Aspirin is a medicine you can buy at stores such as Wal-Mart, CVS, Walgreens, and even Dollar General. It's revered as one of the most effective and cheap drugs to bring down fever and a range of pain, not including the heartache of breaking up with your partner. Aspirin is the cause of a rare and near-fatal disease: Reye-Johnson, also called Reye's Syndrome, also called RS. September is Reyes awareness month, observed to spread awareness of this terrifying disease and remind parents not to give themselves or their children aspirin to relieve pain or fever while suffering from a viral infection. The exact mechanism or the cause of RS is unknown. However, a study showed a significant cause-effect relationship between aspirin intake and RS in children. A review reports that death happens in approximately 30%- 40% of cases. Children 5 to 14 years of age, recovering from viral infections such as influenza and chicken pox, are more susceptible to RS. However, there are reported cases of children less than one year, teens, and adults with RS. History of Reye's Syndrome Douglas Reye, an Australian pathologist, and colleagues first documented RS in 1963 as an encephalopathy with fatty degeneration associated with an 80% mortality rate. In his study, Reye described 21 children who presented with symptoms such as vomiting, rapid breathing, reduced blood sugar levels, and elevated liver enzymes. Seventeen out of the 21 children died within three days of disease progression. In 1965, suggestions that aspirin hypersensitivity could lead to RS were put forward by physicians. To date, the exact cause is still unknown.In the United States, RS surveillance commenced in the early 1970s leading to strict warnings against aspirin use in children.
The number of cases reported worldwide peaked between the 1970s and 1980s. In 1977, 454 cases of RS were reported in the United States. The increase in RS incidence rates correlated with a peak in influenza B and chicken pox viral epidemics. Approximately 555 cases of RS were documented in the U.S in 1980. In 1986 warnings were issued against aspirin, after which the number of cases fell from 0.63 per 100,000. The number of cases dropped to an average of 36 per year between 1987 and 1993. Features and Symptoms of Reye's Syndrome The symptoms of RS develop after recovery from a viral illness of the upper respiratory tract and, in some cases, gastroenteritis. There are five stages of clinical progression in RS. The first stage involves severe vomiting, lethargy, confusion, and drowsiness. Patients are in a nearly unconscious state or stupor during the second stage. Rapid breathing, lack of response to stimuli, and sluggish pupils are other common symptoms during the second stage. By the third stage, the patient's consciousness is more depressed, also called obtundation. The patient enters into a deep coma in the 4th stage, followed by death in RS's fifth and final stages. Mechanism of Reye's Syndrome As early as 1983, studies showed that the primary cause of RS is damage to liver mitochondrial structure and function. In RS, the liver shows reduced mitochondrial numbers. Liver biopsies show enlarged liver, high-fat content, and changes in mitochondrial structure. The high-fat content could be attributed to dysregulation of the breakdown of fatty acids and increased uptake of fatty acids by the liver. Similar observations were documented for brain biopsies, with swelling of the brain. The swelling in the brain leads to increased pressure in the skull or intracranial pressure that alters the amount of oxygen delivered to cerebral tissue. Biochemical characterization showed RS defects in the urea cycle, glucogenesis, and fatty acid oxidation pathways. The defective pathways could lead to the accumulation of high levels of neurotoxins such as ammonia and fatty acids leading to encephalopathy. High ammonia levels increase brain lactic acid production in RS, leading to brain swelling. Survivors with elevated ammonia levels usually have neurological deficits that last for the rest of their lives. These complications include poor attention span, memory loss, hearing, vision, and motor skills, and speaking difficulties. A study showed that aspirin increases mitochondrial fatty acid oxidation due to mitochondrial injury and defective respiration. Diagnosis and Treatment Although RS progress is rapid and fatal, there are a few ways to diagnose it. Diagnosis is not always specific, as other diseases show similar symptoms. Testing usually begins with the analysis of blood and urine and tests for fatty acid oxidation disorders and metabolic disorders. Invasive diagnostic tests include a spinal tap or lumbar puncture, liver biopsy, CT scan or MRI, and skin biopsy to test for fatty acid disorders. Current treatment focuses on managing symptoms such as administering glucose and electrolyte solutions, medications that lower intracranial pressure, and vitamin K to reduce bleeding from liver damage. Awareness Although the number of cases has significantly reduced since 1963, educating parents and caregivers about the detrimental effects of aspirin use and RS is essential. In 1974, the National Reyes Syndrome Foundation was established to eliminate RS cases worldwide by spreading awareness. The foundation supports research and serves families and individuals dealing with RS. They advocate for the safe use of aspirin in schools and raise awareness through health fairs, newsletters, and student projects. 9/28/2022 The Big Effects of a Small Bite!
Would you go to the doctor if an animal bit you? Probably not. How would your opinion change if you knew that rabies causes encephalitis, or swelling of the brain, and almost always results in death once symptoms are present? Today is World Rabies Day, an observance day that aims to raise awareness and promote the elimination of rabies on a global scale. Coordinated by the Global Alliance for Rabies Control (GARC), the theme for 2022 is "One Health, Zero Deaths." World Rabies Day is observed on September 28th of every year to commemorate the death of Louis Pasteur. Pasteur developed the first effective vaccine against rabies in humans in 1885. The Centers for Disease Control and Prevention and the GARC aim to eliminate dog-mediated human rabies by 2030. More About Rabies and Symptoms Rabies is a zoonotic disease caused by the Rabies Virus, also known as RABV, a negative-stranded RNA virus. It belongs to the genus Lyssavirus and is a member of the Rhabdoviridae family because of the virion's bullet shape. Rabies can cause around 60,000 human deaths every year around the globe. In the United States, bats, raccoons, and foxes carry the RABV. However, dogs are the primary carriers globally, with dog bites causing causing the overwhelming majority of human rabies infections and deaths. According to Dr. Amy Gilbert, a research biologist at the USDA and team leader for applied research to assist wildlife rabies management, "death is by lethal and progressive encephalitis, and one of the hallmarks of rabies is acute progressive deterioration." Both humans and animals rapidly deteriorate once symptoms begin to show. Dr. Gilbert noted that other zoonotic viruses also cause encephalitis. However, a unique to rabies is that "the reservoir host is susceptible to fatal infection", and “there are no asymptomatic wildlife carriers”, which is not present in many other zoonotic diseases.” The Centers for Disease Control reports that symptoms may not appear for weeks or even months once exposed to rabies. Common symptoms appear flu-like at first until developing into cerebral dysfunction, anxiety, agitation, and more. People can also experience delirium, hydrophobia, and insomnia, but the disease is typically fatal once these signs occur. Although rabies has a more extended incubation period, there have been less than 20 cases of human survival after the appearance of clinical rabies symptoms, so people must act quickly after a possible exposure has occurred. Schematic diagram of bullet shape structure of RABV showing different proteins. Liu, X., Nawaz, Z., Guo, C., Ali, S., Naeem, M. A., Jamil, T., Ahmad, W., Siddiq, M. U., Ahmed, S., Asif Idrees, M., & Ahmad, A. (2022). Rabies Virus Exploits Cytoskeleton Network to Cause Early Disease Progression and Cellular Dysfunction. Frontiers in veterinary science, 9, 889873. https://doi.org/10.3389/fvets.2022.889873 Fun Fact:Hawaii is the only state in the United States that is rabies free! What Causes Rabies in Humans? RABV enters the body through a bite or scratch from an infected animal. This wound exposes a person's muscle tissue to the infected animal's saliva, which contains RABV particles. The location of the wound, typically in muscle tissue, allows the virus to spread. In 1996, a study showed that the muscular form of the nicotinic acetylcholine receptor (nAChR) binds RABV allowing it to enter the muscle cell. A review of the rabies neuroinvasion mechanism suggests that RABV buds off muscle cells followed by entry into the central nervous system. The access occurs via neuromuscular junctions, specialized synapses between nerve terminals and muscle fibers. The RABV entry into nerve cells follows viral replication and a new round of infection and spread. There are a few instances of rabies transmission through corneal or solid organ transplants, but but most virus transmission occurs through bites or scratches from rabid animals. The Biology of RABV A recent review shows that RABV comprises complex genomic RNA and nucleoproteins within a lipid envelope. It is the most prominent of the 17 species of lyssaviruses. RABV structure resembles a bullet. Studies show that rhabdoviruses encode five different structural proteins: nucleoprotein (N), phosphoprotein (P), matrix protein (M), glycoprotein (G), and an RNA-directed RNA polymerase (L). The N protein protects the RABV genome from RNAse and is the major component of the nucleocapsid. It encapsulates the RNA to form a ribonucleoprotein complex or RNP. The RNP then interacts with P and L proteins to form the nucleocapsid. The P protein function in the replication and transcription allows the RABV to invade the host interferon-mediated antiviral response. It is also the non-catalytic part of the L polymerase protein. The M protein links the nucleocapsid to the viral envelope. The M protein also aids in budding, apoptosis, and intercellular membrane redistribution of the virus. The virus G protein must attach to cellular receptors and enter the cell via endocytosis to establish infection. Once inside the cell, the virus uncoats and releases its helical nucleocapsid into the host cell's cytosol. RABV is a negative sense RNA virus. The viral polymerase transcribes the negative strand to five positive-strand monocistronic mRNAs before protein synthesis. More information on RABV structure and replication is reviewed here. A way to identify RABV on a cellular level is the presence of Negri bodies. Negri bodies are composed of RABV proteins and RNA Rabies Vaccination Rabies vaccination is unique because it can be administered pre- and post-exposure in humans. Pre-exposure vaccination is available for those traveling to RABV-endemic regions or people at enhanced risk of coming in contact with RABV, such as spelunkers, researchers, veterinarians, and individuals who handle wild animals. Post-exposure vaccination is available because possible exposure, via bite or scratch, is easily identifiable. The virus' incubation period is long enough to allow the vaccine to develop a protective immune response within the recipient. Both types of vaccinations involve multiple vaccine doses administered according to a regimen, or schedule, but there are different post-exposure recommendations for persons who have or have not had pre-exposure vaccination, or persons who may have immunocompromising conditions. Dr. Gilbert discussed differences in the vaccines given to humans and wildlife. Wildlife vaccines are "oral, and a primary difference is that the vaccines for wildlife are live, not inactive." She added, "the products used for animals in the United States are live but can never cause rabies because they are recombinant." A recombinant vaccine is a vaccine produced by genetically modifying the viral genome. Dr. Gilbert said, " In animals, vaccines are given before to prevent infection. There is no benefit to vaccinating them once they are infected and showing signs and symptoms." If 70% or more of the dog population gets vaccinated, the rabies infection rate will rapidly decrease, reducing the human infection rates and exposure drastically. Dog vaccination is a critical element of rabies control for human and animal populations, but these vaccinations must be appropriately tracked, registered, documented, and followed up. Rabies Is a Neglected Disease It is very likely that every person reading this article has heard of rabies and has some understanding of its transmission from animals, but rabies is a neglected tropical disease. Compared to other zoonotic diseases, rabies is neglected, despite its significance and impact. The condition is endemic in locations on almost every continent. While many countries are now canine rabies-free, the disease is prevalent in bat populations in most countries in the Americas and other lyssaviruses are found in bat populations throughout the Old World. One reason why rabies might still be a neglected zoonotic disease in developing countries is the lack of laboratory diagnosis and surveillance for both human and animal rabies in developing countries where the disease is endemic. Due to the lack of simple and cost-effective laboratory methods for diagnosis, rabies' burden and public health impact are uncertain and likely underestimated. Even though rabies is almost always fatal once symptoms become apparent, there is a low commitment to controlling rabies due to various factors. Dr. Gilbert said, "rabies is a neglected disease because it primarily impacts the poorest and most under served communities." She added, "a cycle of neglect is created in these locations with limited reporting, which leads to low prioritization of the problem, and this cycle continues." This neglect has led to "advocacy efforts to start pre-exposure campaigns in communities heavily impacted by rabies." There is no effective therapy for rabies once clinical symptoms set in. How to Spread Awareness In the United States, people do not commonly talk about rabies or its effects on many developing countries. Although many people do not believe rabies concerns them, the One Health concept highlights the dynamic between the health of animals, the environment, and humans. In this respect, people should consider the health of those around them and those worldwide who suffer from diseases that more advanced countries no longer worry anymore. Dr. Gilbert believes World Rabies Day should be used to "raise awareness on rabies facts, and get people to remember that rabies is still around even though there are few human deaths in the US." She added, "we know that many people are exposed and receive post-exposure treatment each year." The first step in changing people's minds about rabies is simply getting people to walk into a doctor's office after a possible exposure. People can call their local health department if they are concerned about a possible RABV infection because they will have information on potential concerns about rabies spread in a particular area. One Health Vaccinations benefit wildlife, domestic animals, and public health. Dr. Gilbert said, "rabies is one of the best examples of One Health we have." She also noted that, "each case of rabies on averages leads to one or two additional cases, but explosive outbreaks are uncommon." One Health approaches focus on controlling rabies at its source in animals, for the benefit of public health, agriculture, and natural resources. This approach will help lower the economic costs of living with rabies. The One Health system benefits developing countries by creating a more economical rabies prevention and control method compared to approaches that focus only on reactive post-exposure prophylaxis. One Health approach has been successful in Bhutan, Bangladesh, and Sri Lanka and is currently used in Nepal. Bangladesh lowered their rabies deaths by 1300 within three years, and Sri Lanka reduced their rabies-related deaths to less than 50 in a year. As the prevalence of rabies control programs grows, countries can look to these programs that use a One Health approach to design effective animal rabies control programs in their own country. With One Health in mind, many countries will be able to eliminate rabies within their communities while supporting the coexistence of humans, domestic animals and wildlife.” 9/27/2022 Too Late Too Often!
By Lucy Hallmark
Freshman, Biochemistry Major Mississippi State University
Polycystic ovary syndrome (PCOS) is an endocrine disorder that affects 6â12% of women of reproductive age globally. Hormonal imbalance and ovarian dysfunction are two significant hallmarks of PCOS.
A recent study shows that women with PCOS are at a higher risk of developing infertility, cardiovascular diseases, diabetes, hypertension, and obesity. The lack of guidelines for accurate clinical identification and knowledge gaps among providers pose a challenge for PCOS diagnosis. Most women discover they have PCOS after experiencing infertility issues. September is PCOS Awareness month. Throughout this month, PCOS Challenge: The National Polycystic Ovary Syndrome Association sponsors and organizes events and provides resources and information regarding PCOS. A little history Polycystic ovary syndrome was initially described in 1721 by Italian physician Antonio Vallisneri. He reported the case of a peasant woman who was obese, infertile, and had enlarged ovaries, which were described as white and shiny. It wasnât until 1935, when Dr. Irving Stein and Dr. Michael Leventhal published a report entitled âAmenorrhea associated with polycystic ovaries,â that any progress in diagnosing the disease began. Leventhal and Stein defined three criteria that remain to this day vital in the diagnosis of PCOS. Theirs was the first report of patients suffering from polycystic ovaries and PCOS-related symptoms. They also were one of the first researchers to suggest that the abnormalities resulted from a hormonal imbalance. What are the symptoms of PCOS? Women affected by PCOS miss or have delayed irregular periods. Per Rotterdam criteria, PCOS has three key features: Anovulation, hyperandrogenism, and polycystic ovaries. You must display at least 2 of these criteria to be diagnosed with PCOS. Anovulation happens in women of childbearing age when an egg is not released during the menstrual cycle. The primary cause is excessive androgen production, also called functional ovarian hyperandrogenism leading to small pre-ovulatory follicles that fail to respond to normal concentrations of follicle-stimulating hormone. Small ovarian follicles preferentially metabolize androgens to make male hormones like testosterone. This is due to high levels of the enzyme steroid 5α-reductase found in small ovarian follicles that process hormones for male sexual development. In women of childbearing age, PCOS is detected in the late teens or early 20s when symptoms like excessive coarse hair growth on the face, chest, and back, acne, and irregular periods surface. Excessive hair growth is referred to as hirsutism. What are the causes of PCOS? Four schools of thought provide a hypothesis for the pathogenesis of PCOS. They are the top-down, bottom-up, androgen theory, and insulin schools of thought. The top-down school hypothesizes that PCOS results from the aberrant production of the luteinizing hormone, LH, which translates into inadequate follicular maturation. Increases in serum LH levels lead to enlargement of the ovarian theca cells, which causes the overproduction of ovarian androgens. The bottom-up school suggests that the root cause is the conversion of adrenal androgens such as D4 androstenedione or D4A into estrone or E1 in the peripheral adipose tissues. E1 sensitizes the pituitary gland resulting in the overproduction of LH. Excessive LH stimulates the thecal cells causing the overproduction of androgens. The school of androgen theory emphasizes that ovarian hyperandrogenism is the primary cause of PCOS. The insulin school links high androgen levels with hyperinsulinemia or overproduction of insulin. Excessive insulin accompanied by insulin resistance is a significant factor predisposing women to PCOS. High insulin levels reduce androgen clearance and enhance steroidogenesis in the adrenal glands and ovarian theca. Endocrine mechanisms that control PCOS are reviewed in detail here. PhysioPathoPharmaco 2020 [YouTube Channel] Polycystic Ovarian Syndrome (PCOS) - Pathophysiology, Symptoms, Treatment By Bryce Miller Sophomore, Biochemistry Major Mississippi State University
In humans, the ATXN1 gene codes for the protein ataxin-1, whose function is not fully known.
The SCA1 is a repeat expansion disease, meaning a part of the DNA made up of building blocks cytosine, adenine, and guanine, referred to as CAG nucleotide repeat, occurs multiple times in the ATXN 1 gene. The CAG trinucleotide repeat on the ATXN 1 gene triggers the SCA1 disorder. The codon CAG codes for the amino acid glutamine abbreviated Q. Therefore, SCA1 is also called a polyglutamine or poly Q disorder. In SCA1, ATXN1 alleles can carry 39–81 CAG repeats. The CAG trinucleotide in ATXN 1 gene results in excessive glutamine in the ataxin-1 protein. The extra glutamine increases the length of the protein, which causes it to misfold. The misfolded ataxin-1 protein forms clumps or aggregates with other proteins preventing ataxin-1 from performing its normal function and cell death. The cells in the cerebellum, the part of the brain that coordinates movement, are susceptible to changes in ataxin-1 function leading to SCA1. What are the Symptoms and Signs of SCA1? The symptoms of SCA 1 develop in the mid-thirties and rarely in early childhood or late in life. Patients start showing problems with walking and coordinating hand movements. Unsteady gait, limping, and poor coordination in various body parts are common during the disease's initial stages. Patients have trouble expressing their thoughts due to slurred speech. Patients with SCA1 can have dysphagia, or difficulty swallowing, increasing the risk of choking while eating and drinking. Eye movement can also be affected, causing eyes not to focus or move to their desired location quickly. All of these symptoms result from the degeneration of the cerebellum. How is SCA1 Diagnosed? Current diagnostic methods employ blood tests, imaging studies through MRI, lumbar puncture or spinal tap, and molecular genetic testing. Molecular genetic testing can identify SCA1 cases accurately. Patients who have ATXN 1 alleles with 39 or more CAG trinucleotide repeats are 100% affected by SCA1 . An MRI of the brain can show cerebellar shrinkage in patients with ataxia. Treatment and Management There is no treatment for SCA1 yet. As SCA1 is a monogenic disease, current strategies target the ATXN1 gene. A study using conditional transgenic mouse model of SCA1 showed that preventing mutant ATXN1 expression during the initial phase of the disease results in improved coordination and motor activities. Another study in SCA 1 mice showed that RNA Interference by shRNAs and siRNAs targeting mutant ATXN1 led to a reduction in the ATXN1 inclusions, restored cerebellar morphology, and improved motor function. Antisense oligonucleotides targeting ATXN1 RNA expression has shown promising results in mouse models of SCA1. 9/24/2022 The Cancer of the Butterfly Gland!
Wait! No Signs or Symptoms? That's right! Almost no signs or symptoms are present during the early stages of thyroid cancer development. In most cases, a painless lump, known as a nodule, will develop around the neck area. If the disease progresses to its advanced stages, some patients may experience swelling of the neck, voice changes, and difficulty swallowing. If you are starting to worry, don't! Tiny thyroid nodules exist undetected in one in every three adults. Most nodules located on the thyroid are benign, meaning noncancerous. The American Thyroid Association does not recommend the biopsy of nodules less than 1 cm. Nodules less than 1 cm are benign, but if you notice a lump or swelling on your neck, it is always best to check with your doctor. When the diameter exceeds 1 cm, this may indicate something serious. Early detection is critical, so advocating for more routine thyroid examinations is essential. What Do We Know About the Molecular Mechanism of Thyroid Cancer? Thyroid cancer is a common malignancy of the endocrine system. Hence, players in the signaling pathways that respond to changes in thyroid levels are altered in thyroid cancer. The alterations include genetic changes such as mutations, copy number variation, and epigenetic changes such as aberrant DNA methylation. What is Thyroid, and What Does it Do? The thyroid is a butterfly-shaped gland in front of our necks, directly below the voice box. Its primary purpose is to regulate our body's metabolism. In humans, the thyroid hormone is crucial to regulate the body's metabolism, development, growth, and neural differentiation. The Thyroid produces three main hormones: triiodothyronine (T3), thyroxine (T4), and calcitonin. These hormones instruct your cells on how much energy to use. Iodine from the diet is a critical building block of T3 and T4 hormones. More specifically, T3 and T4 regulate your metabolism and body temperature, whereas calcitonin is responsible for maintaining calcium levels in your blood and bone health. Calcitonin opposes the function of the parathyroid hormone, which increases blood calcium levels. When there is an imbalance of thyroid hormones, side effects such as weight gain or weight loss and an overall loss of energy are common. The "MVP"- The Pituitary Gland The pituitary gland is located at the base of the brain and is responsible for producing a hormone called TSH, or the Thyroid Stimulating Hormone. The TSH triggers the thyroid cells to make the thyroid hormones: T3 and T4. When levels of thyroxine and triiodothyronine are elevated, the pituitary gland does not produce TSH. When T4 and T3 levels drop, the pituitary gland makes more TSH. My Story: An Insight into the Beginning Stages of Thyroid Cancer Development Thyroid nodules develop in approximately 5%- 7% of individuals during physical examination. You might think, "This will never happen to me, right?" Until middle school, I had the same thought process, until one day, during a routine doctor's visit, I heard the words, "Have you ever noticed this lump on your neck?" I thought to myself, "Lump on my neck? That can't be possible; I would definitely notice something like that." But I was wrong. I didn't notice any lump on my neck, though it was already grown past the size of being suspicious, almost 1 inch in diameter. That day, I scheduled an appointment with Le Bonheur's Children's Hospital to get a biopsy on the thyroid lump. During this procedure, a small tissue sample was collected from the nodule and sent to a laboratory to test for cancerous activity. When the results returned as benign, I felt like a great weight lifted off my shoulders. Although harmless, I was informed the likelihood of it developing into cancer is high. At that moment, I had two options: have the nodule biopsied every six months to monitor its development or undergo a partial thyroidectomy to remove the nodule and half my thyroid gland. After thoroughly thinking about the pros and cons of each, I decided I wanted to minimize my risk of developing cancer in the future, so I decided to undergo surgery to have half my thyroid removed. In some cases, partial thyroid removal will still incite normal thyroid function. However, I was diagnosed with hypothyroidism, an underactive thyroid, after my surgery. I was prescribed levothyroxine, a medicine to replace the missing thyroid hormone thyroxine. To this day, I am very thankful to my primary provider and the staff at Le Bonheur's Children's Hospital for helping me through one of the scariest times in my life. What are the Types of Thyroid Cancer? There are two main subtypes of thyroid cancer: differentiated and undifferentiated. Differentiated thyroid cancers originate from follicular cells responsible for producing thyroid hormones. These cancer cells resemble healthy thyroid cells and respond well to treatment. The two common types in this category are Papillary Thyroid Cancer, making up to 80% of thyroid cancer, and Follicular Thyroid Cancer, which constitutes 10-15%. Non-differentiated thyroid cancer originates from cells that control calcium levels. These cancer cells do not look like healthy thyroid cells and do not respond well to treatment. With a lower frequency of occurrence, Medullary Thyroid Cancer, Anaplastic Thyroid Cancer, and Thyroid Lymphoma are the three common types of non-differentiated cancer. What Do We Know About the Molecular Mechanism of Thyroid Cancer? Thyroid cancer is a common malignancy of the endocrine system. Hence, players in the signaling pathways that respond to changes in thyroid levels are altered in thyroid cancer. The alterations include genetic changes such as mutations, copy number variation, and epigenetic changes such as aberrant DNA methylation. Several gene mutations lead to various types of thyroid cancer. Mutations in the BRAF gene, coding for the BRAF V600E protein, constitute 45% of papillary thyroid cancer cases. Mutations in the RET/PTC oncogene exist in 10-20% of papillary thyroid cancer cases. The second most common mutation in thyroid cancer is in the RAS protein. The RAS mutations preferentially activate the PI3K–AKT signaling pathway in thyroid tumorigenesis. A comprehensive review of all gene alterations contributing to thyroid cancers can be found here. Why Should You Care? This year, over 45,000 people in the United States will be diagnosed with thyroid cancer. Of those 45,000 individuals, approximately 2,000 will lose their life to the disease. Worldwide, thyroid cancer affects over half a million individuals, with 50,000 dying due to the condition. Knowing more about the disease will help improve our treatment options and patient care quality. If that isn't reason enough, thyroid cancer research can help us to understand more about how cancer works in general, and the findings may transfer to treatment for other cancers. Thyroid cancer awareness is recognized one month out of the year, but after reading this article, I hope you educate people about thyroid cancer every time you get the chance 9/21/2022 0 Comments Forget Me Not!
By Sophie Maedo
Junior, Biochemistry major Mississippi State University
Nature Videos 2017 [YouTube Channel] Inside Alzheimer's Brain
The Tau Protein and Neurofibrillary Tangles The Tau, a microtubule-associated protein, is the primary component of NFTs. The Tau protein function to provide stability to microtubules of mature neurons. Tau contains post-translationally modified phosphate groups in its microtubule assembly domain in healthy neurons. In Alzheimer's, a hyperphosphorylated form of Tau accumulates in neurons, resulting in the breakdown of the neural cytoskeleton. A study shows that Tau's phosphorylation at residues outside the microtubule-binding domain detaches Tau from the microtubules resulting in the formation of aggregates. The tau aggregates then accumulate to create the twisted helical filaments known as NFTs. A New Alzheimer's Mechanism For the past thirty years, scientists have mainly conducted research under the amyloid cascade hypothesis. However, a recent study linked impaired autophagy to Alzheimer's disease and proposed that lysosomal dysfunction leads to the formation of amyloid plaques. During autophagy, a section of a neuron's cell membrane elongates to engulf cytoplasm or specific cellular material that needs to be broken down, resulting in the formation of an autophagosome. The autophagosome fuses with a lysosome to form an autolysosome. The lysosomal membrane has vATPase, a proton pump that helps acidify the lysosome. The acidic environment activates hydrolase, which is an enzyme that catalyzes the breakdown of molecules with the use of water. When vATPase function is compromised, it causes the deacidification of lysosomes leading to neurodegenerative diseases. During the autophagy lysosomal pathway, the autolysosome engulfs APPs, breaking these proteins into smaller Aꞵ peptides. The autolysosome can clear these Aꞵ peptides in a healthy cell. However, in cells plagued by Alzheimer's disease, the autolysosome function is compromised, and the concentration of Aꞵ increases. The study also shows that the autolysosome in cells with Alzheimer's disease experienced deficiencies with vATPase early in the disease progression. This results in poor acidification of lysosomes and elevated levels of Aꞵ. An important distinction was that the lysosomal dysfunction occurred before any accumulation of amyloid plaque formation. The observation suggests that amyloid plaque formation could result from faulty lysosomes. While several therapeutic trials and strategies based on the amyloid hypothesis have failed, the new mechanism may provide direction to develop novel treatments that target the dysfunction in the autophagy lysosomal pathway. |
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