TALEN genome editing to treat cardiovascular disease

Many factors give people a higher risk of cardiovascular disease, including high cholesterol, high blood pressure, smoking, obesity and inactivity. In recent years, genomic research has revealed some of the major genetic risks of cardiovascular disease. The 9p21.3 haplotype is the first common genomic region associated with an increased risk of coronary artery disease, a disease that destroys blood vessels that transport blood into the heart. It also increases the incidence of related diseases such as aneurysms and strokes. It is currently the most influential genetic cause of cardiovascular disease in the world. In the United States, it causes 10% to 15% of cardiovascular disease cases each year.

Although scientists know that the 9p21.3 haplotype is associated with an increased risk of disease, how this happens in the human body is still unknown. One challenge is that this disease risk haplotype is only found in humans and has a poor similarity to genomic regions in mice or other experimental animals. Another challenge is that this genomic region, called the 9p21.3 haplotype, lacks any protein-coding genes in the traditional sense, so it is difficult to predict what it might do.

To overcome these research challenges, in a new study, Professor Kristin Baldwin and his team at the Scripps Research Institute in the United States wanted to produce human vascular cells in culture dishes, which were then genetically studied using genome editing. They collected blood from people carrying a high-risk version of the 9p21.3 haplotype or a low-risk version, and allowed the cells in the blood to be reprogrammed to produce induced pluripotent stem cells (iPS cells). At this stage, the resulting iPS cells are genetically modified using a molecular scissors called transcription activator-like effector nuclease (TALEN) to remove 9p21 from affected donor cells and unaffected donor cells. Next, they induced these genetically edited iPS cells to become vascular smooth muscle cells and studied them in detail using high-resolution gene profiling and bioengineering methods. The results of the study were published online in the Cell Journal on December 6, 2018, under the heading “Unveiling the Role of the Most Impactful Cardiovascular Risk Locus through Haplotype Editing.”

The Baldwin team found that vascular smooth muscle cells derived from high-risk individuals exhibited extremely extensive abnormalities, and in these high-risk versions of 9p21.3 haplotypes, vascular smooth muscle cells (hereinafter referred to as high-risk vascular smooth muscle cells), more than 3,000 genes are affected — nearly 10% of the total number of human genes. Computer-based studies of these genes suggest that these high-risk vascular smooth muscle cells may be defective in critical functions associated with the disease. When tested in the laboratory, the Baldwin team found that mature high-risk vascular smooth muscle cells were more vulnerable than vascular smooth muscle cells carrying low-risk versions of 9p21.3 haplotypes (hereafter referred to as low-risk vascular smooth muscle cells). The contraction forces are smaller and less able to adhere to their surroundings.

Next, the Baldwin team wanted to know if the 3,000 or so genes might help uncover the effects of the recently discovered about 100 other genes associated with the risk of coronary artery disease. Unexpectedly, these high-risk vascular smooth muscle cells change over more than one-third of the genes (38 genes), suggesting that the 9p21.3 haplotype interacts with the gene network in some way or even control this genetic network.

Through more in-depth research, the Baldwin team identified a potential key major regulator (ANRIL), which is itself a member of a mysterious gene that does not produce proteins but produces long-chain non-coding RNA (lncRNA) molecules. They noted that high-risk vascular smooth muscle cells have higher levels of several shorter forms of ANRIL RNA. When they added these shorter ANRIL RNAs to healthy vascular smooth muscle cells, they developed key features of the disease, suggesting that these shorter ANRIL RNAs may be the master conductor of vascular smooth muscle cells converting between healthy and disease-promoting state. In addition, the use of genome editing to eliminate high-risk versions of the 9p21.3 haplotype in high-risk vascular smooth muscle cells would save their stability.

This study demonstrates the power of genome editing of pluripotent stem cells to study the genetic risks of human disease, especially where genetic risk is unique in the human genome region or in junk DNA. These findings not only provide new insights into how this high-risk version of the 9p21.3 haplotype disrupts vascular health, but also provide a new way to study and target gene regulatory networks that are widely involved in coronary artery disease.

It is worth noting that the 9p21.3 haplotype has such a significant effect on the functional and genetic characteristics of vascular smooth muscle cells. Although it does not encode a protein, its impact on the disease is significant. Given that this study reveals its role in destroying blood vessel walls, it is possible to develop a better way to stop it.

5 Ideas On How Your Dispensary Design Will Stand Out

Since the legalization of cannabis, dispensaries have emerged here and there. As the competition in the industry heats up, you need to find ways to make your dispensary stand out from the rest. The design of your store is one of the factors you should consider to stand out to those who search for “dispensary near me open.”

In a competitive industry such as cannabis, a sharp logo and nice website isn’t enough. If you find yourself competing with several dispensaries in your area, create a great dispensary design that will attract potential customers. Don’t know how to get started? Here are some tips for creating a design that stands out from the competition.

Open Floor Plan
As a dispensary owner, one of your topmost priorities should be the comfort of your customers. For first-time customers, visiting a cannabis can be an uneasy experience. Customers may find discomfort in your dispensary having cramped spaces. Implementing an open floor plan is one of the ways you can ensure a positive customer experience.

For example, you can put your inventory on the walls instead of cluttering the middle. You can align furniture symmetrically with the wall decorations and the lights. Keep in mind the importance of a clutter-free and balanced retail space.

Consider your ambiance
To attract more customers, you should also consider the ambiance of your dispensary as it relates with your branding. The atmosphere and character of your store should match your branding and target demographic. If your dispensary ambiance do not match your branding or audience. You run the risk of both turning away potential customers and harming your brand image.

Devise design elements that stimulates the sense of sight, sound, touch, and smell. Choose the kind of lighting and décor you will use, the kind of sound you want your customers to hear, and the texture or feeling of the surfaces.

Strategically use digital signage
Like most dispensary owners, you can easily get tempted to saturate your sales floor with digital signage and menus. You may also think of putting flat-screen TVs behind the counter and call it a day. Remember the customer’s journey should always be your priority.

Instead of behind the counter, why not position your flat-screen TVs next to display products so they will be educated about the product on display and feel less pressured to make a decision. Alternatively, you can use tablets to allow customers to review information about cannabis strains.

Reduce Wait Times
Cutting down on wait times is vital in a dispensary. You may have the most beautiful dispensary but if transactions take a long time, it won’t matter. At the same time, you don’t want to make customers feel they are being rushed out of the door. You need to strike a balance between excellent service and fast service.

Educate your customers
Some of your customers may be first-timers who may feel overwhelmed by all the choices laid to them on the table. You should make them feel comfortable by providing them with resources that will help them understand what they will be buying. Explaining to them the concepts and terminologies will make them feel at ease.

Men’s health: Top 6 Health Risks For Men.

Feeling Normal and productive is not a sign of a healthy body… most of the diseases are slowly progressing and with time their potency goes on increasing up until there are no more U-turns ahead. “Men put their health last. Their thinking is that if they can live up their roles in society, then they’re healthy” says Demetrius, editor in chief of American Journal Of men’s health. Men are also less likely to go to the doctor, only when their symptoms turn severe, they decide for medical help, but most of the time, it’s too late. Here are the top 5 health risks men need to be aware of

Cardiovascular problems

It was and still is a leading threat to men’s health. The reasons are not apparent but it is found that cardiovascular problems develop earlier in men than women. There are a variety of diseases in cardiovascular family e.g Heart arrest and hardened arteries being one of them and cardiac muscle hypertrophy being another, still, there could be so many complications in a man’s heart (pun intended) that can go unnoticed.

The popularity of cardiovascular disease in males is so widely known that a type of heart attack occurs because of blockage of a particular artery that supplies the heart itself is Called a widowmaker heart attack. Because of its potential to make widows once it’s blocked.

Men need to be aware of their Circulatory health, get cholesterol and BP checked frequently and immediately consult a doctor if they feel they are developing some symptoms that can not be explained based on a common cold or flu.

Prostate Cancer

One of the only diseases associated with men, because women do not seem to have prostates; a small gland behind the reproductive organ that secretes fluids necessary for Sperm health and nutrition and ejaculation.

This cancer, after skin cancer, is the most prevalent in men. WebMD reports say that while 1 out of every 6 men is diagnosed with it, only one out of 35 are likely to die from it.

Cancer, although slow-growing and not having a potency to spread to surrounding areas, is sometimes quite aggressive. And because there are no effective screening methods known yet, rectal examination (the gloved finger) remains on top followed by a Blood test for a prostate-specific antigen.

Specific causes for prostate cancer are not completely narrowed down yet, but there are some risk factors like age, race (black men are more vulnerable), obesity and Family history. Symptoms include trouble urinating and decreased force in Urine stream, Erectile dysfunction, blood in semen and bone pain.

Depression

Even though depression does not discriminate among genders, men are more likely to be less diagnosed with it because they try to act strong and responsible and do not convey normal symptoms of it like loneliness, crying, etc. putting on a fake mask of everything-is-okay and dying deep inside, all the while not seeking for help.

Research shows that depression is more prevalent in women but it’s riskier in men because they hide it- because society expects them to be strong. “So instead of showing sadness and crying, men get angry or aggressive” says Demetrius Porche, from the American journal of men’s health. “They feel it’s not okay for them to say ‘I’m depressed’ so they cope with it in wrong ways like drinking too much”

Depression can lead to one being suicidal and again, although women attempt more suicide, men are higher in the ratio of actually doing it. This only fact conveys a message of how strong depression can affect men. Hence if a man starts feeling emotional disturbances, they must seek help and not necessarily tell everyone that they are doing so.

Erectile dysfunction

Not life-threatening, it can be a threat to the continuation of a generation (to some extent under extreme conditions)

Erectile dysfunction is most of the time caused by Cardiovascular problems and stroke etc. and generally an erectile dysfunction means that the blood vessels in the body are not in a good mood to carry blood. Depression is also one of the causes of erectile dysfunction because one of its effects is the loss of interest in formerly pleasurable activities.

Proper treatment is less common than the temporary treatment methods of using blue pills and Cialis and all these temporary methods can cause major health problems like racing and irregular heartbeat, high blood pressure, irritability, extreme muscle aches, sudden hearing loss, vision impairment, and shortness of breath.

The dangers can be more severe if a person does not know about the contraindications of the drug they use for self-treating ED to have a more satisfying experience, which is the case in most men, sadly. Cialis contraindications, for instance, include, anaemia, low BP, angina, alcohol intoxication, bent penis with erection, ulcers, and seizures. If a person has any of these conditions; ED treating medications mustn’t be used

Alcohol use and unintentional injuries

The consumption of alcohol is more common amongst men than in women. Along with alcohol, smoking is also very common in men. Women do not smoke a lot.

Men have higher rates of alcohol-related deaths and hospitalization than women report Centre of disease control and prevention, and among drivers in fatal motor vehicle accidents, men are almost twice as likely as women to have been intoxicated.

Excessive consumption of alcohol can lead to aggression and inability to think and react properly hence causing hurting oneself or another. It seems that alcohol abuse and unintentional injuries, which can cause infections in men because their manliness does not allow them to respond to it properly, are closely related.

Increased alcohol use can also interfere with testicular function and hormone production, hence affecting the sexual health too, resulting in infertility, impotence, and reduction of male secondary sex hormone.

Forced by the society and their feelings of manliness, a male does have a hard time concentrating on his health and wellness and thinks that working for more hours and being more productive is what defines him when actually what defines him Is his attitude towards his life and life of others around him, who care for him. While being productive is an essential part of life, what good does productivity bring when it comes at the expense of one’s health.

Mesothelioma Causes – What Are the Symptoms Associated With Mesothelioma?

An individual that has been diagnosed with mesothelioma needs to take care of many different symptoms as well as inform you about the illness. In order to help those who are diagnosed with this type of cancer, there’s a mesothelioma wiki on the internet. That means you can also share your adventures with this disorder with others.

When you utilize the mesothelioma wiki, then you will be able to know exactly what you have to do to undergo the several symptoms. With a lot of folks dealing with exactly the same symptoms, they cannot always remember what it was like to handle them. It’s very good for those which aren’t in the know, but don’t want to learn everything about mesothelioma in the first location. It is possible to find out some facts and statistics about the disease and how much time it will take for you to feel its consequences.

This type of cancer is so devastating as it can cause some of the end-stage stages of different cancers. Some of the signs can differ from other cancers since the mesothelioma may not reveal as much of an affect. Many individuals don’t even have the right to live a full life just as they have been diagnosed with this deadly type of cancer. People that are diagnosed are not just allowed to die with the knowledge of having this disorder, but will have the right to live one with their loved ones. Those who have been diagnosed will find the chances to see and sense how it affects their lives.

When using the mesothelioma wiki, it’s vital that you be certain you don’t share your information. Just like the internet, if you didn’t create it yourself, then you shouldn’t use it. There are many people who have put their information on the internet, but they haven’t put much thought in their information that is being passed along.

A lot of people that suffer from this cancer will be aware of the usual symptoms that come together with the disease. The most common symptoms include loss of fat, muscle pain, and fatigue. These are all things that everyone has to address at some stage. Sometimes you might discover that the person has lost the capacity to walk or talk. But as there are a few essential things that is going to be happening as a result of the disease, you have to have a fantastic outlook on the procedure.

This specific cancer can be among the hardest forms of cancer to deal with. However, with time, they will find that they are losing their capacity to function in some way. It can become nearly impossible to leave the house or do some of those things that were once possible.

Employing the mesothelioma wiki is something which everybody should do at any point. With this understanding, you can help those out that suffer from this terrible disease. It is possible to find an idea on how much time you’ve left and what to expect. If you choose to share your information, you are giving somebody the chance to get more knowledge on this kind of cancer.

The indicators will get worse as the disease progresses. Among the most destructive things about mesothelioma is the fact that it is difficult to detect. By knowing all of the mesothelioma symptoms that are associated with this disorder, you will be in a much better position to take care of this.