Evaluation des WWW - Suchdienstes GERHARD unter besonderer Beachtung der automatischen Indexierung

Die vorliegende Arbeit beinhaltet eine Beschreibung und Evaluation des WWW - Suchdienstes GERHARD (German Harvest Automated Retrieval and Directory). GERHARD ist ein Such- und Navigationssystem für das deutsche World Wide Web, welches ausschließlich wissenschaftlich relevante Dokumente sammelt, und diese auf der Basis computerlinguistischer und statistischer Methoden automatisch mit Hilfe eines bibliothekarischen Klassifikationssystems klassifiziert

Quantitative single-molecule imaging of TLR4 reveals ligand-specific receptor dimerization

In humans, invading pathogens are recognized by Toll-like receptors (TLRs). Upon recognition of lipopolysaccharide (LPS) derived from the cell wall of gram-negative bacteria, TLR4 dimerizes and can stimulate two different signaling pathways, the proinflammatory, MyD88-dependent pathway and the antiviral, MyD88-independent pathway. The balance between these two pathways is ligand-dependent, and ligand composition determines whether the invading pathogen activates or evades the host immune response. We investigated the dimerization behavior of TLR4 in intact cells in response to different LPS chemotypes through quantitative single-molecule localization microscopy (SMLM). Quantitative super-resolved data showed that TLR4 was monomeric in the absence of its coreceptors MD2 and CD14 in transfected HEK 293 cells. When TLR4 was present together with MD2 and CD14, but in the absence of LPS, 52% of the receptors were monomeric and 48% were dimeric. LPS from Escherichia coli or Salmonella minnesota caused the formation of dimeric TLR4 complexes, whereas the antagonistic LPS chemotype from Rhodobacter sphaeroides maintained TLR4 in monomeric form at the cell surface. Furthermore, we showed that LPS-dependent dimerization was required for the activation of NF-κB signaling. Together, these data demonstrate ligand-dependent dimerization of TLR4 in the cellular environment, which could pave the way for a molecular understanding of biased signaling downstream of the receptor

Predictors of human papillomavirus infection in women undergoing routine cervical cancer screening in Spain : the CLEOPATRE study

Human papillomavirus (HPV) is a sexually transmitted infection that may lead to development of precancerous and cancerous lesions of the cervix. The aim of the current study was to investigate socio-demographic, lifestyle, and medical factors for potential associations with cervical HPV infection in women undergoing cervical cancer screening in Spain. The CLEOPATRE Spain study enrolled 3 261 women aged 18-65 years attending cervical cancer screening across the 17 Autonomous Communities. Liquid-based cervical samples underwent cytological examination and HPV testing. HPV positivity was determined using the Hybrid Capture II assay, and HPV genotyping was conducted using the INNO-LiPA HPV Genotyping Extra assay. Multivariate logistic regression was used to identify putative risk factors for HPV infection. A lifetime number of two or more sexual partners, young age (18-25 years), a history of genital warts, and unmarried status were the strongest independent risk factors for HPV infection of any type. Living in an urban community, country of birth other than Spain, low level of education, and current smoking status were also independent risk factors for HPV infection. A weak inverse association between condom use and HPV infection was observed. Unlike monogamous women, women with two or more lifetime sexual partners showed a lower risk of infection if their current partner was circumcised (P for interaction, 0.005) and a higher risk of infection if they were current smokers (P for interaction, 0.01). This is the first large-scale, country-wide study exploring risk factors for cervical HPV infection in Spain. The data strongly indicate that variables related to sexual behavior are the main risk factors for HPV infection. In addition, in non-monogamous women, circumcision of the partner is associated with a reduced risk and smoking with an increased risk of HPV infection

Predictors of human papillomavirus infection in women undergoing routine cervical cancer screening in Spain: the CLEOPATRE study

Background: Human papillomavirus (HPV) is a sexually transmitted infection that may lead to development of precancerous and cancerous lesions of the cervix. The aim of the current study was to investigate sociodemographic, lifestyle, and medical factors for potential associations with cervical HPV infection in women undergoing cervical cancer screening in Spain. Methods: The CLEOPATRE Spain study enrolled 3 261 women aged 18–65 years attending cervical cancer screening across the 17 Autonomous Communities. Liquid-based cervical samples underwent cytological examination and HPV testing. HPV positivity was determined using the Hybrid Capture II assay, and HPV genotyping was conducted using the INNO-LiPA HPV Genotyping Extra assay. Multivariate logistic regression was used to identify putative risk factors for HPV infection. Results: A lifetime number of two or more sexual partners, young age (18–25 years), a history of genital warts, and unmarried status were the strongest independent risk factors for HPV infection of any type. Living in an urban community, country of birth other than Spain, low level of education, and current smoking status were also independent risk factors for HPV infection. A weak inverse association between condom use and HPV infection was observed. Unlike monogamous women, women with two or more lifetime sexual partners showed a lower risk of infection if their current partner was circumcised (P for interaction, 0.005) and a higher risk of infection if they were current smokers (P for interaction, 0.01). Conclusion: This is the first large-scale, country-wide study exploring risk factors for cervical HPV infection in Spain. The data strongly indicate that variables related to sexual behavior are the main risk factors for HPV infection. In addition, in non-monogamous women, circumcision of the partner is associated with a reduced risk and smoking with an increased risk of HPV infection

Analysis of Y chromosome STR haplotypes in the European part of Russia reveals high diversities but non-significant genetic distances between populations

A total of 17 Y-specific STR loci were studied in 12 districts of the European part of Russia aiming to ascertain the amount of substructure required for the construction of a representative regional database. All groups exhibited high haplotype diversities but low inter-population variance as measured by an analysis of molecular variance. However, when Western Russia is taken as a whole, the genetic distances to the neighbouring populations were significant. Whereas gradual change in the Y chromosome pool exists between Russia and the Slavic-speaking populations to the West, remarkable discontinuities were observed with neighbouring populations in the East, North and South

Comprehensive mutation analysis of 17 Y-chromosomal short tandem repeat polymorphisms included in the AmpFlSTR® Yfiler® PCR amplification kit

The Y-chromosomal short tandem repeat (Y-STR) polymorphisms included in the AmpFlSTR® Yfiler® polymerase chain reaction amplification kit have become widely used for forensic and evolutionary applications where a reliable knowledge on mutation properties is necessary for correct data interpretation. Therefore, we investigated the 17 Yfiler Y-STRs in 1,730–1,764 DNA-confirmed father–son pairs per locus and found 84 sequence-confirmed mutations among the 29,792 meiotic transfers covered. Of the 84 mutations, 83 (98.8%) were single-repeat changes and one (1.2%) was a double-repeat change (ratio, 1:0.01), as well as 43 (51.2%) were repeat gains and 41 (48.8%) repeat losses (ratio, 1:0.95). Medians from Bayesian estimation of locus-specific mutation rates ranged from 0.0003 for DYS448 to 0.0074 for DYS458, with a median rate across all 17 Y-STRs of 0.0025. The mean age (at the time of son’s birth) of fathers with mutations was with 34.40 (±11.63) years higher than that of fathers without ones at 30.32 (±10.22) years, a difference that is highly statistically significant (p < 0.001). A Poisson-based modeling revealed that the Y-STR mutation rate increased with increasing father’s age on a statistically significant level (α = 0.0294, 2.5% quantile = 0.0001). From combining our data with those previously published, considering all together 135,212 meiotic events and 331 mutations, we conclude for the Yfiler Y-STRs that (1) none had a mutation rate of >1%, 12 had mutation rates of >0.1% and four of <0.1%, (2) single-repeat changes were strongly favored over multiple-repeat ones for all loci but 1 and (3) considerable variation existed among loci in the ratio of repeat gains versus losses. Our finding of three Y-STR mutations in one father–son pair (and two pairs with two mutations each) has consequences for determining the threshold of allelic differences to conclude exclusion constellations in future applications of Y-STRs in paternity testing and pedigree analyses

Redox activities and ROS, NO and phenylpropanoids production by axenically cultured intact olive seedling roots after interaction with a mycorrhizal or a pathogenic fungus

Las raíces de las plántulas de olivo, en cultivo axénico, fueron colocadas alternativamente en contacto con Rhizophagus irregulares (micorrícicos) o con hongos Verticillim dahliae (patógenos). También se incluyeron tratamientos MeJA. Las raíces intactas (generación de anión superóxido, superóxido dismutasa y actividades de peroxidasa) se midieron en las actividades in vivo del apoplasto. Todos nuestros resultados mostraron que las actividades redox apoplásticas de raíces de las plántulas intactas en contacto con el hongo micorriza compatible fueron claramente atenuados en comparación con el hongo patógeno o tratado con MeJA, incluso en las primeras etapas usadas en el tratamiento. Los fenoles totales, flavonoides y glucósidos fenilpropanoides, también fueron cuantificados. Las raíces en contacto con el hongo micorriza no mejoraron la biosíntesis de compuestos fenólicos con respecto a los controles, mientras que los de contacto con el patógeno mejoraron de forma significativa la biosíntesis de todas las fracciones fenólicas medidas. Las especies reactivas del oxígeno y la acumulación de óxido nítrico en las raíces fueron examinadas por microscopía de fluorescencia. Todos ellas presentaron una acumulación mucho mayor en las raíces en contacto con el patógeno que con el hongo micorriza. En total, estos resultados indican que las raíces de las plántulas intactas de olivo, claramente diferenciadas entre micorrizas y hongos patógenos, atenuan las reacciones de defensa contra la primera para facilitar su creación, mientras que induce una reacción de defensa fuerte y sostenida contra el segundo. Ambas especies reactivas de oxígeno y nitrógeno parecían estar involucrados en estas respuestas desde los primeros momentos de contacto. Sin embargo, se necesitan más investigaciones para aclarar la diafonía propuesta entre ellos y sus respectivas funciones en estas respuestas ya que las imágenes de fluorescencia de las raíces revelaron que las especies reactivas del oxígeno se acumulan principalmente en el apoplasto (congruente con las actividades redox medidas en este compartimento), mientras el óxido nítrico se almacena principalmente en el citosol.Roots of intact olive seedlings, axenically cultured, were alternatively placed in contact with Rhizophagus irregularis (mycorrhizal) or Verticillim dahliae (pathogenic) fungi. MeJA treatments were also included. In vivo redox activities in the apoplast of the intact roots (anion superoxide generation, superoxide dismutase and peroxidase activities) were measured. All our results showed that apoplastic redox activities of intact seedling roots in contact with the compatible mycorrhizal fungus were clearly attenuated in comparison with the pathogenic fungus or treated with MeJA, even at the early stages of treatment used. Total phenolics, flavonoids and phenylpropanoid glycosides were also quantified. Roots in contact with the mycorrhizal fungus did not enhance the biosynthesis of phenolic compounds with respect to controls, while those in contact with the pathogenic one significantly enhanced the biosynthesis of all phenolic fractions measured. Reactive oxygen species and nitric oxid accumulation in roots were examined by fluorescence microscopy. All of them presented much higher accumulation in roots in contact with the pathogenic than with the mycorrhizal fungus. Altogether these results indicate that intact olive seedling roots clearly differentiated between mycorrhizal and pathogenic fungi, attenuating defense reactions against the first to facilitate its establishment, while inducing a strong and sustained defense reaction against the second. Both reactive oxygen and nitrogen species seemed to be involved in these responses from the first moments of contact. However, further investigations are required to clarify the proposed crosstalk between them and their respective roles in these responses since fluorescence images of roots revealed that reactive oxygen species were mainly accumulated in the apoplast (congruently with the measured redox activities in this compartment) while nitric oxid was mainly stored in the cytosol.-- Ministerio de Ciencia e Innovación. Proyecto CGL2009-12406 -- Junta de Extremadura. Proyecto PRI09A023peerReviewe

Detectives de alimentos: un trabajo en equipo para la investigación de toxiinfecciones alimentarias

Proyecto de Innovación Docente en el que los estudiantes realizan un trabajo cooperativo mediante el método del puzle para diseñar fichas descriptivas de patógenos de transmisión alimentaria y resolver un caso de toxiinfección alimentari

The German National Registry of Primary Immunodeficiencies (2012-2017)

Introduction: The German PID-NET registry was founded in 2009, serving as the first national registry of patients with primary immunodeficiencies (PID) in Germany. It is part of the European Society for Immunodeficiencies (ESID) registry. The primary purpose of the registry is to gather data on the epidemiology, diagnostic delay, diagnosis, and treatment of PIDs. Methods: Clinical and laboratory data was collected from 2,453 patients from 36 German PID centres in an online registry. Data was analysed with the software Stata® and Excel. Results: The minimum prevalence of PID in Germany is 2.72 per 100,000 inhabitants. Among patients aged 1–25, there was a clear predominance of males. The median age of living patients ranged between 7 and 40 years, depending on the respective PID. Predominantly antibody disorders were the most prevalent group with 57% of all 2,453 PID patients (including 728 CVID patients). A gene defect was identified in 36% of patients. Familial cases were observed in 21% of patients. The age of onset for presenting symptoms ranged from birth to late adulthood (range 0–88 years). Presenting symptoms comprised infections (74%) and immune dysregulation (22%). Ninety-three patients were diagnosed without prior clinical symptoms. Regarding the general and clinical diagnostic delay, no PID had undergone a slight decrease within the last decade. However, both, SCID and hyper IgE- syndrome showed a substantial improvement in shortening the time between onset of symptoms and genetic diagnosis. Regarding treatment, 49% of all patients received immunoglobulin G (IgG) substitution (70%—subcutaneous; 29%—intravenous; 1%—unknown). Three-hundred patients underwent at least one hematopoietic stem cell transplantation (HSCT). Five patients had gene therapy. Conclusion: The German PID-NET registry is a precious tool for physicians, researchers, the pharmaceutical industry, politicians, and ultimately the patients, for whom the outcomes will eventually lead to a more timely diagnosis and better treatment