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Ars Biotech, Largo di Torre Argentina 11, Rome (2026)

04/01/2021

Did you know that the risk of harmful mutations in children is due more to the age of the father than to the age of the mother? 👶🏻🧬

Most mutations arise as a result of unpaired chromosomes errors. However, the number of human male germ-cell divisions greatly outnumbers female germ-cell divisions.
Because each mitotic cell division is preceded by DNA replication, the male germ-line mutation rate might be expected to greatly exceed the female germ-line rate.
The journey from the human zygote of the mother to her primary oocyte requires approximately 31 cell divisions.
In males, by contrast, 34 cell divisions are required for germ-cell development before s***matogenesis; Then, after puberty, s***m cells are continuously produced every 16 days, that is 23 cell divisions per year. A further 4 cell divisions are required for the differentiation.
If we take an average age of onset of male puberty as 13 years old and an average paternal age of 30 years, a total of 34 + (23 x (30-13)) + 4 = 429 male germ-cell divisions are needed.
Even more germ-cell divisions would be required to produce s***m in older fathers.

In many studies, the observed rates of de novo single nucleotide variants in families show that the male germ-line mutation rate exceeds the female mutation rate by a factor of about 4, but is dependent on the paternal age.

A maternal age effect has also recently become evident in a large study, thus, a 40-year-old mother would be expected to contribute 5 more de novo mutations to her child than she would have done at age 20, and a 40-years-old father should contribute 20 additional mutations than when aged 20 years

31/12/2020

Time to take stock of the situation 🦠🔬

20/10/2020

p53, guardian of the genome🧬⚔️

p53 is the most known onco-suppressor, mutated in 40% of all solid tumour, it is “the guardian of the genome” because it’s activated by a lot of stress stimuli, including DNA damages, oxidative stress and hyperproliferative stimuli.
Missense mutations in the TP53, the gene which codifies for P53, are extremely widespread in human cancers and give rise to mutant p53 proteins that lose tumor suppressive activities, Cancer cells acquire selective advantages by retaining mutant forms of the protein, which radically subvert the nature of the p53 pathway by promoting invasion, metastasis and chemoresistance.
P53 can regulate the cell cycle, this is the most important function, he can incredibly rapidly block the cell cycle progression, either in G1-S and G2-M. Then it induces DNA repair mechanism stimulation, or better the production of transcription factors for DNA repair mechanism. Then in case there is nothing to do, it activates apoptosis.
But not only that, it also inhibits metabolic reprogramming, de-differentiation and invasion/metastasis capability.
In normal conditions, p53 translation levels in the cell would be sufficient to impair proliferation, eventually causing apoptosis, so it is expressed but is mostly bound to MDM2/4 complex, which keeps it inactive and ubiquitinated it, leading p53 to the proteasome degradation.
In case of DNA damages, as of other stimuli, (this activates ATM/ATR that phosphorylate MDM2 and MDM4 which are ubiquitinated releasing p53 from the complex, so that) p53 can go performing its activity.
Clearly, the variety of TP53 missense mutations produces distinct functional consequences, thus tumor vulnerabilities may differ based on the specific TP53 mutation, as well as on the tumor type. Much study is still required to define these aspects, moreover multi-mutant, multi-omic approaches could provide a clearer perspective on the range of mutp53 cancer-protecting activities, and their prevalence in different mutp53 variants and in different tumor contexts, helping to identify “core” mutp53 activities as ideal therapeutic targets.

14/10/2020

Gene Therapy, the future of personalized medicine 🧬💉

Gene Therapy is an experimental technique that uses genes to treat or prevent disease. Over the past three decades, the field of Gene Therapy has made significant strides toward the treatment of previously untreatable disorders as Cancer, infectious, cardiovascular neurological and monogenic diseases.
This facility is allowing researchers to test several different approaches:

-Replacing a mutated gene that causes disease with a healthy copy of the gene
-Inactivating or “knocking out” a mutated gene that is functioning improperly.
-Introducing a new gene into the body to help fight a disease.

While there have been numerous targets of gene therapy trials, only four therapies have reached FDA and/or EMA approval for clinical use, particularly because of the riskiness and efficacy of it. One of the major obstacles has been the delivery of genes to the appropriate cell, tissue, and organ, introducing a gene into the brain with trillions of cells, or the liver with billions of cells, or the rare hematopoietic adult stem cell that has the potential to populate all lineages of lymphoid and myeloid cells. Much effort has been devoted to finding ways to efficiently deliver a therapeutic gene to the desired cell type, resulting in sustained production of the gene product, ideally through the entire life of the recipient, without unwanted side effects like genotoxicity or unsettling the immune balance.
Furthermore gene correction using CRISPR-Cas9 is an extension of gene therapy that has received considerable attention in recent years and boasts many possible uses beyond classical gene therapy approaches.
To sum up, Gene Therapy is a promising treatment option for a number of diseases including inherited disorders, some types of cancer and certain viral infection.
Where will the development of this sophisticated therapy take us?
Write it in the comments

12/10/2020

How the diagnostic test for Covid-19 works? 🧬🔬🦠

PCR, or polymerase chain reaction tests the virus’s genetic material in the body, this is useful to diagnose who is currently affected.
PCR, maybe it’d be better to say “Real Time PCR” is used to amplify genetic information into a large amount for being able to observe it.
To develop a covid-19 test, researchers need to sequence the genome of SARS-CoV-2, in order to identify regions that are unique and then target these particular segments.
First of all, it’s necessary to collect a sample, blood for hepatitis virus, f***s for poliovirus and samples from nose and throat for coronavirus.
Secondly, the genetic information of SARS-CoV-2, an RNA strand, must be reverse transcribed to cDNA, a strand of complementary DNA, in order to compare with the sample DNA.
The RT-PCR test begins, the 2 genomes (human and virus) and other factors are inserted to make the reaction possible, if the virus is present in the sample, it’s unique regions of genetic code will be identify and copied thanks to complementary primers, which, in synergy with other components and enzymes will allow the reaction.
Finally, one strand of virus cDNA becomes hundreds of million, and we would be able to determine it thanks to the fluorescence resulting from the action of enzymes, whether the PCR machine senses fluorescence signal, the sample has tested positive for the virus, meaning the individual is infected.

16/06/2020

The Future of Antibiotics and Resistance 🦠🧫
Today, the greatest risk to human health comes in the form of antibiotic-resistant bacteria. We live in a bacterial world where we will never be able to stay ahead of the mutation curve.
In its recent annual report on global risks, the World Economic Forum underscores the facts that antibiotic resistance and the collapse of the antibiotic research- and-development pipeline continue to worsen despite our ongoing efforts on all these fronts.
If we’re to develop countermeasures that have lasting effects, new ideas that complement traditional approaches will be needed.
On the other hand, Prokaryotes (bacteria) “invented” antibiotics billions of years ago, and resistance is primarily the result of bacterial adaptation to eons of antibiotic exposure.
First, in addition to antibiotics’ curative power, their use naturally selects for preexisting resistant populations of bacteria in nature. Second, it is not just “inappropriate” antibiotic use that selects for resistance. Rather, the speed with which resistance spreads is driven by microbial exposure to all antibiotics, whether appropriately prescribed or not.
Thus, even if all inappropriate antibiotic use were eliminated, antibiotic-resistant infections would still occur (albeit at lower frequency).
Third, after billions of years of evolution, microbes have most likely invented antibiotics against every biochemical target that can be attacked and, of necessity, developed resistance mechanisms to protect all those biochemical targets.
Indeed, widespread antibiotic resistance was recently discovered among bacteria found in underground caves that had been geologically isolated from the surface of the planet for 4 million years. Remarkably, resistance was found even to synthetic antibiotics that did not exist on earth until the 20th century. These results underscore a critical reality: antibiotic resistance already exists, widely disseminated in nature, to drugs we have not yet invented.
Promising future strategies to combat resistance can be divided into five categories, each of which requires additional societal investment in basic and applied research and policy activities.

11/06/2020

Endocrine disrupters and reproductive health 🦠 🎀
Endocrine disrupters are among the main factors for the onset of diseases with high social and economic impact, such as changes in reproductive and sexual health as well as various other diseases, such as diabetes and obesity, which may have an indirect impact on these conditions. Multidisciplinary action is needed to try to reduce the impact of these substances in order to improve the quality of life and the well-being of individuals and society. The alarming increase in pair infertility is linked to a series of economic, social and cultural phenomena that occurred in the last century, which led to a real revolution in the daily rhythms, significantly affecting the frequency and quality of sexual in*******se.
To all this has been added in the last 50 years a progressive reduction in the quality of the seminal fluid. This worrying worsening of the reproductive potential of the human being is partly due to the presence of pervasive and resistant environmental contaminants such as endocrine disrupters, exogenous chemical elements deriving from industrial productions, Insecticides, fungicides and herbicides, which mimic hormonal activity, undermining general health and endocrine and reproductive activity. These harmful substances are mainly present in industrialized countries in the air, in water and in many foods or objects of daily use.

05/06/2020

Transposable Elements and their great evolutionary value 🧬🔬
Transposable elements are mobile genetic units, DNA sequences that can detach from their region of origin and fit into another part of the genome. The sequences of these elements are very heterogeneous, as are their transposition mechanisms. They have a great importance in biology because of their high mutagenic power, their insertion in another occupied gene’s or regulatory’s region of the genome can lead to more or less serious modifications, important or silent mutations, and diseases.
Transposable elements also play an important role in evolution, just think that in organisms such as corn, 60% of the genome consists of sequences belonging to transposable elements, thanks to which they have selected favorable mutations over time, leading to the evolution of the species. Many transposable elements, in model organisms such as drosophila, zebrafish, mouse, rat and in humans, after mobilizing within the DNA, they have undergone further mutations so as to no longer allow their movement, and remain a fixed part of the genome. The study of transposable elements is playing an increasingly important role in research, in order to diagnose and treat diseases not yet fully understood.

15/05/2020

GMOs on food security 🧬🌱
Access to sufficient amounts of safe and nutritious food is key to sustaining life and promoting good health. Around the world almost 1 in 10 people fall ill after eating contaminated food each year, resulting in 420.000 deaths and the loss of 33 million healthy life years (DALYs). Food safety, nutrition and food security are closely linked. Unsafe food creates a vicious cycle of disease and malnutrition, particularly affecting infants, young children, elderly and the sick. In addition to contributing to food and nutrition security, a safe food supply also supports national economies, trade and tourism, stimulating sustainable development. The globalization of food trade, a growing world population, climate change and rapidly changing food systems have an impact on the safety of food. WHO aims to enhance at a global and country level the capacity to prevent, detect and respond to public health threats associated with unsafe food. One of the solutions to these problems seems to be the use of GM foods. Genetically modified (GM) foods are foods derived from organisms whose genetic material (DNA) has been modified in a way that does not occur naturally, e.g. through the introduction of a gene from a different organism. The technology is often called “modern biotechnology” or “gene technology”, sometimes also “recombinant DNA technology” or “genetic engineering”. Currently available GM foods stem mostly from plants, but in the future foods derived from GM microorganisms or GM animals are likely to be introduced on the market. Most existing genetically modified crops have been developed to improve yield through the introduction of resistance to plant diseases or of increased tolerance of herbicides. GM foods can also allow for reductions in food prices through improved yields and reliability.
In the future, genetic modification could be aimed at altering the nutrient content of food, reducing its allergenic potential or improving the efficiency of food production systems. However there are many discordant thoughts on the use of GMOs, and this technique requires deep studies to minimize the side effects both on food and on the ecosystems.

13/05/2020

Pharmacogenomics🧬💊 is the study of how genes affect a person’s response to drugs. This relatively new field combines pharmacology (the science of drugs) and genomics (the study of genes and their functions) to develop effective, safe medications and doses that will be tailored to a person’s genetic makeup.
Many drugs that are currently available are “one size fits all,” but they don't work the same way for everyone. It can be difficult to predict who will benefit from a medication, who will not respond at all, and who will experience negative side effects (called adverse drug reactions). Adverse drug reactions are a significant cause of hospitalizations and deaths in the United States. With the knowledge gained from the Human Genome Project, researchers are learning how inherited differences in genes affect the body’s response to medications. These genetic differences will be used to predict whether a medication will be effective for a particular person and to help prevent adverse drug reactions. Conditions that affect a person’s response to certain drugs include clopidogrel resistance, warfarin sensitivity, warfarin resistance, malignant hyperthermia, Stevens-Johnson syndrome/toxic epidermal necrolysis, and thiopurine S-methyltransferase deficiency.
The field of pharmacogenomics is still in its infancy. Its use is currently quite limited, but new approaches are under study in clinical trials. In the future, pharmacogenomics will allow the development of tailored drugs to treat a wide range of health problems, including cardiovascular disease, Alzheimer disease, cancer, HIV/AIDS, and asthma.
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All credits to:

08/05/2020

CRISPR/Cas9 🧬🛠

Targeted genome editing using engineered nucleases has rapidly gone from being a niche technology to a mainstream method used by many biological researchers. This widespread adoption has been largely fueled in 2012 by the emergence of the clustered, regularly interspaced, short palindromic repeat (CRISPR) technology, a genetic manipulation tool derived from the defense system of certain bacteria against viruses and plasmids.
CRISPR/Cas9 uses an important new approach for generating RNA-guided nucleases, such as Cas9, with customizable specificities. This method is easy to apply and has been used in a wide variety of experimental models, including cell lines, laboratory animals, plants, and even in human clinical trials. The CRISPR/Cas9 system consists of directing the Cas9 nuclease to create a site‑directed double‑strand DNA break using a small RNA molecule as a guide. A process that allows a permanent modification of the genomic target sequence can repair the damage caused to DNA. The simplicity and flexibility of the CRISPR/Cas9 site-specific nuclease system has led to its widespread use in many biological research areas including development of model cell lines, discovering mechanisms of disease, identifying disease targets, development of transgene animals and plants, and transcriptional modulation. Gene therapy has long-held promise to correct a variety of human diseases, this is the moment.
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All credits to: International Journal of Molecular Medicine and .research

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