Even tiny amounts of viruses can have disastrous consequences. RNA identification can reveal the type of virus present. A fast and sensitive technique based on optical detection has now been outlined. Scientists from Germany and Finland have demonstrated the binding of an RNA target to a probe made of gold nanorods and a DNA origami structure. Chirality switches triggered by binding can be measured by circular dichroism spectroscopy.
Identifying the pathogen-often a virus-that is troubling a patient is among the biggest challenges in healthcare. Viruses responsible for Zika fever, AIDS, and hepatitis C contain mutating RNA sequences. Physicians need to know quickly which type of virus their patients have acquired, but current techniques based on multiplying RNA are costly and time-consuming. Now, Tim Liedl from Ludwigs-Maximilians-Universität in Munich, Germany, and his colleagues, have developed a fast detection strategy based on nanoplasmonics, DNA origami, and an optical readout.
Light can induce plasmonic waves in nanosized metal structures smaller than the wavelength of the incident light. This resonance may lead to strongly enhanced light emission even from nanoscopic structures-a feature that is highly interesting for biosensing applications. Liedl and colleagues have created a nanosized sensing probe for RNA molecules.
The probe, a nanosized apparatus made of DNA and gold nanorods, was assembled by the so-called DNA origami technique, which exploits the specific interactions of the DNA bases to fold and glue together single strands in any desired form. The authors constructed two bars of parallel DNA helices loosely connected through a hinge in the middle of the bars. Gold nanorods were placed on top of each of the crossed bars. Both crossing arms were supplied with functionality at their ends: the scientists attached one single DNA sequence complemented with a blocking strand to one arm, and the complementing DNA sequence to the other. In the presence of target RNA, which could be a typical viral RNA sequence, the blocking strand would leave its DNA in favour of RNA hybridization, and both single DNA sequences would complementarily form a double strand whereby the two arms of the cross are pulled together. This structural change introduces chirality to the probe.
Chirality can be detected with circular dichroism. And indeed, the structural changes triggered by the RNA binding induced a circular dichroism signal detectable with a CD spectrometer. Concentrations as low as 100 picomolar of the target RNA were recognized, according to the authors. The scientists hope to establish this technique in lab-on-a-chip systems where few steps are required for sample preparation and low-cost miniature devices lead to sensitive results. Preliminary results on serum from blood with added viral RNA were promising.
The authors admit that the detection limits are still not low enough to be clinically relevant. However, they believe improvements should be possible; including, better protection of the nanosensors from serum proteins, a change to better resonating plasmonic metals, and expansion of RNA recognition sites. This could make the technique a promising diagnostic tool that is not necessarily limited to viral RNA.

MarketScreenerwww.marketscreener.com/news/Viral-RNA-Sensing-Optical-detection-of-picomolar-concentrations-of-RNA-using-switches-in-plasmonic–27285028/

Rheumatoid arthritis (RA) is an autoimmune disorder that occurs when the immune system mistakenly attacks the body’s tissues. Unlike the wear-and-tear damage of osteoarthritis, rheumatoid arthritis affects the lining of the joints, causing painful swelling that can eventually result in bone erosion and joint deformity.
Most RA patients are positive for anticitrullinated protein antibodies (ACPA), and these antibodies are highly specific for RA diagnosis. ACPA recognizes various citrullinated proteins, such as fibrinogen, vimentin and glucose- 6-phosphate isomerase. Citrullinated proteins are proteins that have the amino acid arginine converted into the citrulline, which is not one of the 20 standard amino acids encoded by DNA in the genetic code. Autoreactivity to citrullinated protein may increase susceptibility to RA.
While many candidate citrullinated antigens have been identified in RA joints, the involvement of citrullinated proteins in blood serum remains mostly uninvestigated. To that end, a team of University of Tsukuba-centred researchers set out to explore the expression and commonality of citrullinated proteins in peptide glucose-6-phosphate isomerase-induced arthritis (pGIA) and patients with RA, and went one step further to investigate its correlation with RA disease activity.
“We examined serum citrullinated proteins from pGIA by western blotting, and the sequence was identified by mass spectrometry. With the same methods, serum citrullinated proteins were analysed in patients with RA, primary Sjögren’s syndrome, systemic lupus erythematosus, and osteoarthritis as well as in healthy subjects,” study corresponding author Isao Matsumoto explains. “In patients with RA, the relationship between the expression of the identified protein inter-alpha-trypsin inhibitor heavy chain 4 (ITIH4) and clinical features was also evaluated, and the levels of citrullinated ITIH4 were compared before and after biological treatment.”
The researchers found that citrullinated ITIH4 was highly specific to patients with RA, compared with patients with other autoimmune and arthritic diseases or in healthy subjects, indicating a potential role for citrullinated ITIH4 in RA pathogenesis. Notably, its levels were decreased in correlation with the reduction of disease activity score after effective treatment in patients with RA. Moreover, antibody response to citrullinated epitope in ITIH4 was specifically observed in patients with RA.
“Our results suggest that citrullinated ITIH4 might be a novel biomarker to distinguish RA from other rheumatic diseases and for assessing disease activity in patients with RA,” Matsumoto says. “To our knowledge, this is the first report of its kind in the literature.”

MedicalXpresshttps://medicalxpress.com

An international team of researchers from the Hopp Children’s Cancer Centre at the NCT Heidelberg (KiTZ), the European Molecular Biology Laboratory (EMBL) and the German Cancer Consortium (DKTK) together with colleagues at the St. Jude Children’s Research Hospital in Memphis and the Hospital for Sick Children in Toronto has summarized hereditary gene defects which can trigger the development of certain malignant brain tumours (medulloblastoma). From their findings, the team has derived recommendations for routine genetic screening in medulloblastoma patients. Medulloblastoma is a rare malignant tumour of the cerebellum and occurs predominantly in children. Scientists believe that in many cases hereditary gene defects trigger the development of this malignant disease. However, there are no standards for routine genetic screening of patients, nor are there guidelines and a corresponding nationwide infrastructure for genetic counselling of affected families.
Scientists have now been able to characterize medulloblastoma more accurately and to derive recommendations for genetic testing based on analysis of 1022 patients with medulloblastoma. “We analysed genes that have been previously implicated in predisposition to any type of pediatric and adult cancer”, says Sebastian Waszak from the EMBL Heidelberg who is one of the study’s lead authors. It turned out that six genes were also frequently affected by genetic alterations in patients with medulloblastoma.
Considering the six significantly enriched genes, about five percent of patients had an increased risk of cancer. Taking into account all cancer risk genes, about eleven percent of the patients had an increased cancer risk. Looking at a particular tumour subgroup, the so called “SHH-activated medulloblastoma”, even 20 percent were identified to harbour a genetic predisposition to cancer.
These predisposing mutations occur in every single cell of the patient and can be also passed on to offspring. “Mutations of this kind often indicate a familial predisposition to cancer and therefore place special demands on the treatment of patients and the counselling of families”, said Paul Northcott from the St. Jude Children’s Research Hospital in Memphis, who shares the lead authorship. The results are particularly important because both materials from previous studies and patient data from four current or recently completed clinical trials were included in the analysis.
Based on these findings and other tumour features, the scientists developed criteria for routine genetic screening. “Hereditary disease factors usually have a significant impact on the whole family of the patient, We want to make genetic analysis available as a standard of care for patients with specific medulloblastoma”, says Stefan Pfister, KiTZ director, scientist at the German Cancer Research Centre, and senior physician at the Heidelberg University Hospital. To make this possible, Stefan Pfister and Christian Kratz from the Hannover Medical School have created a registry for patients with a hereditary cancer predisposition and a website that contains information for patients, families, and physicians (www.krebs-praedisposition.de).

The German Cancer Research Center (DKFZ)https://tinyurl.com/ya5akv4j

The longest FlexLab automation system ever produced by Inpeco has been designed for a mega volume reference laboratory customer, Hermes Pardini group based in Minas Gerais, Brazil. Siemens Healthineers (Inpeco’s strategic automation partner who sold the solution) is implementing the FlexLab system for Hermes Pardini’s “Enterprise” project, which will result in the largest laboratory automation platform in the world, linking more than 100 analyzers and 7 clinical specialties.
The Hermes Pardini Group is highly innovative in diagnostics medicine, and will handle 110 million sample tubes every year to address diagnostic testing needs of patients and healthcare providers from all across Brazil. The Enterprise project is expected to be operating at its full capacity in 2019, and will automate the distribution of sample tubes to nearly 100 different analyzers with a total length of 330 meters, which will include more than 70 pre- and postanalytical modules to eliminate the need for error-prone and time-consuming manual interventions within the clinical laboratory. It is to be installed in the Vespasiano site (Belo Horizonte area) in the current laboratory testing area (3,500 square meters of floor space).
“Unlike conventional laboratory set-ups, where sample tubes must be moved manually between different analyzers, our enterprise lab will employ a ‘one-touch, one workflow’ concept to eliminate the need for manual interventions, ensure sample traceability, and reduce the turnaround time to results,” said Guilherme Collares, Chief Operations Officer of the Hermes Pardini Group.
Inpeco’s High Throughput FlexLab solution will contribute to make this concept a reality, and enable providers to receive results faster, thereby enabling better patient care. The project also includes refrigerated storage units, with capacity to hold more than 1.3 million samples, and a newly developed advanced vision system, which is able to detect sample deterioration such as hemolysis, icterus or lipemia. “We’ve been in touch with Hermes Pardini since they began 2 evaluating options to replace the automation system they were using – said Andrea Pedrazzini, President of Inpeco – and we are extremely proud and pleased that such a prestigious institution has decided to adopt the largest FlexLab system ever built to fully automate their samples process, from loading to storing and disposing.”

http://www.inpeco.com/en/

A multidisciplinary team at NUS BIGHEART has developed enVision – a portable, easy-to-use and inexpensive device for quick and accurate screening of diseases.
enVision takes between 30 minutes to one hour to detect the presence of diseases, which is two to four times faster than existing infection diagnostics methods. In addition, each test kit costs under S$1 – 100 times lower than the current cost of conducting similar tests.
“The enVision platform is extremely sensitive, accurate, fast, and low-cost. It works at room temperature and does not require heaters or special pumps, making it very portable. With this invention, tests can be done at the point-of-care, for instance in community clinics or hospital wards, so that disease monitoring or treatment can be administered in a timely manner to achieve better health outcomes,” said team leader Assistant Professor Shao Huilin from the Biomedical Institute for Global Health Research and Technology (BIGHEART) and Department of Biomedical Engineering at NUS. Asst Prof Shao is also an investigator with the Institute of Molecular and Cell Biology (IMCB) under the Agency for Science, Technology and Research (A*STAR).
The research team used the human papillomavirus (HPV), the key cause of cervical cancer, as a clinical model to validate the performance of enVision. In comparison to clinical gold standard, this novel technology has demonstrated superior sensitivity and specificity.
“enVision is not only able to accurately detect different subtypes of the same disease, it is also able to spot differences within a specific subtype of a given disease to identify previously undetectable infections," Asst Prof Shao added.
In addition, test results are easily visible – the assay turns from colourless to brown if a disease is present – and could also be further analysed using a smartphone for quantitative assessment of the amount of pathogen present. This makes enVision an ideal solution for personal healthcare and telemedicine.
“Conventional technologies – such as tests that rely on polymerase chain reaction to amplify and detect specific DNA molecules – require bulky and expensive equipment, as well as trained personnel to operate these machines. With enVision, we are essentially bringing the clinical laboratory to the patient. Minimal training is needed to administer the ,test and interpret the results, so more patients can have access to effective, lab-quality diagnostics that will substantially improve the quality of care and treatment,” said Dr Nicholas Ho, a researcher from NUS BIGHEART and A*STAR’s IMCB, and co-first author of the study.

National University of Singapore
news.nus.edu.sg/press-releases/envision-device-for-disease-screening