LIMS and stem cell research

LIMS is an acronym for Laboratory Information Management Software, is a common software used in environmental, pharmaceutical and research institutions. It’s a software to manage laboratory life, indeed with this tool it’s possible not only to manage samples and standards, users and instruments, but also to send invoices, control the automation of the workflow, manage projects. The current goal is to retain result achievement, elaboration, further decision and final review directly at the workplace, and not in the office. Indeed, all laboratory users can login and use this software, projects are organized by type, subtype, priority and other criteria and all information related are recorded within; moreover, also instruments can send data directly to LIMS that is configured to guarantee the traceability of the work. With LIMS it’s possible to save time and money and improve rate and productivity: indeed, big inventories could be reduced or eliminated at all and researchers don’t waste too much time to search data of previous experiments and so on.

Stem cell research is an exciting branch of science that quickly advances and provides data. In order to manage these data and facilitate the collaboration between institutions it could be reasonable the use of LIMS in the most upgraded version. The first feature that the software should have is to be user friendly because in one laboratory researchers could have different background and this difference could be more significant in more laboratories during a collaboration. In order to communicate results or change samples or make common decisions, a software like LIMS 247 used in all labs could help to coordinate the work. Many techniques and protocols can be applied in stem cell research, from cellular biology to molecular biology to biochemistry; the use of special software, directly configured by researchers, can help to record workflows and data and trace them: this is the second important feature of a software that should be used in stem cell research. Progress reports are also important during laboratory life, LIMS guarantees a secure mechanism for data reporting, always checked by the quality control system present in the software. We have presented one possible application of LIMS in research laboratories, but this software could be successfully employed also for the management of cell cultures and patients samples collected in hospitals. Again, to perfectly recorded every information about each sample -and when we work with patients the perfection is a must- it’s possible to use LIMS. This software can help researchers to maintain the traceability of the samples and clinicians that can base their decisions on scientific data from the same samples. This process could improve the results from regenerative medicine, in the case of stem cell research, but in all clinician departments could give a great hand. Modern science, specially stem cell research that is the future for medicine and biology, cannot exclude informational tools from its life: software like LIMS 247 from RURO Inc. could improve the quality of scientific works and increase the data and publications productivity and the quality of the clinical services for patients.

New guidelines for stem cells research

Stem cells have implications in numerous diseases or congenital defects; studying this kind of cells will allow us to understand important biological mechanism and care for instance cancer, neurological problems and so on. Several ethical issues are related to stem cells research, in particular to embryonic stem cells, and public debate has often limited the advance of science in this field.

In March 2009, US president B. Obama changes the policy about stem cells in respect of his predecessor G.W. Bush and revokes the limitations for federal funding for research involving human embryonic stem cells. The National Institute of Health (NIH) supports actions that lead to exploration of human stem cells and show great benefits for the whole humankind. Secretary reviews the existing NIH guidelines and writes new guidance for scientists involved in stem cell research. All these documents allow to simplify procedures for funding stem cells research and guarantee the governmental agreement towards new discoveries and new applications in this field. Stem cells research represents a great challenge for next generation of scientists and an hope for patients affected by serious diseases, such as cancer. It’s also important to remember that a long way has to be performed to obtain clinically relevant results.

Computational tool to measure angiogenesis

Computational analysis is an important tool in biology and medicine. Recently, a group of the National Research Council of Milan (Italy) proposed one new approach to study vessel distribution based on the quantification of functional microvessels. By using in vivo staining with sulfosuccinimidyl-6-(biotinamido) hexanoate, they determined the number of microvessels.

Then, they used pixel dilatation of digital images, by computing the number of dilatation cycles needed to permeate a pre-defined amount in each image (Halo index). In this way, researchers could evaluate the number of new microvessels or otherwise the decrease of vascularization after pharmacological treatment. Indeed, they validated the method by administering Sorafenib –anti-angiogenetic molecule- or placebo to mice carrying tumors and compared the images from these two models. They determined the Halo index for each group of animals and showed a statistically difference between Sorafenib- treated samples and controls, as expected. The most important aspect of this kind of analysis was the normalization of the area to check, in order to compare several hundred of images that showed different amounts of vascular tissue. This study allowed to better determine the activity of drug in respect of angiogenesis and vascular modifications. In general, it could be also a useful diagnostic tool for the follow up of anti-cancer therapies.

Nanog and pluripotency

In August 2009 Cell journal published an important article about the role of Nanog in pluripotency. Silva and colleagues showed that Nanog played a crucial role in development of pluripotency in mice. Indeed, they generated a KO mouse for nanog gene and they observed a block in reprogramming cells to achieve the full pluripotency; Nanog re-expression allowed the complete restoration of the reprogramming process indicating the central role of this protein in the acquisition of pluripotency.

Researchers were not able to obtain embryonic stem cell culture from nanog null mice because the embryos didn’t form the inner cell mass and so the pluripotent compartment. Molecular explanation of the role of Nanog is probably related to the signalling pathway that involves also Oct4, it seems that Nanog is important to sustain that pathway by inducing a self maintenance of the system. Nanog is also important for the reactivation of chromosome X, another crucial step to reach the pluripotency. This work increases our knowledge to obtain the induction of pluripotency in vitro: this goal is crucial for instance for many applications of regenerative medicine. Defining the factors that control, start and maintain pluripotency will help us to obtain safer and better induced pluripotent stem cell cultures.

Stem cells nomenclature

Stem cells appellation derives from German Stammzelle that defines firstly the evolutionary unicellular ancestor of multicellular organisms and secondarily the ancestral stem cell in an organism, initially in the germ line. Subsequently this term was applied to other tissues, generating some confusion.

In particular some problems arise with the notions of precursor and progenitor: indeed we talk about progenitor if the appellation of stem cells leaves doubts about the nature of the cells, while precursor is usually used to define the ancestral embryonic cell in the lineage of interest –for instance blasts are precursors of neuroblast, myoblast and so on- General and frequently accepted criteria to define one stem cell are the self renewal and the transit amplification; another criterion that has been proposed is the classification of cell states in terms of epigenetic, chromatin rearrangement and gene- expression. In this way it could be possible to distinguish stem cell from progenitor and precursor without nomenclature bias. Also the assumption that in one tissue only one stem cell is present, could be corrected and when cell stem signature will be done, it could be possible –and reasonable- to identify different stem cells with different genetic signatures.

Nanoparticles as a novel class of anti-bacterial

Anti-bacterial drug often acts by disrupting the double layer of cellular membrane that is negatively charged. These molecules contain positive groups and an hydrophobic core, important to insert into the membrane. In order to specifically overcome the blood brain barrier and reach the brain, some researchers of the University of Singapore studied a novel particle constituting of an hydrophobic core and a strain of positively charged arginine. Tat sequence, derived from HIV virus, was used to vehicle the molecule over the blood brain barrier because TAT protein mediates the passage of proteins across the endothelial cells.

Furthermore, cholesterol was added to increase the capability to penetrate into the membrane and to concentrate the active peptide. So, the final structure of this peptide nanoparticle is Cholesterol- 3 glycine, as a spacer- 6 arginine- TAT protein. In vitro, this peptide killed fungi, bacteria and yeast and showed an important activity also in vivo in rabbit infected with S. Aureus, meningitis’s vector, by overcoming the blood brain barrier. This study opens new perspectives on nanoparticle engineering that could be applied in a broad range of diseases: for instance in cancer or in other situation in which is crucial to target a specific type of cells.

Smoking behavior is genetically determined?

Drug addiction is usually genetically determined by peculiar single nucleotide polymorphism. These mutations are clustered and associated to more frequent form of dependence. Given the status of smoking behavior that is often considered as a drug, scientists from the University of Missouri analyzed SNPs in large Caucasian population. They identified nine loci where the mutations of SNP were located. Furthermore, in African population they observed other two SNPs different from the first none above.

All these single nucleotide polymorphism’s were identified near to IL15 gene and were correlated with high parameters currently used to evaluate nicotine dependence. Male specificity was observed in both populations analyzed. IL15 is an important cytokine that controls the immune system and, in this case, seems strongly associated also with smoking habit. The molecular mechanism that SNPs use seemed to be related to gene regulation and expression because the most of mutations were identified in the binding site for transcription factors. Smoking is one of principal risk factor for lung cancer, so the determination of SNPs that could influence this behavior could allow to identify potential smokers into the population and, maybe, avoid that they start to smoke. This approach could decrease the number of smokers and, potentially, of lung cancer patients.

Telomeres

Telomeres are DNA portions, particularly rich in guanine, that protect the end of chromosomes and avoid chromosome fusion and other genetic alterations that could compromise cellular life. In tissue, shortened telomeres can cause problems to injury repair and an acceleration of ageing. Furthermore, short telomeres are associated to cancer predisposition, bone marrow failure and pulmonary fibrosis These functions of telomeres, as a tumor suppressor, have been identified in mammals and in other animals with a long life span while this mechanism doesn’t exist in short-lived organisms.

In several studies about familial heritance of telomeres abnormalities, it has been demonstrated that haplo-insufficiency of telomeres can determine a broad range of diseases, often different between members of the same family. This could mean that phenotype of human heritable telomerase deficiencies is influenced by additional environmental, stochastic and genetic factors: a Darwinian explanation of the role of telomeres has been proposed in July 2009 in the Embo Journal. This new perspective could be useful to explain what happens in stem cells that can be submitted to several stimuli to differentiation or replication and loss the ability of self renewal. Otherwise in cancer epidemiology it could be useful to identify the factors above to better explain cancer susceptibility linked to telomere and telomerase activity.

Critical points of medical writing

An important part of clinical studies is often associated to write report, analyze data and do statistics. Commercial software are now available to facilitate data collection and management and the collaboration between institutions, but one difficult work still be the elaboration of the results and the creation of final report to be presented to approval committees. Thus, medical writing department assumes crucial role in a pharmaceutical company. This department must be organized in order to efficiently accomplish the production of promotional materials, documentation for marketing new products and manuscript for publication. Medical writing follows specific guidelines to guarantee scientific correctness and ethical standards. Indeed, results reported in papers, reviews and brochures must be rigorous, transparent and consistent; the writing must be comprehensible, accurate, concise and logically organized, all the assertions must be justified and proper terminology facilitates the proficiency. Medical and nursing professionals often don’t have time or inclination to write their papers, as well as in pharmaceutical companies results from unsuccessful clinical studies are not published again because of lack of time.

It’s astonishing that a large percentage of works presented in national meetings doesn’t proceed to publication in peer review journal. In this way the advances of science are avoided. Fortunately, professional medical writers can supply the important service to write papers and reviews and make these data available to scientific community. Medical writer are often ghost- writer and their name doesn’t appear between authors in the final publication, even if now a task force of European medical writer association (EMWA) tries to solve this problem. For transparency, indeed, the reader should always know about the presence of a ghost-writer and also the name “ghost-writer” itself is misleading; EMWA task force suggests the use of a more neutral term. Anyway, medical writing still stimulating and interesting work, because allows to enter in direct contact with clinical researchers and know results of studies before the publication itself. Not only physicians and scientists must be responsible of data truth, but also medical writer must learn about ethical practice: in this way, papers are really scientifically correct and scientific literature continues to have a significance. Furthermore, founding and grant achievement are often associated to the number and quality of publication of the principal investigator, so writing numerous papers represents an opportunity also to obtain financial advantages, rather than scientific. Publishing results allows to receive feedback about your study and useful suggestion for future perspectives and, in some cases, to create a network of common interest with other groups that work at the same topic. In conclusion, medical writing is one new aspect of scientific and pharmaceutical life that guarantees success of studies, but also could be considered a new profession with specific rules, aims and challenges.

Pandemic distribution of H1N1 influenza vaccine

In previous post, we talked about H1N1 virus flu that could be defined as pandemic. In June 2009, the director general of World Health Organization declared that influenza A pandemic reached the phase 6, so the virus was diffused on global scale. From June to now, great efforts have been done by pharmaceutical companies to set up a vaccine and produce it in really high amount in order to satisfy the global need. Several problems will be encountered when vaccine will have to be sold and distributed.

Firstly, rich and poor countries have the same necessity for this vaccine, but of course different financial availability. It could be important that regulatory office will allow an equal and fair distribution of the vaccine and that rich countries will contribute to cover costs also for poor countries. Secondarily, mass vaccination campaign will have to be organized to reach most of the population: in this case poor countries are facilitated because other campaigns, for instance versus malaria or polio, are now in progress, while rich countries need to start from the beginning. Last but not least, it’s important to consider if we are ready to face this flu and if manufacturers can produce enough vaccine for all people. We hope that vaccine will be available for all at the moment of the crisis.