Ökologie, Virulenz und Genomanalyse von Legionella pneumophila Isolaten aus der West Bank, Palästina

Legionella pneumophila is an environmental bacterium and a human pathogen causing life-threating outbreaks of an atypical pneumonia called Legionnaires’ disease. This study aimed to understand the diversity of L. pneumophila isolates, their clonal populations and the environmental driver of their abundance and prevalence in the West Bank. For this, a multi-annual seasonal sampling of nine drinking water sites in the West Bank were performed with a detailed recording of physico-chemical parameters. A total of 180 L. pneumophila isolates were obtained and analysed by high resolution genotyping (Multi-Locus Variable Number of Tandem Repeats (MLVA-8(12)). Also, physiological and virulence traits were studied. Genotyping and the studied traits led to the selection of representative strains submitted to high through-put genome sequencing (Illumina HiSeq and Pacific Biosciences platforms). Analysis of genotype prevalence in correspondence to environmental factors was used to elucidate genotype consortia and their environmental niches. The 180 isolates represented twenty-six individual MLVA-8(12) genotypes (Gt). The most frequently genotype was Gt4(17) (41.1%). All MLVA genotypes were clustered into four MLVA clonal complexes. Analysis of the prevalence of genotype indicated genotype consortia that seemed to be triggered by a set of environmental drivers. The concentration of several ions (Mg, Ca, Cl, SO4 and TDS) and turbidity seemed to determine niches for three different sets of genotypes and may explain their regional variability. Also, the abundance of L. pneumophila was influenced by these environmental drivers with Mg having a negative effect. The virulence of a representative subset of sixty environmental strains was assessed by five different in-vitro assays. Virulence traits were shown to be genotype dependent. A carefully selected subset of thirty-eight L. pneumophila isolates were genome sequenced and compared to already published reference genomes. Genome sequences were aligned with the sequence of the respective reference genome and analysed with respect to core-single nucleotide polymorphisms (core-SNPs), genomic islands and genes related to virulence traits. Overall, this study provided important insights into detailed population structure, the ecology and pathogenicity of this pathogen in the West Bank.Legionella pneumophila ist ein Umweltbakterium in Süsswassersystemen und humanpathogen; es verursacht lebensbedrohliche Ausbrüche der Legionärskrankheit, einer atypischen Pneumonie. Das Ziel der Doktorarbeit ist es, in der West Bank die Diversität von L. pneumophila-Isolaten, ihre clonale Populationsstruktur und die wesentlichen Umweltfaktoren, die Abundanz und Prävalenz steuern, zu verstehen. Hierzu wurde ein mehrjähriges saisonales Probenahmeprogramm für 9 Trinkwasserprobe-nahmestellen repräsentatv für die West Bank durchgeführt, bei dem physico-chemische und mikrobiologische Parameter mitaufgezeichnet wurden. 180 Isolate wurden hierbei gewonnen, hochauflösend genotypisiert (Multi-Locus Variable Number of Tandem Repeats (MLVA-8(12)), und hinsichtlich relevanter physiologischer Eigenschaften und Virulenzfaktoren analysiert. Die umfassende Charakterisierung der Isolate bildete die Grundlage zur Auswahl repräsentativer Stämme für die Genomsequenzierung mittels Illumina HiSeq und der Pac-Biosciences Platform. Die statistische Analyse von regionaler Genotypprävalenz und Umweltfaktoren wurde dazu genutzt um Genotypkonsortien und ihre Umweltnischen zu charakterisieren. Die 180 Isolate aus der Westbank zeigten eine hohe Genotypdiversität von 26 MLVA-8(12)-Genotypen, zugehörig zu vier MLVA clonalen Komplexen. Analysen der Prävalenz von Genotypen im Hinblick auf Umweltfaktoren zeigte, daß Konsortien von Genotypen durch Umweltfaktoren getriggert wurden. Unterschiedliche Konzentrationen von Ionen im Trinkwasser (Mg, Ca, Cl, SO4, TDS) and Trübung schienen Nischen für drei unterschiedliche Konsortien von Genotypen zu bestimmen, und könnten die räumliche Variabilität der Genotypen in der West Bank erklären und die Abundanz von L. pneumophila zu beeinflussen. Dabei schien Mg eine relevante Rolle zu spielen. Die Virulenz einer repräsentativen Untergruppe von 60 Isolaten wurde mit 5 in-vitro Ansätzen getestet. Die Virulenzstärke variierte in Abhängigkeit vom Genotyp mit relativ hoher Virulenz der häufigen Genotypen Gt4(17) und Gt6(18). Eine repräsentative Auswahl von 38 L. pneumophila Isolaten wurden genomsequenziert und mit Referenzgenomen und generierten eigenen Referenzgenomen verglichen, und hinsichtlich core-SNPs, genomischen Inseln und Virulenz-assoziierten Genen analysiert. Insgesamt gesehen, liefert die vorliegende Studie wichtige Einblicke zum Verständnis von Populationsstruktur, Ökologie und Pathogenität dieses pathogenen Bakteriums in der West Bank

Synthesis and Characterization of Zno Nanoparticles Using Hydrothermal and Sol-Gel Techniques for Dye-Sensitized Solar Cells

في هذا البحث تم تخليق جسيمات نانوية نقية من أكسيد الزنك باستخدام طريقتي الهيدروثيرمال وطريقة الصول جل. من فحوصات حيود الاشعة السينية تبين أن متوسط حجم الحبيبة تتراوح بين من 25 الي 28 نانومتر وتاخذ شكلا كرويا. فحوصات طيف الامتصاص بينت أن العينات جميعها لها اعلي امتصاص في منطقة الاشعة الفوق بنفسجية. وتم حساب فجوة الطاقة للعينات فوجد انها تساوي 3.13 eV و3.16 eV للعينة التي حضرت بطريقة الهيدروثيرمال والصول جل على الترتيب. تم تحضير عينات لخلايا شمسية صبغية وتم استخدام 3 انواع من الاصباغ الكيمياءية كمتحسسات ضوئية. فحوصات الاشعة الفوق بنفسجية بينت ان صبغة الايوزين الاصفر   Eosin Yتعطي اعلي امتصاص مقارنة بالاصباغ المستخدمة الاخري. تم رسم منحني الخواص لجميع العينات للخلايا الشمسية المحضرة وتم حساب جميع البارامترات اللازمة لتقييم اداء الخلية. العينة المصبوغة بصبغةEosin Y اعطت اعلي كفاءة Jsc = 4.25 (mA/cm2)، Voc = 0.51 V and η=1.08 %ZnO nanoparticles (ZnO NPs) were synthesized using hydrothermal and sol-gel techniques using zinc acetate dihydrate (Zn (CH3COO)2.2H2O) as a row material and methanol as a solvent. The structural properties of ZnO NPs were studied using EDX, XRD, TEM, and the optical properties were characterized using UV-VIS and PL spectroscopies. The synthesized ZnO NPs showed high purity and revealed a wurtzite (hexagonal) crystal structure with particle size (D) ranged from 25 nm to 28 nm. The UV-VIS absorption spectra of ZnO NPs samples and sensitizing dyes were performed. The obtained ZnO NPs exhibited the direct optical bandgap 3.15 eV. Dye-sensitized solar cells (DSSCs) were fabricated using synthesized ZnO NPs as a semiconducting layer, which was dyed with different low cost dyes such as Eosin B (EB), Eosin Y (EY) and Rhodamine B (RB) that was used to sensitize the photoanode (ZnO NPs). The experimental results showed a significant efficiency for the fabricated DSSCs of synthesized ZnO NPs via sol gel technique comparing to hydrothermal technique. The EY dye exhibited the best performance among others, where a conversion efficiency showed a noteworthy improvement from 0.12 to 1.08 %

Synthesis and characterization of ZnO nanoparticles using sol gel technique for dye sensitized solar cells applications

ZnO nanoparticles were synthesized using sol gel technique at differentcalcination temperature. The effect of calcination temperature on the structure and opticalproperties of ZnO NPs were studied in detail by using different techniques, X-raydiffraction, high-resolution transmission electron microscope, UV-VIS spectroscopy andphotoluminescence spectroscopy.X-ray diffractionanalysis revealed that the ZnO NPs werecrystalized in a wurtzite structure and the estimated average particle size increased from24.7 to40.4 nm with increasingcalcinationtemperature. In addition, the d spacingincreased from 0.28196 nm to 0.28213 nm.High-resolution transmission electronmicroscopy analysisimage showed spherical ZnONPs were formed. UV-VIS absorptionmeasurement was employed to evaluate the absorption edge and the optical band gapusingTauc plot. Energy gaprevealed a red shift from 3.15 to 2.96 eV when thecalcinationtemperaturewas increased. Dye sensitized solar cells were fabricated using synthesizedZnO NPs as a semiconducting layer that were dyed withdifferentXanthene(CH2[C6H4]2O)dyesseparately;(Eosin B, Eosin Y and Rhodamine B) which arelow costdyes. Thin layer of ZnO were deposited on transparentfluorine doped tin oxideconductiveglass using doctor blade method. Eosin Y exhibited the bestphotosensitizing. Theconversion efficiency showed a significant improvement from 0.1% to 1.08%.This research activity carried out between Gaza-Palestine and Cairo-Egypt, which was financially supported by Qatar Charity IBHATH Project grant funded by the Gulf Cooperation Council for the Reconstruction of Gaza through the Islamic Development Bank.ZnO nanoparticles were synthesized using sol gel technique at differentcalcination temperature. The effect of calcination temperature on the structure and opticalproperties of ZnO NPs were studied in detail by using different techniques, X-raydiffraction, high-resolution transmission electron microscope, UV-VIS spectroscopy andphotoluminescence spectroscopy.X-ray diffractionanalysis revealed that the ZnO NPs werecrystalized in a wurtzite structure and the estimated average particle size increased from24.7 to40.4 nm with increasingcalcinationtemperature. In addition, the d spacingincreased from 0.28196 nm to 0.28213 nm.High-resolution transmission electronmicroscopy analysisimage showed spherical ZnONPs were formed. UV-VIS absorptionmeasurement was employed to evaluate the absorption edge and the optical band gapusingTauc plot. Energy gaprevealed a red shift from 3.15 to 2.96 eV when thecalcinationtemperaturewas increased. Dye sensitized solar cells were fabricated using synthesizedZnO NPs as a semiconducting layer that were dyed withdifferentXanthene(CH2[C6H4]2O)dyesseparately;(Eosin B, Eosin Y and Rhodamine B) which arelow costdyes. Thin layer of ZnO were deposited on transparentfluorine doped tin oxideconductiveglass using doctor blade method. Eosin Y exhibited the bestphotosensitizing. Theconversion efficiency showed a significant improvement from 0.1% to 1.08%

Analytic Kramer kernels, Lagrange-type interpolation series and de Branges spaces

The classical Kramer sampling theorem provides a method for obtaining orthogonal sampling formulas. In particular, when the involved kernel is analytic in the sampling parameter it can be stated in an abstract setting of reproducing kernel Hilbert spaces of entire functions which includes as a particular case the classical Shannon sampling theory. This abstract setting allows us to obtain a sort of converse result and to characterize when the sampling formula associated with an analytic Kramer kernel can be expressed as a Lagrange-type interpolation series. On the other hand, the de Branges spaces of entire functions satisfy orthogonal sampling formulas which can be written as Lagrange-type interpolation series. In this work some links between all these ideas are established

Compromised BRCA1-PALB2 interaction is associated with breast cancer risk.

The major breast cancer suppressor proteins BRCA1 and BRCA2 play essential roles in homologous recombination (HR)-mediated DNA repair, which is thought to be critical for tumor suppression. The two BRCA proteins are linked by a third tumor suppressor, PALB2, in the HR pathway. While truncating mutations in these genes are generally pathogenic, interpretation of missense variants remains a challenge. To date, patient-derived missense variants that disrupt PALB2 binding have been identified in BRCA1 and BRCA2; however, there has not been sufficient evidence to prove their pathogenicity in humans, and no variants in PALB2 that disrupt either its BRCA1 or BRCA2 binding have been reported. Here we report on the identification of a novel PALB2 variant, c.104T>C (p.L35P), that segregates in a family with a strong history of breast cancer. Functional analyses showed that L35P abrogates the PALB2-BRCA1 interaction and completely disables its abilities to promote HR and confer resistance to platinum salts and PARP inhibitors. Whole-exome sequencing of a breast cancer from a c.104T>C carrier revealed a second, somatic, truncating mutation affecting PALB2, and the tumor displays hallmark genomic features of tumors with BRCA mutations and HR defects, cementing the pathogenicity of L35P. Parallel analyses of other germline variants in the PALB2 N-terminal BRCA1-binding domain identified multiple variants that affect HR function to varying degrees, suggesting their possible contribution to cancer development. Our findings establish L35P as the first pathogenic missense mutation in PALB2 and directly demonstrate the requirement of the PALB2-BRCA1 interaction for breast cancer suppression

Sanguinarine Induces Apoptosis in Papillary Thyroid Cancer Cells via Generation of Reactive Oxygen Species.

Sanguinarine (SNG), a natural compound with an array of pharmacological activities, has promising therapeutic potential against a number of pathological conditions, including malignancies. In the present study, we have investigated the antiproliferative potential of SNG against two well-characterized papillary thyroid cancer (PTC) cell lines, BCPAP and TPC-1. SNG significantly inhibited cell proliferation of PTC cells in a dose and time-dependent manner. Western blot analysis revealed that SNG markedly attenuated deregulated expression of p-STAT3, without affecting total STAT3, and inhibited growth of PTC via activation of apoptotic and autophagy signaling cascade, as SNG treatment of PTC cells led to the activation of caspase-3 and caspase-8; cleavage of PARP and activation of autophagy markers. Further, SNG-mediated anticancer effects in PTC cells involved the generation of reactive oxygen species (ROS) as N-acetyl cysteine (NAC), an inhibitor of ROS, prevented SNG-mediated antiproliferative, apoptosis and autophagy inducing action. Interestingly, SNG also sensitized PTC cells to chemotherapeutic drug cisplatin, which was inhibited by NAC. Finally, SNG suppressed the growth of PTC thyrospheres and downregulated stemness markers ALDH2 and SOX2. Altogether, the findings of the current study suggest that SNG has anticancer potential against PTC cells as well its derived cancer stem-like cells, most likely via inactivation of STAT3 and its associated signaling molecules