Early growth performances of various seed sources of black (Prunus serotina Erhr.) and wild cherry (Prunus avium L.) seedlings on low and high elevation sites in the western Black Sea Region of Turkey

The growth performances of one-year old seedlings of various black cherry (BC) and wild cherry (WC) seed sources (SSs) that were planted on low elevation sites (LES) and high elevation sites (HES) in the western Black Sea Region (BSR) of Turkey were assessed one and five years after planting (YAP). Significance between and within-species variations were found for seedling growth. On species basis, WC was superior to BC for seedling groundline diameter and height growth for the low elevation sites(LES) of one and five years after planting (YAP), whereas no substantial survival and growth differences were found between the species for the high elevation sites (HES) of five YAP. Generally, seedlings averaged a greater survival on the LES, when compared with those on the HES. Local WC SSs (Tefen, Yayla and Dirgine) demonstrated an enhanced seedling survival and growth on LES than the other SSs. Unlike the LES results, a collection of BC (Michigan 1 and Ukraine) and WC SSs (Dirgine, Germany, and Tefen) displayed the best seedling growth over five years. The HES seedlings frequently experienced diebacks and forking due to heavy snow fall and wildlife browsing. Selection of the local WC SSs was vital for the LES. However, BC SSs may present a potential for planting on the HES with harsher environmental conditions.Keywords: Black cherry, provenance test, seedling growth and survival, wild cherry

Telomerase and pluripotency factors jointly regulate stemness in pancreatic cancer stem cells

To assess the role of telomerase activity and telomere length in pancreatic CSCs we used different CSC enrichment methods (CD133, ALDH, sphere formation) in primary patient-derived pancreatic cancer cells. We show that CSCs have higher telomerase activity and longer telomeres than bulk tumor cells. Inhibition of telomerase activity, using genetic knockdown or pharmacological inhibitor (BIBR1532), resulted in CSC marker depletion, abrogation of sphere formation in vitro and reduced tumorigenicity in vivo. Furthermore, we identify a positive feedback loop between stemness factors (NANOG, OCT3/4, SOX2, KLF4) and telomerase, which is essential for the self-renewal of CSCs. Disruption of the balance between telomerase activity and stemness factors eliminates CSCs via induction of DNA damage and apoptosis in primary patient-derived pancreatic cancer samples, opening future perspectives to avoid CSC-driven tumor relapse. In the present study, we demonstrate that telomerase regulation is critical for the “stemness” maintenance in pancreatic CSCs and examine the effects of telomerase inhibition as a potential treatment option of pancreatic cancer. This may significantly promote our understanding of PDAC tumor biology and may result in improved treatment for pancreatic cancer patientsThis research was funded by a Max Eder Fellowship of the German Cancer Aid (111746), a German Cancer Aid Priority Program ‘Translational Oncology’ 70112505, by a Collaborative Research Centre grant (316249678—SFB 1279) of the German Research Foundation, and by a Hector Foundation Cancer Research grant (M65.1) to P.C.H., B.S.J. is supported by a Rámon y Cajal Merit Award (RYC- 2012-12104) from the Ministerio de Economía y Competitividad, Spain and a Coordinated grant (GC16173694BARB) from the Fundación Asociación Española Contra el Cáncer (AECC). K.W. is supported by a Baustein 3.2 by Ulm University

Functionalized Poly(3-hexylthiophene)s via Lithium–Bromine Exchange

Poly(3-hexylthiophene) (P3HT) is one of the most extensively investigated conjugated polymers and has been employed as the active material in many devices including field-effect transistors, organic photovoltaics and sensors. As a result, methods to further tune the properties of P3HT are desirable for specific applications. Herein, we report a facile postpolymerization modification strategy to functionalize the 4-position of commercially available P3HT in two simple steps–bromination of the 4-position of P3HT (Br–P3HT) followed by lithium−bromine exchange and quenching with an electrophile. We achieved near quantitative lithium–bromine exchange with Br–P3HT, which requires over 100 thienyl lithiates to be present on a single polymer chain. The lithiated-P3HT is readily combined with functional electrophiles, resulting in P3HT derivatives with ketones, secondary alcohols, trimethylsilyl (TMS) group, fluorine, or an azide at the 4-position. We demonstrated that the azide-modified P3HT could undergo Cu-catalyzed or Cu-free click chemistry, significantly expanding the complexity of the structures that can be appended to P3HT using this method.National Science Foundation (U.S.) (ECCS-0939514

Effectiveness and safety of opicapone in Parkinson's disease patients with motor fluctuations: The OPTIPARK open-label study

BACKGROUND: The efficacy and safety of opicapone, a once-daily catechol-O-methyltransferase inhibitor, have been established in two large randomized, placebo-controlled, multinational pivotal trials. Still, clinical evidence from routine practice is needed to complement the data from the pivotal trials. METHODS: OPTIPARK (NCT02847442) was a prospective, open-label, single-arm trial conducted in Germany and the UK under clinical practice conditions. Patients with Parkinson’s disease and motor fluctuations were treated with opicapone 50 mg for 3 (Germany) or 6 (UK) months in addition to their current levodopa and other antiparkinsonian treatments. The primary endpoint was the Clinician’s Global Impression of Change (CGI-C) after 3 months. Secondary assessments included Patient Global Impressions of Change (PGI-C), the Unified Parkinson’s Disease Rating Scale (UPDRS), Parkinson’s Disease Questionnaire (PDQ-8), and the Non-Motor Symptoms Scale (NMSS). Safety assessments included evaluation of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs). RESULTS: Of the 506 patients enrolled, 495 (97.8%) took at least one dose of opicapone. Of these, 393 (79.4%) patients completed 3 months of treatment. Overall, 71.3 and 76.9% of patients experienced any improvement on CGI-C and PGI-C after 3 months, respectively (full analysis set). At 6 months, for UK subgroup only (n = 95), 85.3% of patients were judged by investigators as improved since commencing treatment. UPDRS scores at 3 months showed statistically significant improvements in activities of daily living during OFF (mean ± SD change from baseline: − 3.0 ± 4.6, p < 0.0001) and motor scores during ON (− 4.6 ± 8.1, p < 0.0001). The mean ± SD improvements of − 3.4 ± 12.8 points for PDQ-8 and -6.8 ± 19.7 points for NMSS were statistically significant versus baseline (both p < 0.0001). Most of TEAEs (94.8% of events) were of mild or moderate intensity. TEAEs considered to be at least possibly related to opicapone were reported for 45.1% of patients, with dyskinesia (11.5%) and dry mouth (6.5%) being the most frequently reported. Serious TEAEs considered at least possibly related to opicapone were reported for 1.4% of patients. CONCLUSIONS: Opicapone 50 mg was effective and generally well-tolerated in PD patients with motor fluctuations treated in clinical practice. TRIAL REGISTRATION: Registered in July 2016 at clinicaltrials.gov (NCT02847442)

Recent advances in Pichia pastoris as host for heterologous expression system for lipases : a review

The production of heterologous lipases is one of the most promising strategies to increase the productivity of the bioprocesses and to reduce costs, with the final objective that more industrial lipase applications could be implemented. In this chapter, an overview of the new success in synthetic biology, with traditional molecular genetic techniques and bioprocess engineering in the last 5 years in the cell factory Pichia pastoris, the most promising host system for heterologous lipase production, is presented. The goals get on heterologous Candida antarctica, Rhizopus oryzae, and Candida rugosa lipases, three of the most common lipases used in biocatalysis, are showed. Finally, new cell factories producing heterologous lipases are presented

Impaired CK1 Delta Activity Attenuates SV40-Induced Cellular Transformation In Vitro and Mouse Mammary Carcinogenesis In Vivo

Simian virus 40 (SV40) is a powerful tool to study cellular transformation in vitro, as well as tumor development and progression in vivo. Various cellular kinases, among them members of the CK1 family, play an important role in modulating the transforming activity of SV40, including the transforming activity of T-Ag, the major transforming protein of SV40, itself. Here we characterized the effects of mutant CK1δ variants with impaired kinase activity on SV40-induced cell transformation in vitro, and on SV40-induced mammary carcinogenesis in vivo in a transgenic/bi-transgenic mouse model. CK1δ mutants exhibited a reduced kinase activity compared to wtCK1δ in in vitro kinase assays. Molecular modeling studies suggested that mutation N172D, located within the substrate binding region, is mainly responsible for impaired mutCK1δ activity. When stably over-expressed in maximal transformed SV-52 cells, CK1δ mutants induced reversion to a minimal transformed phenotype by dominant-negative interference with endogenous wtCK1δ. To characterize the effects of CK1δ on SV40-induced mammary carcinogenesis, we generated transgenic mice expressing mutant CK1δ under the control of the whey acidic protein (WAP) gene promoter, and crossed them with SV40 transgenic WAP-T-antigen (WAP-T) mice. Both WAP-T mice as well as WAP-mutCK1δ/WAP-T bi-transgenic mice developed breast cancer. However, tumor incidence was lower and life span was significantly longer in WAP-mutCK1δ/WAP-T bi-transgenic animals. The reduced CK1δ activity did not affect early lesion formation during tumorigenesis, suggesting that impaired CK1δ activity reduces the probability for outgrowth of in situ carcinomas to invasive carcinomas. The different tumorigenic potential of SV40 in WAP-T and WAP-mutCK1δ/WAP-T tumors was also reflected by a significantly different expression of various genes known to be involved in tumor progression, specifically of those involved in wnt-signaling and DNA repair. Our data show that inactivating mutations in CK1δ impair SV40-induced cellular transformation in vitro and mouse mammary carcinogenesis in vivo

Nanooptics of molecular-shunted plasmonic nanojunctions.

Gold nanoparticles are separated above a planar gold film by 1.1 nm thick self-assembled molecular monolayers of different conductivities. Incremental replacement of the nonconductive molecules with a chemically equivalent conductive version differing by only one atom produces a strong 50 nm blue-shift of the coupled plasmon. With modeling this gives a conductance of 0.17G(0) per biphenyl-4,4'-dithiol molecule and a total conductance across the plasmonic junction of 30G(0). Our approach provides a reliable tool quantifying the number of molecules in each plasmonic hotspot, here <200.We acknowledge financial support from EPSRC grant EP/ G060649/1, EP/I012060/1, EP/L027151/1, EP/K028510/1, ERC grant LINASS 320503. F.B. acknowledges support from the Winton Programme for the Physics of Sustainability. C.T. and J.A. acknowledge financial support from Project FIS2013- 41184-P from MINECO, ETORTEK 2014-15 of the Basque Department of Industry and IT756-13 from the Basque consolidated groups.This paper was originally published in Nano Letters under a CC-BY licence (F Benz, C Tserkezis, LO Herrmann, B de Nijs, A Sanders, DO Sigle, L Pukenas, SD Evans, J Aizpurua, JJ Baumberg, Nano Letters 2015, 15, 669−674

Effects of peeling methods on the quality of cubiu fruits

Cubiu (Solanum sessiliflorum Dunal) is an Amazonian Basin native fruit. Its importance comes from its high contents of pectin. Currently, processing technologies are necessary for the substitution of the traditional system (small crops and small-scale processing) for a larger scale system and thus increase the use of biodiversity and promote the implementation of Local Productive Arrangements of agribusiness in the Amazon. This research aims to evaluate the methods of peeling cubiu. Ripe fruits were divided into lots (150 each) and subjected to the following treatments: immersion in 2.5% NaOH boiling solution for 5 minutes, exposure to water vapor, and immersion in water at 96 ºC for 5, 10, 15 and 20 minutes. The peel released during heat treatment and immediately removed under running tap water. In the control treatment, the fruits were manually peeled (unheated) with a stainless steel knife. The treatments were evaluated for completeness and ease of peeling, tissue integrity, texture, and peroxidase activity. The immersion in 2.5% NaOH boiling solution (5 minutes) stood out as the best treatment since it inhibited the enzymatic browning and intensified the natural yellow color of the cubiu fruit and easily and fully peeled the whole fruit more rapidly without damaging its tissues. This treatment was chosen as the most advantageous because it can promote simultaneous peeling and bleaching. Therefore, it is recommended for cubiu industrial processing