Miracle-dz/UniFAR-FTUs huggingface dataset:
Immunomodulatory activity of extracellular heat shock proteins and their autoantibodies

HSP are groups of stress‐inducible proteins which contribute to quality control by assisting the correct folding of both nascent and denatured proteins, and promoting the degradation of unrecoverable denatured proteins. HSP also help to maintain cellular homeostasis and protect from cell death through a mechanism called thermotolerance. Cells subjected to mild stress induce HSP which then protect them against subsequent stress. However, in cells subjected to severe stress, HSP promote apoptosis. Besides these intracellular events, HSP also exist in extracellular fluids, and have been shown to contribute to immunomodulation. In innate immunity extracellular HSP, like various microbial substances, induce various proinflammatory cytokines. In acquired immunity they interact with antigenic polypeptides and assist in antigen presentation. The extracellular HSP are so‐called adjuvant. Release of HSP from cells is triggered by stress and trauma, and is thus regarded as an immunological “danger signal”. In addition, anti‐HSP autoantibodies are frequently found in patients with autoimmune diseases and inflammatory disorders, and these autoantibodies can modulate the “danger signal” triggered by extracellular HSP.
Nanomaterial‐Enabled Wearable Sensors for Healthcare

Highly sensitive wearable sensors that can be conformably attached to human skin or integrated with textiles to monitor the physiological parameters of human body or the surrounding environment have garnered tremendous interest. Owing to the large surface area and outstanding material properties, nanomaterials are promising building blocks for wearable sensors. Recent advances in the nanomaterial‐enabled wearable sensors including temperature, electrophysiological, strain, tactile, electrochemical, and environmental sensors are presented in this review. Integration of multiple sensors for multimodal sensing and integration with other components into wearable systems are summarized. Representative applications of nanomaterial‐enabled wearable sensors for healthcare, including continuous health monitoring, daily and sports activity tracking, and multifunctional electronic skin are highlighted. Finally, challenges, opportunities, and future perspectives in the field of nanomaterial‐enabled wearable sensors are discussed.
DNA-PK triggers histone ubiquitination and signaling in response to DNA double-strand breaks produced during the repair of transcription-blocking topoisomerase I lesions

Although defective repair of DNA double-strand breaks (DSBs) leads to neurodegenerative diseases, the processes underlying their production and signaling in non-replicating cells are largely unknown. Stabilized topoisomerase I cleavage complexes (Top1cc) by natural compounds or common DNA alterations are transcription-blocking lesions whose repair depends primarily on Top1 proteolysis and excision by tyrosyl–DNA phosphodiesterase-1 (TDP1). We previously reported that stabilized Top1cc produce transcription-dependent DSBs that activate ATM in neurons. Here, we use camptothecin (CPT)-treated serum-starved quiescent cells to induce transcription-blocking Top1cc and show that those DSBs are generated during Top1cc repair from Top1 peptide-linked DNA single-strand breaks generated after Top1 proteolysis and before excision by TDP1. Following DSB induction, ATM activates DNA-PK whose inhibition suppresses H2AX and H2A ubiquitination and the later assembly of activated ATM into nuclear foci. Inhibition of DNA-PK also reduces Top1 ubiquitination and proteolysis as well as resumption of RNA synthesis suggesting that DSB signaling further enhances Top1cc repair. Finally, we show that co-transcriptional DSBs kill quiescent cells. Together, these new findings reveal that DSB production and signaling by transcription-blocking Top1 lesions impact on non-replicating cell fate and provide insights on the molecular pathogenesis of neurodegenerative diseases such as SCAN1 and AT syndromes, which are caused by TDP1 and ATM deficiency, respectively.
Low endotoxic activity of lipopolysaccharides isolated from Bradyrhizobium, Mesorhizobium, and Azospirillum strains

The endotoxic activities of lipopolysaccharides (LPS) isolated from different strains of rhizobia and rhizobacteria (Bradyrhizobium, Mesorhizobium, and Azospirillum) were compared to those of Salmonella enterica sv. Typhimurium LPS. The biological activity of all the examined preparations, measured as Limulus lysate gelation, production of tumor necrosis factor (TNF), interleukin‐1β (IL‐1β), and interleukin‐6 (IL‐6), and nitrogen oxide (NO) induction in human myelomonocytic cells (line THP‐1), was considerably lower than that of the reference enterobacterial endotoxin. Among the rhizobial lipopolysaccharides, the activities of Mesorhizobium huakuii and Azospirillum lipoferum LPSs were higher than those of the LPS preparations from five strains of Bradyrhizobium. The weak endotoxic activity of the examined preparations was correlated with differences in lipid A structure compared to Salmonella.
Therapeutic target database update 2016: enriched resource for bench to clinical drug target and targeted pathway information

Extensive drug discovery efforts have yielded many approved and candidate drugs targeting various targets in different biological pathways. Several freely accessible databases provide the drug, target and drug-targeted pathway information for facilitating drug discovery efforts, but there is an insufficient coverage of the clinical trial drugs and the drug-targeted pathways. Here, we describe an update of the Therapeutic Target Database (TTD) previously featured in NAR. The updated contents include: (i) significantly increased coverage of the clinical trial targets and drugs (1.6 and 2.3 times of the previous release, respectively), (ii) cross-links of most TTD target and drug entries to the corresponding pathway entries of KEGG, MetaCyc/BioCyc, NetPath, PANTHER pathway, Pathway Interaction Database (PID), PathWhiz, Reactome and WikiPathways, (iii) the convenient access of the multiple targets and drugs cross-linked to each of these pathway entries and (iv) the recently emerged approved and investigative drugs. This update makes TTD a more useful resource to complement other databases for facilitating the drug discovery efforts. TTD is accessible at http://bidd.nus. edu.sg/group/ttd/ttd.asp.
AREsite2: an enhanced database for the comprehensive investigation of AU/GU/U-rich elements

AREsite2 represents an update for AREsite, an on-line resource for the investigation of AU-rich elements (ARE) in human and mouse mRNA 3′UTR sequences. The new updated and enhanced version allows detailed investigation of AU, GU and U-rich elements (ARE, GRE, URE) in the transcriptome of Homo sapiens, Mus musculus, Danio rerio, Caenorhabditis elegans and Drosophila melanogaster. It contains information on genomic location, genic context, RNA secondary structure context and conservation of annotated motifs. Improvements include annotation of motifs not only in 3′UTRs but in the whole gene body including introns, additional genomes, and locally stable secondary structures from genome wide scans. Furthermore, we include data from CLIP-Seq experiments in order to highlight motifs with validated protein interaction. Additionally, we provide a REST interface for experienced users to interact with the database in a semi-automated manner. The database is publicly available at: http://rna.tbi. univie.ac. at/AREsite
Conversion of mono‐polar to peritrichous flagellation in Vibrio alginolyticus

Precise regulation of the number and positioning of flagella are critical in order for the mono‐polar‐flagellated bacterium Vibrio alginolyticus to swim efficiently. It has been shown that, in V. alginolyticus cells, the putative GTPase FlhF determines the polar location and production of flagella, while the putative ATPase FlhG interacts with FlhF, preventing it from localizing at the pole, and thus negatively regulating the flagellar number. In fact, no ΔflhF cells have flagella, while a very small fraction of ΔflhFG cells possess peritrichous flagella. In this study, the mutants that suppress inhibition of the swarming ability of ΔflhFG cells were isolated. The mutation induced an increase in the flagellar number and, furthermore, most Vibrio cells appeared to have peritrichous flagella. The sequence of the flagella related genes was successfully determined, however, the location of the suppressor mutation could not been found. When the flhF gene was introduced into the suppressor mutant, multiple polar flagella were generated in addition to peritrichous flagella. On the other hand, introduction of the flhG gene resulted in the loss of most flagella. These results suggest that the role of FlhF is bypassed through a suppressor mutation which is not related to the flagellar genes.
Evolution of Infectious Disease

Course Description: Evolution underlies every aspect of biology, but many people have an impression that evolution is restricted to the study of fossils revealing how large organisms are related to one another. Evolution continues to occur, and we can study both microevolution and macroevolution of microbes within human lifetimes. We will survey how pathogenic microorganisms have evolved, with an emphasis on understanding how the same evolutionary principles that we infer from large eukaryotic species can be concretely observed in viruses, bacteria and eukaryotic parasites. This course will highlight the rapidity with which microbes respond to changing ecology, including human interventions, and the mechanisms of creating and maintaining population variation that underlies this adaptability. Through studying the evolution of specific pathogens in depth, the role of both natural selection and genetic drift will be illustrated. The practical applications of experimental evolution and evolutionary theory in designing vaccines, drugs and other interventions against infectious disease will also be covered. While some microbial biology and immunology will be taught as a necessary component of understanding microbial evolution, this will not be a course in pathogenic microbiology, and will focus on the evolution of viruses, bacteria and a few eukaryotic pathogens. In addition to the lectures, students are expected to learn some course concepts directly from the primary scientific literature and from a wide range of media that communicate science to the public: a bestselling book on emerging diseases, the New York Times, science bloggers, podcasts and YouTube clips produced by scientists. Students will demonstrate their own ability to contribute to the discussion of evolutionary principles and research by producing two blog posts, which will be available on the course sakai site, but not available to the general public/search engines. Course Goals: Through the course readings, lectures and assignments you will understand and apply basic principles and concepts in the biological sciences (evolution and microbiology). In course assignments, you will use current technologies to access information, to conduct research, and to communicate findings. Through blogging about the research, you will use an emerging mode of scientific communication to communicate complex ideas effectively, in standard written English, to a general audience. You will demonstrate that you can communicate effectively in modes appropriate to this area of inquiry (evolution) and that you can evaluate and critically assess sources and use the conventions of attribution and citation correctly.
Krebs in Deutschland 2005/2006 - Häufigkeiten und Trends

Die Broschüre »Krebs in Deutschland« wird alle zwei Jahre als gemeinsame Publikation der Gesellschaft der epidemiologischen Krebsregister e. V. (GEKID) und des Robert KochInstituts (RKI) herausgegeben. Die vorliegende 6. Auflage erscheint mit neuem Design erstmalig in der Reihe der Berichte der Gesundheitsberichterstattung (GBE) des Bundes. Sie enthält Angaben zu den in Deutschland im Zeitraum von 1980 bis zum Jahr 2004 insgesamt aufgetretenen Krebsneuerkrankungen und zu ausgewählten Einzellokalisationen, die jeweils kurz und übersichtlich dargestellt werden (Erkrankungsund Sterberaten, Risikofaktoren, Trendverläufe, Überlebensaussichten). Die aktuellen Schätzungen des RKI basieren auf den Daten vollzählig erfassender epidemiologischer Krebsregister in Deutschland. Für das Jahr 2004 weist diese Schätzung insgesamt 436.500 Krebsneuerkrankungen aus (Männer 230.500, Frauen 206.000). Damit sind im Vergleich zur vorangegangenen Schätzung, die mit dem Jahr 2002 abschloss, im Jahr 2004 etwa 12.000 Krebsneuerkrankungen mehr aufgetreten. Bei Frauen blieb die Gesamtzahl dieser Erkrankungen gegenüber 2002 unverändert. Die zusätzlichen Erkrankungsfälle im Jahr 2004 sind überwiegend auf Erkrankungen der Männer an Prostatakrebs zurückzuführen, der mit etwa 58.500 Erkrankungsfällen die häufigste Krebserkrankung bei Männer darstellt. Bei den Frauen steht, wie in den vorangegangenen Schätzungen auch, der Brustkrebs mit etwa 57.000 Neuerkrankungen an erster Stelle. Im Jahr 2004 verstarben insgesamt 208.800 Personen in Deutschland an Krebs, im Jahr 2002 waren es noch 209.900. Die Überlebensaussichten mit Prostatakrebs und Brustkrebs haben sich so weit verbessert, dass die Zahl der Krebssterbefälle daran mittlerweile abnimmt. Im Jahr 2004 verstarben 11.200 Männer an Prostatakrebs und 17.600 Frauen an Brustkrebs. Das sind jeweils 200 Sterbefälle weniger als noch zwei Jahre zuvor. Angaben zu Krebs erkrankungen bei Kindern werden vom Kinderkrebsregister Mainz in einem eigenen Abschnitt der Broschüre dargestellt.
Gold Nanocages for Biomedical Applications

Nanostructured materials provide a promising platform for early cancer detection and treatment. Here we highlight recent advances in the synthesis and use of Au nanocages for such biomedical applications. Gold nanocages represent a novel class of nanostructures, which can be prepared via a remarkably simple route based on the galvanic replacement reaction between Ag nanocubes and HAuCl4. The Au nanocages have a tunable surface plasmon resonance peak that extends into the near‐infrared, where the optical attenuation caused by blood and soft tissue is essentially negligible. They are also biocompatible and present a well‐established surface for easy functionalization. We have tailored the scattering and absorption cross‐sections of Au nanocages for use in optical coherence tomography and photothermal treatment, respectively. Our preliminary studies show greatly improved spectroscopic image contrast for tissue phantoms containing Au nanocages. Our most recent results also demonstrate the photothermal destruction of breast cancer cells in vitro by using immuno‐targeted Au nanocages as an effective photo‐thermal transducer. These experiments suggest that Au nanocages may be a new class of nanometer‐sized agents for cancer diagnosis and therapy.
Virological surveillance of human influenza in Indonesia, October 2008‐March 2010

Despite the high prevalence of highly pathogenic H5N1 influenza A viruses in Indonesia, epidemiology information on seasonal human influenza is lacking. The present authors, therefore, conducted virologic surveillance in Surabaya, East Java from October 2008 to March 2010. Influenza viruses, including pandemic (H1N1) 2009 viruses, were isolated from 71 of 635 individuals tested. Seasonal influenza peaked in the rainy season. Compared with seasonal influenza viruses, pandemic 2009 viruses were isolated from younger patients with milder symptoms. Given the high prevalence of H5N1 infections in humans, continued influenza surveillance is essential for pandemic preparedness.
Phosphorylation of Ku dictates DNA double-strand break (DSB) repair pathway choice in S phase

Multiple DNA double-strand break (DSB) repair pathways are active in S phase of the cell cycle; however, DSBs are primarily repaired by homologous recombination (HR) in this cell cycle phase. As the non-homologous end-joining (NHEJ) factor, Ku70/80 (Ku), is quickly recruited to DSBs in S phase, we hypothesized that an orchestrated mechanism modulates pathway choice between HR and NHEJ via displacement of the Ku heterodimer from DSBs to allow HR. Here, we provide evidence that phosphorylation at a cluster of sites in the junction of the pillar and bridge regions of Ku70 mediates the dissociation of Ku from DSBs. Mimicking phosphorylation at these sites reduces Ku's affinity for DSB ends, suggesting that phosphorylation of Ku70 induces a conformational change responsible for the dissociation of the Ku heterodimer from DNA ends. Ablating phosphorylation of Ku70 leads to the sustained retention of Ku at DSBs, resulting in a significant decrease in DNA end resection and HR, specifically in S phase. This decrease in HR is specific as these phosphorylation sites are not required for NHEJ. Our results demonstrate that the phosphorylation-mediated dissociation of Ku70/80 from DSBs frees DNA ends, allowing the initiation of HR in S phase and providing a mechanism of DSB repair pathway choice in mammalian cells.
MRPrimer: a MapReduce-based method for the thorough design of valid and ranked primers for PCR

Primer design is a fundamental technique that is widely used for polymerase chain reaction (PCR). Although many methods have been proposed for primer design, they require a great deal of manual effort to generate feasible and valid primers, including homology tests on off-target sequences using BLAST-like tools. That approach is inconvenient for many target sequences of quantitative PCR (qPCR) due to considering the same stringent and allele-invariant constraints. To address this issue, we propose an entirely new method called MRPrimer that can design all feasible and valid primer pairs existing in a DNA database at once, while simultaneously checking a multitude of filtering constraints and validating primer specificity. Furthermore, MRPrimer suggests the best primer pair for each target sequence, based on a ranking method. Through qPCR analysis using 343 primer pairs and the corresponding sequencing and comparative analyses, we showed that the primer pairs designed by MRPrimer are very stable and effective for qPCR. In addition, MRPrimer is computationally efficient and scalable and therefore useful for quickly constructing an entire collection of feasible and valid primers for frequently updated databases like RefSeq. Furthermore, we suggest that MRPrimer can be utilized conveniently for experiments requiring primer design, especially real-time qPCR.
Identifying paediatric needs in cardiology and the prediction of sildenafil exposure in children with pulmonary arterial hypertension

Epidemiologische Studien uber den Off-Label-Gebrauch von Arzneimitteln bei Kindern sind wichtig, um Forschungsbedarf in padiatrischer Pharmakotherapie zu identifizieren. Dadurch kann der Fokus auf Arzneimittel gesetzt werden, die ohne wissenschaftliche Erkenntnisse bei kranken Kindern eingesetzt werden. Eine Off-Label-Verordnungsanalyse wurde von Januar bis Juni 2006 auf der Station fur Kardiologie und Pneumologie der Kinderklinik an der Universitat Dusseldorf durchgefuhrt. Daten der Patienten, deren Diagnosen und Arzneimittel wurden aufgenommen und mit der deutschen Fachinformation verglichen. Der Off-Label-Gebrauch wurde nach Altersgruppe, Dosis, Indikation und Applikationsweg des Arzneimittels ermittelt. Die Ergebnisse zeigten, dass 253 von 417 Patienten (61%) mindestens eine Off-Label-Verordnung erhielten. Insgesamt waren 553 von 1812 Verordnungen (31%) off-label. Die Herz-Kreislaufarzneistoffe besasen mit 129 von 216 Verordnungen (60%) den hochsten Off-Label-Anteil. Eine hohe Ubereinstimmung dieser Off-Label-Herz-Kreislaufarzneistoffe fand sich mit den Arzneistoffen, die von der European Medicines Agency (EMEA) gelistet wurden, um auf dringend erforderliche padiatrische Forschung aufmerksam zu machen. Ein beispielhafter Arzneistoff aus der Off-label-Liste der Herz-Kreislaufsubstanzen ist Sildenafil, bei dem vollig unzureichende Daten zur Pharmakokinetik bei Kindern vorliegen. Es war daher das Ziel im zweiten teil der Forschungsarbeit, ein Physiologie-basiertes Model zu entwickeln, um die Sildenafil Pharmakokinetik a priori in Kindern vorherzusagen als Grundlage fur zukunftige kindgerechte klinische Studien. Zunachst wurde dazu ein Erwachsenenmodel erstellt, welches dann auf Kinder skaliert wurde. Die simulierten Plasmakonzentrationen und PK-Parameter konnten in beiden Schritten die gemessenen Datenwerte adaquat darstellen. Die Ergebnisse der Simulation zeigten eine altersabhangige Exposition von Sildenafil: Kinder, die junger als 9 Jahre sind, benotigen hohere korpergewichtsnormierte Dosierungen von Sildenafil, um eine den alteren Kindern und Erwachsenen vergleichbare Exposition zu erzielen. Mit den Simulationen lassen sich auch altersspezifische Zeitpunkte fur die pharmakokinetischen Untersuchungen planen. Auf der Grundlage der Simulationen konnen demnach nun kinderspezifische Besonderheiten von Sildenafil in den klinischen Studien von vornherein berucksichtigt werden. Damit sollten die Studien einen hoheren Aussagewert erzielen konnen.
Artificial Stem Cell Niches

Stem cells are characterized by their dual ability to reproduce themselves (self‐renew) and specialize (differentiate), yielding a plethora of daughter cells that maintain and regenerate tissues. In contrast to their embryonic counterparts, adult stem cells retain their unique functions only if they are in intimate contact with an instructive microenvironment, termed stem cell niche. In these niches, stem cells integrate a complex array of molecular signals that, in concert with induced cell‐intrinsic regulatory networks, control their function and balance their numbers in response to physiologic demands. This progress report provides a perspective on how advanced materials technologies could be used (i) to engineer and systematically analyze specific aspects of functional stem cells niches in a controlled fashion in vitro and (ii) to target stem cell niches in vivo. Such “artificial niches” constitute potent tools for elucidating stem cell regulatory mechanisms with the capacity to directly impact the development of novel therapeutic strategies for tissue regeneration.
Characterization of MLSb resistance among Staphylococcus aureus and Staphylococcus epidermidis isolates carrying different SCCmec types

This work characterizes MLSb resistance in 39 methicillin‐resistant Staphylococcus aureus (MRSA) and 32 Staphylococcus epidermidis (MRSE) isolates. Of 21 erm(A) gene encoding MRSA isolates, 71.4% carried SCCmecIII, whereas of 12 isolates carrying the erm(C) gene, 83.3% carried SCCmecIV. Among the 25 MRSE isolates positive for the erm(C) gene, 80% had SCCmecIV or nontypeable cassettes. Isolates carrying these genes had MIC90≥ 256 μg/mL to erythromycin and clindamycin. The msr(A) gene was associated with a low MIC90 to these drugs. The erm(A) gene was associated with SCCmecIII in MRSA isolates, whereas the erm(C) gene was associated with SCCmecIV in both MRSA and MRSE isolates.