 1983 al 1987. L'analisi comparata delle politiche sarà quindi agéométrie variable: poiché la presenza di coalizioni rende difficile assumere il bilancio dell'azione del governo come indicativo di specifiche politiche socialiste, il lavoro discuterà i casi di Spagna, Francia e Grecia con maggior dovizia.
A Rationale for Dopamine Agonists as Primary Therapy for Parkinson’s Disease
Authors: Olanow C.W.
Published: May 2019

Levodopa is the most potent symptomatic treatment for Parkinson’s disease but adverse reactions are common and the initial response is not maintained. Further there is recent evidence that suggests that free radicals generated from the oxidative metabolism of dopamine may contribute to the pathogenesis of Parkinson’s disease. This raises the possibility that levodopa therapy by way of its conversion to dopamine may promote free radical formation and accelerate the rate of neuronal damage. Levodopa sparing strategies designed to minimize the cumulative levodopa dosage employed over the course of the disease seem a rational way to treat Parkinson patients in face of current information. Such a strategy would include the use of dopamine agonists as primary symptomatic therapy, the introduction of levodopa as an adjunct when dopamine agonists can no longer sufficiently provide satisfactory clinical control and the use of the lowest dose of levodopa that will provide satisfactory clinical control. In this way symptomatic control is not compromised on theoretical grounds, but the cumulative levodopa dose is minimized in an effort to reduce the likelihood of free radical formation with their potential adverse consequences on disease progression.
Suppression of Spreading Depression of Leão in Neocortex by an N-Methyl-D-Aspartate Receptor Antagonist
Authors: McLachlan Richard S.
Published: May 2019

Spreading depression has been implicated in the pathophysiology of a number of diseases such as migraine, stroke and epilepsy. The characteristics of this phenomenon were explored in neocortex of anesthetized rats. Spreading depression was produced in 10 of 15 animals using mechanical, electrical and chemical stimulation. Mean amplitude of the DC shift was -9.3 mV, mean duration at any one electrode 65 sec and rate of spread 2-5 mm/min. Spreading depression was facilitated by focal interictal spike activity induced by penicillin and completely blocked by the N-methyl-D-aspartate (NMDA) receptor antagonist, DL-2-aminophosphonovaleric acid (APV), providing further evidence that excitatory amino acid neurotransmission is a critical element in the development or propagation of the phenomenon.
Malignant Astrocytoma of the Optic Nerve in a Child
Authors: Safneck Janice R. , Napier Lee B. , Halliday William C.
Published: May 2019

Malignant gliomas of optic nerve and chiasm are rare, rapidly fatal neoplasms of adulthood. This report documents the occurrence of a malignant astrocytoma of the optic nerve in an 11-year-old boy who 9 years previously had a cerebellar medulloblastoma treated with surgery and irradiation. This malignant optic nerve glioma followed the same aggressive clinical course as that seen in adults, with death 9 months after diagnosis despite surgery and chemotherapy: Radiation may have been an important factor in the development of this malignant tumor which is almost never seen in the pediatric age group.
Amyotrophic Lateral Sclerosis: Interleukin-6 Levels in Cerebrospinal Fluid
Authors: Krieger Charles , Perry Thomas L. , Ziltener Hermann J.
Published: May 2019

Recent observations indicate that antibodies to gangliosides are found in many patients with amyotrophic lateral sclerosis (ALS). If antigen-antibody complexes occur in ALS, elevations of cytokine levels might be expected, among them the cytokine interleukin-6 (IL-6). IL-6 is secreted by activated monocytes and other cell types and is an important mediator of the inflammatory response. We have measured cerebrospinal fluid (CSF) IL-6 levels in patients with ALS and compared them with those in psychiatric and neurodegenerative disorders not believed to be due to immune disorders of the central nervous system. We found no significant differences in CSF IL-6 levels between these groups.
Treatment of Acquired Autoimmune Myasthenia Gravis: a Topic Review
Authors: Verma Pradeep , Oger Joël
Published: May 2019

We propose a new approach to staging the disease based on clinical and immunological response to treatment. We oppose clinical remission to immunological remission and define total clinical remission as the goal of therapy. We describe the use, side effects and indications of established therapies. Acetycholine esterase inhibitors are only a symptomatic treatment as is plasma exchange. Usefulness and limits of thymectomy, corticosteroids and immunosuppressants are described here. Their goal is to reduce the auto-immune process. Long-term hazards from these medications are described and methods to reduce their potential risks are suggested. We suggest the number of patients having life threatening complications while undergoing aggressive immunosuppression can be reduced by a systematic approach to follow-up. In the second part of this review article, adapting management to specific situations is emphasized in refractory disease, respiratory failure, neonatal and juvenile forms of the disease. The special situation of seronegative myasthenia is discussed.
MRI Diagnosis of Brainstem Cavernous Angiomas Presenting as Tumours
Authors: Preul Mark C. , Villemure Jean-Guy , Leblanc Richard , del Carpio-O’Donovan Raquel
Published: May 2019

We report experience with 11 patients misdiagnosed for years, on the basis of computed tomography (CT) and angiography, as harbouring brainstem tumours in whom magnetic resonance imaging (MRI) demonstrated cavernous angiomas. Seven had undergone external irradiation, 2 had a ventriculo-peritoneal shunt, 2 developed aseptic femur necrosis following corticosteroid treatment, 1 had undergone a biopsy with a pathological diagnosis of glioma. CT had depicted ill-defined, hyperdense, faintly enhancing lesions. Angiography was normal, or showed an avascular mass or subtle venous pooling. MRI delineated discrete lesions, typical of cavernous angiomas, with a mixed hyperintense, reticulated, central core surrounded by a hypointense rim. Six patients subsequently underwent stereotactic radiosurgery without changes in clinical status or lesion. Although hemorrhagic neoplasms may mimic the clinical course and MRI appearance of cavernous angiomas, MRI is useful in the diagnosis of brainstem cavernous angiomas and should be performed in patients with suspected brainstem tumours.
Spontaneous Disappearance of an Intracranial Aneurysm After Subarachnoid Hemorrhage
Authors: Hamilton Mark G. , Dold Oliver N.R.
Published: May 2019

Spontaneous disappearance of an intracranial aneurysm after subarachnoid hemorrhage is an uncommon event and usually associated with severe cerebral vasospasm, giant aneurysms or the use of antifibrinolytics. We present a young woman who suffered a grade 5 subarachnoid hemorrhage with severe vasospasm caused by a small anterior communicating artery aneurysm. The patient underwent a slow recovery and two years later requested surgery. Angiography demonstrated complete disappearance of the aneurysm. The neurosurgeon should be aware that spontaneous thrombosis of cerebral aneurysms can occur and ensure that angiography is repeated when surgery is significantly delayed.
The Anticonvulsant Effects of Vitamin E: A Further Evaluation
Authors: Levy Sheldon L. , Burnham W.M. , Bishai A. , Hwang Paul A.
Published: May 2019

Vitamin E (d-α-tocopherol) has proven to be a useful adjunct to anticonvulsant drugs in clinical studies. Improvement has occurred even in patients with complex partial seizures, which are often resistant to drug therapy. In animals, vitamin E is effective against ferrous chloride seizures, hyperbaric oxygen seizures and penicillin-induced seizures. It has failed, however, to show anticonvulsant effects in the standard animal models used for drug screening – the maximal electroshock and threshold pentylenetetrazol tests. The present experiments were designed to further explore the anti-epileptic actions of vitamin E in animals. Three models related to complex partial epilepsy were used: 1) the development of amygdala-kindled seizures; 2) the development of electrically-induced status in kindled animals; and 3) the development of kainic-acid seizures. Vitamin E failed to produce significant effects in any of the models.
Neuroblastoma and Fetal Exposure to Phenytoin in a Child Without Dysmorphic Features
Authors: Al-Shammri S. , Guberman A. , Hsu E.
Published: May 2019

Despite the fact that the teratogenic effects of phenytoin have been suggested in several case reports, the evidence for a possible oncogenic potential of phenytoin has not been widely recognized. Recently, neuroblastoma as well as other neuroectodermal and non-ectodermal tumors has been seen in several children exposed to phenytoin prenatally. Previous cases have been almost uniformly associated with the features of “fetal hydantoin syndrome” and none have been developmentally normal. We report a developmentally-normal boy of 2½ years with an abdominal neuroblastoma whose mother had been on phenytoin (as well as carbamazepine) throughout gestation. We review the various neoplasms which have been reported in the offspring of mothers receiving phenytoin.
Field Trials as an Extension Technique: The Case of Swaziland
Authors: Abler David G. , Rauniyar Ganesh P. , Goode Frank M.
Published: May 2019

One potentially serious problem in evaluating the effectiveness of extension programs is that participants are not picked at random. Self-selection can be a problem, and it can be compounded if extension officials concentrate on the most progressive farms. This study explores the relationships between adoption of maize high-yielding varieties (HYVs) and participation in field trials intended to foster HYV usage, drawing on data from Swaziland. Results indicate that it is impossible to say if field trials had any effect on adoption. Participating farms used more HYVs, but this could have been due to self-selection or the government's selection process.
Standard v. baby-led complementary feeding: a comparison of food and nutrient intakes in 6–12-month-old infants in the UK
Authors: Alpers Brigid , Blackwell Victoria , Clegg Miriam E
Published: May 2019

Objective:

To compare food and nutrient intakes of infants aged 6–12 months following a baby-led complementary feeding (BLCF) approach and a standard weaning (SW) approach.

Design:

Participants completed an online questionnaire consisting of sociodemographic questions, a 28 d FFQ and a 24 h dietary recall.

Setting:

UK.

Participants:

Infants (n 134) aged 6–12 months (n 88, BLCF; n 46, SW).

Results:

There was no difference between weaning methods for the food groups ‘fruits’, ‘vegetables’, ‘all fish’, ‘meat and fish’, ‘sugary’ or ‘starchy’ foods. The SW group was offered ‘fortified infant cereals’ (P < 0·001), ‘salty snacks’ at 6–8 months (P = 0·03), ‘dairy and dairy-based desserts’ at 9–12 months (P = 0·04) and ‘pre-prepared baby foods’ at all ages (P < 0·001) more often than the BLCF group. The SW group was offered ‘oily fish’ at all ages (P < 0·001) and 6–8 months (P = 0·01) and ‘processed meats’ at all ages (P < 0·001), 6–8 months (P = 0·003) and 9–12 months (P < 0·001) less often than the BLCF group. The BLCF group had significantly greater intakes of Na (P = 0·028) and fat from food (P = 0·035), and significantly lower intakes of Fe from milk (P = 0·012) and free sugar in the 6–8 months subgroup (P = 0·03) v. the SW group. Fe intake was below the Reference Nutrient Intake (RNI) for both groups and Na was above the RNI in the BLCF group.

Conclusion:

Compared with the SW group, the BLCF group was offered foods higher in Na and lower in Fe; however, the foods offered contained less free sugar.
Combination of 5-fluorouracil and thymoquinone targets stem cell gene signature in colorectal cancer cells
Authors: Ndreshkjana Benardina , Çapci Aysun , Klein Volker , Chanvorachote Pithi , Muenzner Julienne K. , Huebner Kerstin , Steinmann Sara , Erlenbach-Wuensch Katharina , Geppert Carol I. , Agaimy Abbas , Ballout Farah , El-Baba Chirine , Gali-Muhtasib Hala , Roehe Adriana Vial , Hartmann Arndt , Tsogoeva Svetlana B. , Schneider-Stock Regine
Published: May 2019

Cancer stem cells (CSCs) residing in colorectal cancer tissues have tumorigenic capacity and contribute to chemotherapeutic resistance and disease relapse. It is well known that the survival of colorectal CSCs after 5-fluorouracil (5-FU)-based therapy leads to cancer recurrence. Thus CSCs represent a promising drug target. Here, we designed and synthesized novel hybrid molecules linking 5-FU with the plant-derived compound thymoquinone (TQ) and tested the potential of individual compounds and their combination to eliminate colorectal CSCs. Both, Combi and SARB hybrid showed augmented cytotoxicity against colorectal cancer cells, but were non-toxic to organoids prepared from healthy murine small intestine. NanoString analysis revealed a unique signature of deregulated gene expression in response to the combination of TQ and 5-FU (Combi) and SARB treatment. Importantly, two principle stem cell regulatory pathways WNT/ß-Catenin and PI3K/AKT were found to be downregulated after Combi and hybrid treatment. Furthermore, both treatments strikingly eliminated CD133+ CSC population, accompanying the depleted self-renewal capacity by eradicating long-term propagated 3D tumor cell spheres at sub-toxic doses. In vivo xenografts on chicken eggs of SARB-treated HCT116 cells showed a prominent nuclear ß-Catenin and E-cadherin staining. This was in line with the reduced transcriptional activity of ß-Catenin and diminished cell adhesion under SARB exposure. In contrast to 5-FU, both, Combi and SARB treatment effectively reduced the angiogenic capacity of the remaining resistant tumor cells. Taken together, combination or hybridization of single compounds target simultaneously a broader spectrum of oncogenic pathways leading to an effective eradication of colorectal cancer cells.
Coulombic self-ordering upon charging a large-capacity layered cathode material for rechargeable batteries
Authors: Mortemard de Boisse Benoit , Reynaud Marine , Ma Jiangtao , Kikkawa Jun , Nishimura Shin-ichi , Casas-Cabanas Montse , Delmas Claude , Okubo Masashi , Yamada Atsuo
Published: May 2019

Lithium- and sodium-rich layered transition-metal oxides have recently been attracting significant interest because of their large capacity achieved by additional oxygen-redox reactions. However, layered transition-metal oxides exhibit structural degradation such as cation migration, layer exfoliation or cracks upon deep charge, which is a major obstacle to achieve higher energy-density batteries. Here we demonstrate a self-repairing phenomenon of stacking faults upon desodiation from an oxygen-redox layered oxide Na2RuO3, realizing much better reversibility of the electrode reaction. The phase transformations upon charging A2MO3 (A: alkali metal) can be dominated by three-dimensional Coulombic attractive interactions driven by the existence of ordered alkali-metal vacancies, leading to counterintuitive self-repairing of stacking faults and progressive ordering upon charging. The cooperatively ordered vacancy in lithium-/sodium-rich layered transition-metal oxides is shown to play an essential role, not only in generating the electro-active nonbonding 2p orbital of neighbouring oxygen but also in stabilizing the phase transformation for highly reversible oxygen-redox reactions.
A high-throughput screen indicates gemcitabine and JAK inhibitors may be useful for treating pediatric AML
Authors: Drenberg Christina D. , Shelat Anang , Dang Jinjun , Cotton Anitria , Orwick Shelley J. , Li Mengyu , Jeon Jae Yoon , Fu Qiang , Buelow Daelynn R. , Pioso Marissa , Hu Shuiying , Inaba Hiroto , Ribeiro Raul C. , Rubnitz Jeffrey E. , Gruber Tanja A. , Guy R. Kiplin , Baker Sharyn D.
Published: May 2019

Improvement in survival has been achieved for children and adolescents with AML but is largely attributed to enhanced supportive care as opposed to the development of better treatment regimens. High risk subtypes continue to have poor outcomes with event free survival rates <40% despite the use of high intensity chemotherapy in combination with hematopoietic stem cell transplant. Here we combine high-throughput screening, intracellular accumulation assays, and in vivo efficacy studies to identify therapeutic strategies for pediatric AML. We report therapeutics not currently used to treat AML, gemcitabine and cabazitaxel, have broad anti-leukemic activity across subtypes and are more effective relative to the AML standard of care, cytarabine, both in vitro and in vivo. JAK inhibitors are selective for acute megakaryoblastic leukemia and significantly prolong survival in multiple preclinical models. Our approach provides advances in the development of treatment strategies for pediatric AML.
Innate lymphocyte-induced CXCR3B-mediated melanocyte apoptosis is a potential initiator of T-cell autoreactivity in vitiligo
Authors: Tulic Meri K. , Cavazza Elisa , Cheli Yann , Jacquel Arnaud , Luci Carmelo , Cardot-Leccia Nathalie , Hadhiri-Bzioueche Hanene , Abbe Patricia , Gesson Maéva , Sormani Laura , Regazzetti Claire , Beranger Guillaume E. , Lereverend Cedric , Pons Caroline , Khemis Abdallah , Ballotti Robert , Bertolotto Corine , Rocchi Stéphane , Passeron Thierry
Published: May 2019

T-cells play a crucial role in progression of autoimmunity, including vitiligo, yet the initial steps triggering their activation and tissue damage remain unknown. Here we demonstrate increased presence of type-1 innate lymphoid cells (NK and ILC1)-producing interferon gamma (IFNγ) in the blood and in non-lesional skin of vitiligo patients. Melanocytes of vitiligo patients have strong basal expression of chemokine-receptor-3 (CXCR3) isoform B which is directly regulated by IFNγ. CXCR3B activation by CXCL10 at the surface of cultured human melanocytes induces their apoptosis. The remaining melanocytes, activated by the IFNγ production, express co-stimulatory markers which trigger T-cell proliferation and subsequent anti-melanocytic immunity. Inhibiting the CXCR3B activation prevents this apoptosis and the further activation of T cells. Our results emphasize the key role of CXCR3B in apoptosis of melanocytes and identify CXCR3B as a potential target to prevent and to treat vitiligo by acting at the early stages of melanocyte destruction.
Real-time observation of X-ray-induced intramolecular and interatomic electronic decay in CH2I2
Authors: Fukuzawa Hironobu , Takanashi Tsukasa , Kukk Edwin , Motomura Koji , Wada Shin-ichi , Nagaya Kiyonobu , Ito Yuta , Nishiyama Toshiyuki , Nicolas Christophe , Kumagai Yoshiaki , Iablonskyi Denys , Mondal Subhendu , Tachibana Tetsuya , You Daehyun , Yamada Syuhei , Sakakibara Yuta , Asa Kazuki , Sato Yuhiro , Sakai Tsukasa , Matsunami Kenji , Umemoto Takayuki , Kariyazono Kango , Kajimoto Shinji , Sotome Hikaru , Johnsson Per , Schöffler Markus S. , Kastirke Gregor , Kooser Kuno , Liu Xiao-Jing , Asavei Theodor , Neagu Liviu , Molodtsov Serguei , Ochiai Kohei , Kanno Manabu , Yamazaki Kaoru , Owada Shigeki , Ogawa Kanade , Katayama Tetsuo , Togashi Tadashi , Tono Kensuke , Yabashi Makina , Ghosh Aryya , Gokhberg Kirill , Cederbaum Lorenz S. , Kuleff Alexander I. , Fukumura Hiroshi , Kishimoto Naoki , Rudenko Artem , Miron Catalin , Kono Hirohiko , Ueda Kiyoshi
Published: May 2019

The increasing availability of X-ray free-electron lasers (XFELs) has catalyzed the development of single-object structural determination and of structural dynamics tracking in real-time. Disentangling the molecular-level reactions triggered by the interaction with an XFEL pulse is a fundamental step towards developing such applications. Here we report real-time observations of XFEL-induced electronic decay via short-lived transient electronic states in the diiodomethane molecule, using a femtosecond near-infrared probe laser. We determine the lifetimes of the transient states populated during the XFEL-induced Auger cascades and find that multiply charged iodine ions are issued from short-lived (∼20 fs) transient states, whereas the singly charged ones originate from significantly longer-lived states (∼100 fs). We identify the mechanisms behind these different time scales: contrary to the short-lived transient states which relax by molecular Auger decay, the long-lived ones decay by an interatomic Coulombic decay between two iodine atoms, during the molecular fragmentation.
Ciclopirox inhibits Hepatitis B Virus secretion by blocking capsid assembly
Authors: Kang Jung-Ah , Kim Songwon , Park Minji , Park Hyun-Jin , Kim Jeong-Hyun , Park Sanghyeok , Hwang Jeong-Ryul , Kim Yong-Chul , Jun Kim Yoon , Cho Yuri , Sun Jin Mi , Park Sung-Gyoo
Published: May 2019

Chronic hepatitis B virus (HBV) infection can cause cirrhosis and hepatocellular carcinoma and is therefore a serious public health problem. Infected patients are currently treated with nucleoside/nucleotide analogs and interferon α, but this approach is not curative. Here, we screen 978 FDA-approved compounds for their ability to inhibit HBV replication in HBV-expressing HepG2.2.15 cells. We find that ciclopirox, a synthetic antifungal agent, strongly inhibits HBV replication in cells and in mice by blocking HBV capsid assembly. The crystal structure of the HBV core protein and ciclopirox complex reveals a unique binding mode at dimer-dimer interfaces. Ciclopirox synergizes with nucleoside/nucleotide analogs to prevent HBV replication in cells and in a humanized liver mouse model. Therefore, orally-administered ciclopirox may provide a novel opportunity to combat chronic HBV infection by blocking HBV capsid assembly.
TYGS is an automated high-throughput platform for state-of-the-art genome-based taxonomy
Authors: Meier-Kolthoff Jan P. , Göker Markus
Published: May 2019

Microbial taxonomy is increasingly influenced by genome-based computational methods. Yet such analyses can be complex and require expert knowledge. Here we introduce TYGS, the Type (Strain) Genome Server, a user-friendly high-throughput web server for genome-based prokaryote taxonomy, connected to a large, continuously growing database of genomic, taxonomic and nomenclatural information. It infers genome-scale phylogenies and state-of-the-art estimates for species and subspecies boundaries from user-defined and automatically determined closest type genome sequences. TYGS also provides comprehensive access to nomenclature, synonymy and associated taxonomic literature. Clinically important examples demonstrate how TYGS can yield new insights into microbial classification, such as evidence for a species-level separation of previously proposed subspecies ofSalmonella enterica. TYGS is an integrated approach for the classification of microbes that unlocks novel scientific approaches to microbiologists worldwide and is particularly helpful for the rapidly expanding field of genome-based taxonomic descriptions of new genera, species or subspecies.
Direct imaging of the circular chromosome in a live bacterium
Authors: Wu Fabai , Japaridze Aleksandre , Zheng Xuan , Wiktor Jakub , Kerssemakers Jacob W. J. , Dekker Cees
Published: May 2019

Although the physical properties of chromosomes, including their morphology, mechanics, and dynamics are crucial for their biological function, many basic questions remain unresolved. Here we directly image the circular chromosome in live E. coli with a broadened cell shape. We find that it exhibits a torus topology with, on average, a lower-density origin of replication and an ultrathin flexible string of DNA at the terminus of replication. At the single-cell level, the torus is strikingly heterogeneous, with blob-like Mbp-size domains that undergo major dynamic rearrangements, splitting and merging at a minute timescale. Our data show a domain organization underlying the chromosome structure of E. coli, where MatP proteins induce site-specific persistent domain boundaries at Ori/Ter, while transcription regulators HU and Fis induce weaker transient domain boundaries throughout the genome. These findings provide an architectural basis for the understanding of the dynamic spatial organization of bacterial genomes in live cells.
Ultrafast multi-focus 3-D nano-fabrication based on two-photon polymerization
Authors: Geng Qiang , Wang Dien , Chen Pengfei , Chen Shih-Chi
Published: May 2019

Two-photon polymerization (TPP) is the most precise 3-D printing process that has been used to create many complex structures for advanced photonic and nanoscale applications. However, to date the technology still remains a laboratory tool due to its high operation cost and limited fabrication rate, i.e., serial laser scanning process. Here we present a revolutionary laser nanofabrication process based on TPP and an ultrafast random-access digital micromirror device (DMD) scanner. By exploiting binary holography, the DMD scanner can simultaneously generate and individually control one to tens of laser foci for parallel nanofabrication at 22.7 kHz. Complex 3-D trusses and woodpile structures have been fabricated via single or multi-focus processes, showing a resolution of ~500 nm. The nanofabrication system may be used for largescale nano-prototyping or creation of complex structures, e.g., overhanging structures, that cannot be easily fabricated via conventional raster-scanning-based systems, bringing significant impact to the world of nanomanufacturing.
secCl is a cys-loop ion channel necessary for the chloride conductance that mediates hormone-induced fluid secretion in Drosophila
Authors: Feingold Daniel , Knogler Laura , Starc Tanja , Drapeau Pierre , O’Donnell Michael J. , Nilson Laura A. , Dent Joseph A.
Published: May 2019

Organisms use circulating diuretic hormones to control water balance (osmolarity), thereby avoiding dehydration and managing excretion of waste products. The hormones act through G-protein-coupled receptors to activate second messenger systems that in turn control the permeability of secretory epithelia to ions like chloride. In insects, the chloride channel mediating the effects of diuretic hormones was unknown. Surprisingly, we find a pentameric, cys-loop chloride channel, a type of channel normally associated with neurotransmission, mediating hormone-induced transepithelial chloride conductance. This discovery is important because: 1) it describes an unexpected role for pentameric receptors in the membrane permeability of secretory epithelial cells, and 2) it suggests that neurotransmitter-gated ion channels may have evolved from channels involved in secretion.
Significant plastic accumulation on the Cocos (Keeling) Islands, Australia
Authors: Lavers J. L. , Dicks L. , Dicks M. R. , Finger A.
Published: May 2019

For over 60 years, our oceans have been a reservoir for exponentially increasing amounts of plastic waste. Plastic has been documented at all levels of the marine food web, from the deepest oceanic trenches to the most far-flung beaches. Here, we present data on the presence of significant quantities of plastic on the remote Cocos (Keeling) Island group, located 2,100 km off the northwest coast of Australia. From our comprehensive surveys of debris on the beach surface, buried, and beach-back vegetation, we estimate there are 414 million anthropogenic debris items, weighing 238 tonnes, currently deposited on the Cocos (Keeling) Island group. Of the identifiable items, ~25% were classified as disposable plastics, including straws, bags, and toothbrushes. Debris buried up to 10 cm below the surface is estimated to account for 93% (~383 million items) of all debris present on Cocos, the majority of which (~60%) is comprised of micro-debris (2–5 mm). In the absence of meaningful change, debris will accumulate rapidly on the world’s beaches. Small, buried items pose considerable challenges for wildlife, and volunteers charged with the task of cleaning-up, thus preventing new items from entering the ocean remains key to addressing this issue.
Long-term field comparison of multiple low-cost particulate matter sensors in an outdoor urban environment
Authors: Bulot Florentin M. J. , Johnston Steven J. , Basford Philip J. , Easton Natasha H. C. , Apetroaie-Cristea Mihaela , Foster Gavin L. , Morris Andrew K. R. , Cox Simon J. , Loxham Matthew
Published: May 2019

Exposure to ambient particulate matter (PM) air pollution is a leading risk factor for morbidity and mortality, associated with up to 8.9 million deaths/year worldwide. Measurement of personal exposure to PM is hindered by poor spatial resolution of monitoring networks. Low-cost PM sensors may improve monitoring resolution in a cost-effective manner but there are doubts regarding data reliability. PM sensor boxes were constructed using four low-cost PM micro-sensor models. Three boxes were deployed at each of two schools in Southampton, UK, for around one year and sensor performance was analysed. Comparison of sensor readings with a nearby background station showed moderate to good correlation (0.61 < r < 0.88, p < 0.0001), but indicated that low-cost sensor performance varies with different PM sources and background concentrations, and to a lesser extent relative humidity and temperature. This may have implications for their potential use in different locations. Data also indicates that these sensors can track short-lived events of pollution, especially in conjunction with wind data. We conclude that, with appropriate consideration of potential confounding factors, low-cost PM sensors may be suitable for PM monitoring where reference-standard equipment is not available or feasible, and that they may be useful in studying spatially localised airborne PM concentrations.
Author Correction: Unsupervised Scalable Statistical Method for Identifying Influential Users in Online Social Networks
Authors: Azcorra A. , Chiroque L. F. , Cuevas R. , Anta A. Fernández , Laniado H. , Lillo R. E. , Romo J. , Sguera C.
Published: May 2019

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
Improving the Micropore Capacity of Activated Carbon by Preparation under a High Magnetic Field of 10 T
Authors: Hamasaki Atom , Furuse Ayumi , Sekinuma Yuya , Fujio Kazuki , Iide Masashi , Ozeki Sumio
Published: May 2019

The influence of an applied magnetic field on the formation of carbon materials from coal tar pitch is investigated. Under an applied magnetic field, crystallites in a mesophase resembling liquid crystals are magnetically oriented during the carbonization process. Compared with that under a nonmagnetic field, carbonized coal tar pitch under a strong magnetic field of 10 T, generated by a superconducting magnet, has a highly oriented structure of carbon crystallites. The orientation of samples prepared under 2 T, which can easily be supplied by an electromagnet, was insufficient. Activation by potassium hydroxide is effective for affording a precursor for activated carbon. The activated carbon obtained under a strong magnetic field has a unique adsorption ability, which arises from its increase in relative surface area and total pore volume compared with those of an activated carbon sample prepared from a precursor produced under zero magnetic field. The precursor carbonized under a magnetic field of 10 T contains a larger number of crystallites than that carbonized under a 0-T magnetic field, which leads to high-performance activated carbon.
Pharmaceutically modified subtilisins withstand acidic conditions and effectively degrade gluten in vivo
Authors: Darwish Ghassan , Helmerhorst Eva J. , Schuppan Detlef , Oppenheim Frank G. , Wei Guoxian
Published: May 2019

Detoxification of gluten immunogenic epitopes is a promising strategy for the treatment of celiac disease. Our previous studies have shown that these epitopes can be degraded in vitro by subtilisin enzymes derived from Rothia mucilaginosa, a natural microbial colonizer of the oral cavity. The challenge is that the enzyme is not optimally active under acidic conditions as encountered in the stomach. We therefore aimed to protect and maintain subtilisin-A enzyme activity by exploring two pharmaceutical modification techniques: PEGylation and Polylactic glycolic acid (PLGA) microencapsulation. PEGylation of subtilisin-A (Sub-A) was performed by attaching methoxypolyethylene glycol (mPEG, 5 kDa). The PEGylation protected subtilisin-A from autolysis at neutral pH. The PEGylated Sub-A (Sub-A-mPEG) was further encapsulated by PLGA. The microencapsulated Sub-A-mPEG-PLGA showed significantly increased protection against acid exposure in vitro. In vivo, gluten immunogenic epitopes were decreased by 60% in the stomach of mice fed with chow containing Sub-A-mPEG-PLGA (0.2 mg Sub-A/g chow) (n = 9) compared to 31.9% in mice fed with chow containing unmodified Sub-A (n = 9). These results show that the developed pharmaceutical modification can protect Sub-A from auto-digestion as well as from acid inactivation, thus rendering the enzyme more effective for applications in vivo.
Imaging local brain activity of multiple freely moving mice sharing the same environment
Authors: Inagaki Shigenori , Agetsuma Masakazu , Ohara Shinya , Iijima Toshio , Yokota Hideo , Wazawa Tetsuichi , Arai Yoshiyuki , Nagai Takeharu
Published: May 2019

Electrophysiological field potential dynamics have been widely used to investigate brain functions and related psychiatric disorders. Considering recent demand for its applicability to freely moving subjects, especially for animals in a group and socially interacting with each other, here we propose a new method based on a bioluminescent voltage indicator LOTUS-V. Using our fiber-free recording method based on the LOTUS-V, we succeeded in capturing dynamic change of brain activity in freely moving mice. Because LOTUS-V is the ratiometric indicator, motion and head-angle artifacts were not significantly detected. Taking advantage of our method as a fiber-free system, we further succeeded in simultaneously recording from multiple independently-locomotive mice that were freely interacting with one another. Importantly, this enabled us to find that the primary visual cortex, a center of visual processing, was activated during the interaction of mice. This methodology may further facilitate a wide range of studies in neurobiology and psychiatry.
A lasered mouse model of retinal degeneration displays progressive outer retinal pathology providing insights into early geographic atrophy
Authors: Ibbett Paul , Goverdhan Srinivas V. , Pipi Elena , Chouhan Joe K. , Keeling Eloise , Angus Elizabeth M. , Scott Jenny A. , Gatherer Maureen , Page Anton , Teeling Jessica L. , Lotery Andrew J. , Arjuna Ratnayaka J.
Published: May 2019

Early stages of geographic atrophy (GA) age-related macular degeneration is characterised by the demise of photoreceptors, which precedes the loss of underlying retinal pigment epithelial (RPE) cells. Sight-loss due to GA has no effective treatment; reflecting both the complexity of the disease and the lack of suitable animal models for testing potential therapies. We report the development and characterisation of a laser-induced mouse model with early GA-like pathology. Retinas were lasered at adjacent sites using a 810 nm laser (1.9 J/spot), resulting in the development of confluent, hypopigmented central lesions with well-defined borders. Optical Coherence Tomography over 2-months showed progressive obliteration of photoreceptors with hyper-reflective outer plexiform and RPE/Bruch’s membrane (BrM) layers within lesions, but an unaffected inner retina. Light/electron microscopy after 3-months revealed lesions without photoreceptors, leaving the outer plexiform layer apposed to the RPE. We observed outer segment debris, hypo/hyperpigmented RPE, abnormal apical-basal RPE surfaces and BrM thickening. Lesions had wedge-shaped margins, extended zones of damage, activated Müller cells, microglial recruitment and functional retinal deficits. mRNA studies showed complement and inflammasome activation, microglial/macrophage phagocytosis and oxidative stress providing mechanistic insights into GA. We propose this mouse model as an attractive tool for early GA studies and drug-discovery.
Structural and dynamic studies reveal that the Ala-rich region of ataxin-7 initiates α-helix formation of the polyQ tract but suppresses its aggregation
Authors: Hong Jun-Ye , Wang Dong-Dong , Xue Wei , Yue Hong-Wei , Yang Hui , Jiang Lei-Lei , Wang Wen-Ning , Hu Hong-Yu
Published: May 2019

Ataxin-7 (Atx7) is a disease-related protein associated with the pathogenesis of spinocerebellar ataxia 7, while its polyglutamine (polyQ) tract in N-terminus is the causative source of aggregation and proteinopathy. We investigated the structure, dynamics and aggregation properties of the N-terminal 62-residue fragment of Atx7 (Atx7-N) by biochemical and biophysical approaches. The results showed that the normal Atx7-N with a tract of 10 glutamines (10Q) overall adopts a flexible and disordered structure, but it may contain a short or small population of helical structure in solution. PolyQ expansion increases the α-helical propensity of the polyQ tract and consequently enhances its transformation into β-sheet structures during amyloid aggregation. An alanine-rich region (ARR) just ahead of the polyQ tract forms a local and relatively stable α-helix. The ARR α-helix can initiate and stabilize helical formation of the following polyQ tract, but it may suppress aggregation of the polyQ-expanded Atx7-N both in vitro and in cell. Thus, the preceding ARR segment in Atx7-N may influence the dynamic structure and aggregation property of the polyQ tract and even determine the threshold of the pathogenic polyQ lengths. This study may gain structural and dynamic insights into amyloid aggregation of Atx7 and help us further understand the Atx7 proteinopathy based on polyQ expansion.