Urban beach closures due to coliform outbreaks have become disturbing signs of summer, yet water-testing technology has never been fast enough to keep up with changing conditions, nor accessible enough to check all waters.
Now, researchers at McMaster University have developed a rapid testing method using a simple paper strip that can detect E. coli in recreational water within minutes. The new tool can close the gap between outbreak and detection, improving public safety.
The new strips are coated with chemicals that react to the bacteria, and are printed using inkjet technology similar to that found in standard desktop printers. Within 30 minutes of sampling, the paper changes colour to indicate the presence of E. coli, with colours coded to represent different forms and concentrations of the bacteria.
Scientists from the Sentinel Bioactive Paper Network have created and validated the viability of the test strip, which can detect potentially harmful concentrations of E. coli in water quickly and simply, with much greater accuracy than existing portable technology.
The Natural Sciences and Engineering Research Council of Canada (NSERC) funds Sentinel, a strategic research network that spans the country and is based at McMaster. Several dozen researchers are involved in its initiatives.
‘Coliforms are always a big problem,’ said the paper’s lead author John Brennan, a McMaster chemistry professor who holds the Canada Research Chair in Bioanalytical Chemistry. ‘The methods used to detect outbreaks are slow, and tend not to be portable, as they often need a lab-based amplification step prior to testing, causing a time lag between an outbreak and a beach closure.’
Bioactive paper is both old and new, Brennan says. Since the late 1950s, physicians have been using bioactive paper to test for glucose in urine. In the last several years, the area has expanded quickly and research has become very competitive as scientists work on new applications.
‘It’s always a race,’ Brennan said.
In the future, the test strips should make it possible for consumers to check their water affordably and easily, without additional equipment, scientific knowledge or long waits.
‘One of the problems right now is that there is no simple, fast and cheap way to test recreational water, and certainly nothing out there in the realm of rapid tests for drinking water,’ Brennan said.
Field testing of the prototype strips is planned or under way in Canada and across the globe, in regions where untreated water poses particular health hazards. The results of these studies will help to refine the test strips and may lead to strips that are sensitive enough to tell whether water is safe enough to drink, said Brennan.
The standards for safe drinking water are hundreds of times tighter than those for safe swimming water. Typically, limits for safe swimming allow for a maximum of 100 to 500 cells of E. coli in 100 mL of water, depending on jurisdiction. For water to be considered safe for drinking, there cannot be even one cell in 100 mL – a little less than half a cup of water.
The next stage of pre-commercial development of the test strips is already funded by NSERC through a Phase I Idea to Innovation grant. Commercialization of a final product could take as little as two to three years. McMaster University

Mammalian spermatogenesis is maintained by spermatogonial stem cells (SSCs). However, since evidentiary assays and unequivocal markers are still missing in non-human primates and man, the identity of primate SSCs is unknown. In contrast, in the mouse, germ cell transplantation studies functionally demonstrated the presence of SSCs. LIN28 is an RNA-binding pluripotent stem cell factor, which is also strongly expressed in undifferentiated mouse spermatogonia. By contrast, two recent reports indicated that LIN28 is completely absent from adult human testes. Here, we analysed LIN28 expression in marmoset monkey (Callithrix jacchus) and human testes during development and adulthood and compared it with the mouse. In the marmoset, LIN28 was strongly expressed in migratory PGCs and gonocytes. Strikingly, we found a rare LIN28-positive subpopulation of spermatogonia also in the adult marmoset testis. This was corroborated by western blotting and quantitative RT-PCR. Importantly, in contrast to previous publications, we found LIN28-positive spermatogonia also in normal adult human and additional adult non-human primate testes. Some seasonal breeders exhibit a degenerated (involuted) germinal epithelium during their non-breeding season consisting only of Sertoli cells and SSCs. The latter re-initiate spermatogenesis prior to the next breeding-season. Fully involuted testes from a seasonal hamster and NHP (Lemur catta) exhibited numerous LIN28-positive spermatogonia, indicating a SSC-identity of the labeled cells. We conclude that LIN28 is differentially expressed in mouse and non-human primate spermatogonia and might be a marker for a rare SSC population in non-human primates and man. Further characterization of the LIN28-positive population is required. European Society of Human Reproduction and Embryology

Researchers at the Hospital de Mar Research Institute (IMIM) have discovered that the protein LOXL2 has a function within the cell nucleus thus far unknown. They have also described a new chemical reaction of this protein on histone H3 that would be involved in gene silencing, one of which would be involved in the progression of breast, larynx, lung and skin tumours.
Led by Dr Sandra Peiró, the study is a significant advance in describing the evolution of tumours and opens the door to researching new treatments that block their activity. ‘LOXL2’s action on the intra-cellular level and its interaction with histone H3 stimulates tumour growth. The fact that the protein LOXL2 is an enzyme and is overly expressed in many types of cancer makes it a very good therapeutic target. Now that we know how it acts, we need to keep working to develop chemical inhibitors that counteract its activity’, the researcher explained.
Previous studies had identified the extra-cellular function of the protein LOXL2, and it was being studied as a possible therapeutic target for avoiding metastasis in certain kinds of tumours. However, this study has described the presence of this protein at the level of the cell nucleus for the first time.
The process of gene expression in cells consists of transforming the information of the DNA into the proteins necessary to carry out different functions. The DNA molecule has been found to form a certain structure due to its interaction with some proteins called histones. When these histones are modified, the structure of the DNA is also modified and the final result is the expression or non-expression of a certain group of genes.
In the case of tumour cells, the protein LOXL2 acts upon one of these histones (histone H3) and modifies it, eliminating the lysine 4 amino group, a change never described before. As a result of its action, the genes modulated by histone H3, modified by LOXL2, stop expression, preventing the cells from behaving normally and favouring tumour development.
The work of Sandra Peiró’s team is the conclusion of three years of effort focused on the biochemical characterisation of the protein LOXL2 and the study of its role in the modification of histone H3. Since this modification had never been described before, the data obtained open many lines of research. The location on the genomic level of the protein LOXL2 and histone H3, modified by LOXL2, and the possible existence of some enzyme that might neutralise its function, are two of the questions that the group aims to tackle in the years to come. IMIM (Hospital del Mar Research Institute)

Low oxygen levels in cells may be a primary cause of uncontrollable tumour growth in some cancers, according to a new University of Georgia study. The authors’ findings run counter to widely accepted beliefs that genetic mutations are responsible for cancer growth.
If hypoxia, or low oxygen levels in cells, is proven to be a key driver of certain types of cancer, treatment plans for curing the malignant growth could change in significant ways, said Ying Xu, Regents-Georgia Research Alliance Eminent Scholar and professor of bioinformatics and computational biology in the Franklin College of Arts and Sciences.
The research team analysed samples of messenger RNA data-also called transcriptomic data-from seven different cancer types in a publicly available database. They found that long-term lack of oxygen in cells may be a key driver of cancer growth.
Previous studies have linked low oxygen levels in cells as a contributing factor in cancer development, but not as the driving force for cancer growth. High incidence rates of cancer around the world cannot be explained by chance genetic mutations alone, Xu said. He added that bioinformatics, which melds biology and computational science, has allowed researchers to see cancer in a new light. Gene-level mutations may give cancer cells a competitive edge over healthy cells, but the proposed new cancer growth model does not require the presence of common malfunctions such as a sudden proliferation of oncogenes, precursors to cancer cells.
‘Cancer drugs try to get to the root-at the molecular level-of a particular mutation, but the cancer often bypasses it,’ Xu said. ‘So we think that possibly genetic mutations may not be the main driver of cancer.’
Much of cancer research so far has focused on designing drug treatments that counteract genetic mutations associated with a particular type of cancer. In their study, the researchers analysed data downloaded from the Stanford Microarray Database via a software program to detect abnormal gene expression patterns in seven cancers: breast, kidney, liver, lung, ovary, pancreatic and stomach. The online database allows scientists to examine information from microarray chips, which are small glass slides containing large amounts of gene material.
Xu relied on the gene HIF1A as a biomarker of the amount of molecular oxygen in a cell. All seven cancers showed increasing amounts of HIF1A, indicating decreasing oxygen levels in the cancer cells.
Low oxygen levels in a cell interrupt the activity of oxidative phosphorylation, a term for the highly efficient way that cells normally use to convert food to energy. As oxygen decreases, the cells switch to glycolysis to produce their energy units, called ATP. Glycolysis is a drastically less efficient way to obtain energy, and so the cancer cells must work even harder to obtain even more food, specifically glucose, to survive. When oxygen levels dip dangerously low, angiogenesis, or the process of creating new blood vessels, begins. The new blood vessels provide fresh oxygen, thus improving oxygen levels in the cell and tumour and slowing the cancer growth-but only temporarily.
‘When a cancer cell gets more food, it grows; this makes the tumour biomass bigger and even more hypoxic. In turn, the energy-conversion efficiency goes further down, making the cells even more hungry and triggering the cells to get more food from blood circulation, creating a vicious cycle. This could be a key driver of cancer,’ Xu said.
Xu explained that this new cancer-growth model could help explain why many cancers become drug resistant so quickly-often within three to six months. He stressed the importance of testing the new model through future experimental cancer research. If the model holds, researchers will need to search for methods to prevent hypoxia in cells in the first place, which could result in a sea change in cancer treatment. University of Georgia

A race to unlock genetic clues behind living to 100 is set to begin next year, after a US team announced it will compete for the $10m Genomics X Prize. Genetic entrepreneur Dr Jonathan Rothberg is entering the challenge to identify genes linked to a long, healthy life. His team – and any other contenders – will be given 30 days to work out the full DNA code of 100 centenarians at a cost of no more than $1,000 per genome.
The race will start in September 2013. Under the rules of the Archon Genomics X Prize, teams have until next May to register for the competition. Dr Rothberg’s team from Life Technologies Corporation in California is the first to formally enter the race.
His latest business venture, Ion Torrent, makes the Personal Genome Machine and the Ion Proton sequencer
Rothberg claims his machines can sequence DNA more quickly and cheaply than ever thought possible
The Ion Proton sequencer will be used for the challenge. Being able to sequence the full human genome at a cost of $1,000 or less is regarded as a milestone in science.
It is seen as the threshold at which DNA sequencing technology becomes cheap enough to be used widely in medicine, helping in diagnosis and in matching drugs to a patient’s genetic make-up.
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One hundred people aged 100 have donated their DNA for the project.
Scientists believe people who reach a very old age may have certain rare changes in their genes which protect against common diseases of later life, such as heart disease and cancer. If these genes can be identified by analysing the DNA codes of centenarians, it will help scientists search for new medical treatments and perhaps ways to prolong life. However, many sample DNA sequences will be needed in order to get the accuracy needed to pinpoint changes on the scale of a few genetic letters among the three billion in the human genome.
Dr Jonathan Rothberg, a geneticist and entrepreneur, said the DNA of 100 centenarians is a good start towards finding ‘the fountains of youth’.
He told BBC News: ‘One hundred people will give you a hint. One thousand will make you reasonably sure. Ten thousand will let you say, ‘Hey, these are the genes involved in cancer or heart disease”.
Dr Craig Venter is the originator of the prize and one of the main players in the race to sequence the first human genome, which was completed in 2003. BBC