mechanisms of disease

For the smols (tag yourself)

Cutie Smol
-wears oversized sweaters
-is soft and huggable
-sits in everyone’s lap
-has everyone eating out of the palm of their hand

Angry Smol
-sick of the tols and their shit
-is determinedly the big spoon
-curb stomper boots and leather jackets with an attitude to match
-will fight you to prove a point

Bouncy Smol
-too much energy for one small package
-loud and proud
-climbs EVERYTHING, even people, especially people
-will never go unnoticed even though they are below everyone’s sight range

Apathetic Smol
-just wants to sleep forever
-will let all of the friends lean on their head but ONLY the friends
-will quite willingly use their height to disappear if everything is too much
-sarcasm is a coping mechanism for that disease called humanity

y’all i’m so overwhelmed by how much art mine and charbons’ butterfly disease au has gotten??? i can’t even believe it omg so here is a little primer on what the au is actually about/how the disease works:

the disease is similar in mechanics to hanahaki disease (where the afflicted starts to grow flowers in their lungs/stomach due to unrequited love), only the opposite. the butterfly/papillon disease develops when someone feels extreme guilt for breaking another person’s heart. this doesn’t necessarily mean that the afflicted does not return the feelings, but rather that they won’t allow themselves to return the feelings.

Keep reading

Discovery of Neurotransmission Gene May Pave Way for Early Detection of Alzheimer's Disease

A new Tel Aviv University study identified a gene coding for a protein that turns off neurotransmission signaling, which contributes to Alzheimer’s disease (AD).

The gene, called RGS2 (Regulator of Protein Signaling 2), has never before been implicated in AD. The researchers report that lower RGS2 expression in AD patient cells increases their sensitivity to toxic effects of amyloid-β. The study, published in Translational Psychiatry, may lead to new avenues for diagnosing Alzheimer’s disease — possibly a blood test — and new therapies to halt the progression of the disease.

The research was led by Dr. David Gurwitz of the Department of Human Molecular Genetics and Biochemistry at TAU’s Sackler School of Medicine and Prof. Illana Gozes, the incumbent of the Lily and Avraham Gildor Chair for the Investigation of Growth Factors; Head of the Elton Laboratory for Molecular Neuroendocrinology at TAU’s Sackler School of Medicine; and a member of TAU’s Adams Super Center for Brain Studies and TAU’s Sagol School of Neuroscience. Also participating in the research were their PhD student Adva Hadar and postgraduate student Dr. Elena Milanesi, in collaboration with Dr. Noam Shomron of the Department of Cell and Developmental Biology at TAU’s Sackler Faculty of Medicine and his postgraduate student Dr. Daphna Weissglas; and research teams from Italy and the Czech Republic.

Identifying the suspect

“Alzheimer’s researchers have until now zeroed in on two specific pathological hallmarks of the chronic neurodegenerative disease: deposits of misfolded amyloid-β (Aβ) peptide plaques, and phosphorylated tau protein neurofibrillary tangles found in diseased brains,” Dr. Gurwitz said. “But recent studies suggest amyloid-β plaques are also a common feature of healthy older brains. This raises questions about the central role of Aβ peptides in Alzheimer’s disease pathology.”

The researchers pinpointed a common suspect — the RGS2 gene — by combining genome-wide gene expression profiling of Alzheimer’s disease blood-derived cell lines with data-mining of previously published gene expression datasets. They found a reduced expression of RGS2 in Alzheimer’s disease blood-derived cell lines, then validated the observation by examining datasets derived from blood samples and post-mortem brain tissue samples from Alzheimer’s patients.

“Several genes and their protein products are already known to be implicated in Alzheimer’s disease pathology, but RGS2 has never been studied in this context,” Dr. Gurwitz said. “We now propose that whether or not Aβ is a primary culprit in Alzheimer’s disease, neuroprotective mechanisms activated during early disease phases lead to reduced RGS2 expression.”

Sensitizing brain neurons to potential damage

The new TAU study furthermore proposes that reduced RGS2 expression increases the susceptibility of brain neurons to the potentially damaging effects of Aβ.

“We found that reduced expression of RGS2 is already noticeable in blood cells during mild cognitive impairment, the earliest phase of Alzheimer’s,” Dr. Gurwitz observed. “This supported our theory that the reduced RGS2 expression represents a ‘protective mechanism’ triggered by ongoing brain neurodegeneration.”

The team further found that the reduced expression of RGS2 was correlated with increased Aβ neurotoxicity. It acted like a double-edged sword, allowing the diseased brain to function with fewer neurons, while increasing damage to it by accumulating misfolded Aβ.

“Our new observations must now be corroborated by other research groups,” Dr. Gurwitz concluded. “The next step will be to design early blood diagnostics and novel therapeutics to offset the negative effects of reduced expression of the RGS2 protein in the brain.”

Human Central Nervous System and Peripheral Nervous System Connections

The central nervous system (CNS) of the human consists of the brain, spinal cord, and cranial nerve II (the optic nerve which connects to the eyeball).

When compared to the peripheral nervous system (PNS), the CNS differs in several key ways. It’s largely autonomic (requires no input for it to work) instead of voluntary, is much more protected (by bone and the blood-brain barrier), and interprets input, rather than integrating it.

As the PNS is much less protected, it’s vulnerable to damage by toxins, disease, mechanical injury, and autoimmune disorders. The degenerative conditions of the CNS are almost always hereditary.

Dictionnaire Universel d'Histoire Naturelle. Charles d'Orbigny, 1849.

Types of Pathogenic Microorganisms


The average human body contains about 10 trillion cells. Imagine how much that is! If our population was 1400 times greater in the entire world, then we still would not be more than the number of cells in the entire body. Amazing isn’t it? 

But what if I tell you the gut alone, contains 100 trillion microorganisms living within it this very minute? And hence the picture above, our world is really a microorganism’s world, we are simply the ones large enough to be seen. 

And thus we see the importance of microbiology, how exactly are these microorganisms affecting our lives? 

Most of these microorganisms are actually beneficial to our body, for example, by aiding in the process of digestion, however, there are microorganisms that are damaging to their host, either by the production of toxic products, or direct infection, and these microorganisms are termed pathogenic. 

To have an idea of this, let us talk about the types of microorganisms, and the pathogenic ones in each type, that is, the one that can give us a disease. 

Microbes that Cause Diseases

Microbes that cause diseases can be divided into 5 groups of organisms:

  1. Bacteria
  2. Fungi
  3. Protozoa
  4. Helminths and Rotifiers
  5. Viruses

There is also a recently discovered type of microbe that can cause a disease, known as a prion. 

Of these microbes, we can classify them in several different ways. 

Classification of Microbes:

Firstly, it is important to consider the status of prions and viruses. Technically, these “microbes” are not living. Prions are simply misfolded proteins, and viruses are only “alive” when they infect an organism. Thus, both prions and viruses have their own classifications. 

As for the other organisms, we can classify them in several ways:

  • Eukaryote vs Prokaryote
    • In this classification scheme, all bacteria are prokaryotes, and fungi, protozoa, helminths and rotifers are eukaryotes. 
      • The prokaryotes are further subdivided into eubacteria and archaebacteria. Eubacteria are the medically important bacteria, while archaebacteria are a group of evolutionarily distinct bacteria. 

Differences between Eukaryotes and Prokaryotes:

  • General Size
    • Eukaryotes are much larger than Prokaryotes, being about 10-100mm in diameter. 
    • Prokaryotes are much smaller, being about only 0.2-2mm in diameter. 
  • Nucleus vs Nucleoid: 
    • Eukaryotic cells contain a true nucleus, with multiple chromosomes, linear DNA, and a nuclear membrane, using mitotic apparatus to ensure chromosomes are equally distributed to the daughter cells. 
    • Prokaryotic cells contain a nucleoid, which is an area of loosely organized, circular supercondensed DNA, lacking nuclear membrane and mitotic apparatus.

Keep reading

Coping tips - What I do when I'm feeling down.

With a chronic illness sometimes it’s a big challenge to stay positive and put yourself up when you’re really down.
In the last couple of years I found out what helps me coping with this down-periods of my illness!

Here are my personal ten tips:

1. Take your iPod/mp3-player, turn on your favourite music and dance through your room until you feel free! Dancing alone in your dark room is one of the best things to get all the bad thoughts out of your head.
(Even if you’re weak and tired it helps to do a bit of in-bed-dancing.)

2. Go outside for a short walk. See and feel the beauty of the nature.

3. Eat chocolate or whatever your favourite food is. (If you have any appetite)

4. Read a good non-illness related book.

5. Phone one of your friends/family members, talk to them about your problem or try to make fun to clear your mind!

6. Write down your thoughts or the part of your story you think you have a problem with. Sometimes it can be helpful to write down the whole story to understand who you are and where your problems come from.

7. Paint a picture to express your feelings.

8. Talk to other people with similar problems. BUT please choose people that don’t bring you down even more!

9. Work and try to be productive to get more self-esteem and to tell yourself that you’re so much more than your illness.

10. Go for a walk with a dog or cuddle with a cat. A. Cute animal always helps to cheer up.

What are your favourite tips for staying positive? Any other coping strategies?

2

VIDEO: Biophotonics is poised to make major breakthroughs in medicine! At the Center for Biophotonic Sensors and Systems at Boston University, engineers and scientists are collaborating with industry to realize the potential of light waves in the diagnosis and treatment of disease, and much more. Watch the research in action in this video: https://www.youtube.com/watch?v=7OR1tiDIK_g

A Transformational Leap Toward Precision Medicine

It wouldn’t be crazy to believe a new era in health and longevity is starting based on research coming out nearly every week, which highlights the power of bringing big data analytics, genetics, clinical testing and biotechnology together. 

Scientists recently revealed that applying computer science to more than 15,000 electronic medical records had revealed a way to predict more than a day in advance when a patient was likely to suffer potentially deadly septic shock. Others have used massive amounts of data from an entire country’s population to uncover the connections between the appearance of seemingly unrelated traits with later disease development. Examples abound.

Now biomedical researchers at the University of California, San Francisco say your gut reaction to the expanding volume of discovery isn’t wrong–the world is indeed on the cusp of a healthcare revolution. That revolution will occur thanks to precision medicine, a computer-driven approach to organizing and synthesizing all the available biomedical information. Learn more and see an infographic below.

Keep reading

Scientists Uncover Common Cell Signaling Pathway Awry in Some Types of Autism

Brain cells grow faster in children with some forms of autism due to distinct changes in core cell signaling patterns, according to research from the laboratory of Anthony Wynshaw-Boris, MD, PhD, chair of the department of genetics and genome sciences at Case Western Reserve University School of Medicine, and a member of the Case Comprehensive Cancer Center. Rapid cell growth can cause early brain overgrowth, a common feature in 20-30% of autistic children. But, the genetics of autistic children vary making it difficult to pinpoint common mechanisms underlying the disease.

“Autism is a complex disorder with multiple genetic and non-genetic factors,” explained Wynshaw-Boris. “Because the causes are diverse, it may help to define a subset of patients that have a common [symptom], in this case early brain overgrowth.”

In a study published in Molecular Psychiatry, Wynshaw-Boris and his colleagues started with skin cell samples from autistic children with enlarged brains and worked backward. Researchers in the laboratory “reprogrammed” donated skin cells to produce cells found in the developing brain including induced pluripotent stem cells and neural progenitor cells. Stem and progenitor cells are important therapeutic tools as they have the potential to grow into a multitude of cell types. The researchers hypothesized that even though the children in the study had different forms of autism, the precursor cells could be used to find common molecular and cellular mechanisms.

The researchers discovered that cells derived from autistic donors grew faster than those from control subjects and activated their genes in distinct patterns. Genes related to cell growth were unusually active, leading to more cells but fewer connections between them. This can cause faulty cell networks unable to properly transmit signals in the brain and enlarged heads during early development.

The researchers identified abnormal genes in the cells grown from autistic donors as belonging to the Wnt signaling pathway. The Wnt genes are critical for cell growth and serve as central players in cell networks, interfacing with multiple signaling pathways. Wynshaw-Boris previously identified the Wnt pathway as related to autism in mouse models of the disease. In a separate study published in Molecular Psychiatry earlier this year, the Wynshaw-Boris laboratory showed mice lacking Wnt genes display autism-like symptoms including social anxiety and repetitive behavior. The researchers could prevent these adult symptoms by treating the mice with medications that activate Wnt signaling in the uterus, during development.

“The Wnt pathway is one of the core developmental pathways conserved from invertebrates to humans. Our studies solidify previous suggestions that this pathway has a role in autism,” said Wynshaw-Boris.

Once they identified the dysfunctional signaling pathway in their reprogrammed autistic samples, the researchers (including the laboratories of Alysson Muotri, PhD at the University of California San Diego and Fred Gage, PhD at the Salk Institute) attempted to correct it by exposing mature nerve cells derived from autistic donors to drug compounds. One drug currently being tested in clinical trials for autism is insulin growth factor 1 (IGF-1). When the researchers added IGF-1 to nerve cells derived from autistic donors, neural networks were reestablished. It is unclear whether the positive effects of IGF-1 were on the Wnt pathway, and the exact compensatory mechanism requires further investigation.

Wynshaw-Boris’s studies in cell culture and mouse models of autism confirm improper Wnt signaling can lead to rapid brain cell growth and brain enlargement in the embryo, resulting in abnormal social behavior after birth. The next step will be to determine which genes are most impacted by Wnt signaling defects during early development, and how these changes result in abnormal behavior. “We would also like to find other drugs or compounds that may slow down the growth of the cells in tissue culture,” said Wynshaw-Boris. Together, these findings may help researchers unravel common ways brain cells can become impaired during early development in carefully chosen subsets of patients and contribute to symptoms across the autism spectrum.

Scientists Keep a Molecule from Moving Inside Nerve Cells to Prevent Cell Death

Amyotrophic lateral sclerosis (ALS, or Lou Gehrig’s disease) is a progressive disorder that devastates motor nerve cells. People diagnosed with ALS slowly lose the ability to control muscle movement, and are ultimately unable to speak, eat, move, or breathe. The cellular mechanisms behind ALS are also found in certain types of dementia.

A groundbreaking scientific study published in Nature Medicine has found one way an RNA binding protein may contribute to ALS disease progression. Cells make RNA to carry instructions for making proteins from DNA to protein-constructing machinery.

The culprit protein, TDP-43, normally binds to small pieces of newly read RNA and helps shuttle the fragments around inside nerve cell nuclei. The study describes for the first time the molecular consequences of misplaced TDP-43 inside nerve cells, and demonstrates that correcting its location can restore nerve cell function. Misplacement of TDP-43 in nerve cells is a hallmark of ALS and other neurological disorders including frontotemporal dementia (FTD), Alzheimer’s, Parkinson’s, and Huntington’s diseases. Studies that characterize common mechanisms behind these diseases could have widespread implications and may also accelerate development of broad-based therapies.

To find the misplaced TDP-43, the researchers viewed nerve cells donated by people who died from ALS or FTD under high powered microscopes. They discovered TDP-43 accumulates in nerve cell mitochondria, critical structures responsible for generating the enormous amount of energy nerve cells require. By physically isolating the affected mitochondria the researchers were able to pinpoint TDP-43’s exact location inside the subcellular structures. They were also able to characterize variations of the protein most likely to get misplaced.

This important work was led by Xinglong Wang, PhD, from the department of pathology at Case Western Reserve University School of Medicine and a team of scientists from his laboratory.

“By multiple approaches, we have identified the mitochondrial inner membrane facing matrix as the major site for mitochondrial TDP-43,” explained Wang. “Mitochondria might be major accumulation sites of TDP-43 in dying neurons in various major neurodegenerative diseases.”

The researchers discovered that once inside the mitochondria, TDP-43 resumes its RNA binding role and attaches itself to mitochondrial genetic material. This disrupts the mitochondria’s ability to generate energy for the cell. Wang’s team was able to precisely identify the RNA in mitochondria that was bound by TDP-43 and observe the resultant disassembly of mitochondrial protein complexes. This finding provides much needed clarity on the consequences of TDP-43 misplacement inside nerve cells and opens the door for deeper studies involving a range of neurological disorders. Although the study focused on ALS and FTD, according to Wang “mislocalization of TDP-43 represents a key pathological feature correlating strongly with symptoms in more than half of Alzheimer’s disease patients.”

Mutations in the gene encoding TDP-43 have long been linked to neurodegenerative diseases like ALS and FTD. Wang’s team found that disease-associated mutations in TDP-43 enhance its misplacement inside nerve cells. The researchers also identified sections of TDP-43 that are recognized by mitochondria and serve as signals to let it inside. These sections could serve as therapeutic targets, as the study found blocking them prevents TDP-43 from localizing inside mitochondria. Importantly, Wang’s team was able to keep TDP-43 out of nerve cell mitochondria in mice using small proteins which “almost completely” prevented nerve cell toxicity and disease progression.

“We, for the first time, provide the novel concept that the inhibition of TDP-43 mitochondrial localization is sufficient to prevent TDP-43-linked neurodegeneration,” said Wang. “Targeting mitochondrial TDP-43 could be a novel therapeutic approach for ALS, FTD and other TDP-43-linked neurodegenerative diseases.”

Wang has begun to develop small proteins that prevent TDP-43 from reaching mitochondria in human nerve cells, and has a patent pending for the therapeutic molecule used in the study.

There is no treatment currently available for ALS or FTD. The average life expectancy for people newly diagnosed with ALS is just three years, according to The ALS Association.

Engineered protein prevents dementia in mice carrying Alzheimer's genes

A newly-developed protein has successfully prevented dementia from occurring in lab mice carrying human Alzheimer’s genes, raising the possibility for development of new treatments for the disease. 

Hanna Lindberg, a researcher at KTH Royal Institute of Technology, worked with colleagues in Sweden and New York to develop a so-called binding protein that could target amyloid beta peptides, which are associated with Alzheimer’s disease.

When equipped with the binding protein, the researchers found that laboratory mice carrying the genes for human Alzheimer’s did not develop disease-related memory impairment or impaired cognitive ability, Lindberg says.

The proteins also prevented the occurrence of amyloid plaques on the brains of lab mice. These plaques result from the large-scale production of amyloid beta peptides in the brains of Alzheimer’s patients.

“We greatly reduced the amounts of amyloid beta peptides in the brains of these mice,” Lindberg says. 

(Image caption: Interaction between affibody-molecules (purple) and amyloid beta (orange). PDB.org: 2OTK)

Binding proteins get their name from their ability to act as an agent in binding molecules together. These proteins mimic the function of antibodies but are much smaller. The proteins used by Lindberg and her team are based on affibodies — an engineered class of proteins that can be designed to bind tightly and specifically against various diseases’ proteins.

“In our case, we have created lots of variations of the same binding protein to find the optimal version for the target peptides which are associated with Alzheimer’s,” Lindberg says.

So far, she says, the results are promising. “The mice that received the treatment with affibody molecules behave just like healthy animals when it comes to memory and cognitive ability,” she says.

The test results could provide the basis for work on new treatments for Alzheimer’s, Lindberg says, adding that a drug could be available within a decade if all the conditions are favorable.

“Alzheimer’s is the most common dementia disease today,” she says. “There are medicines for the symptoms, but no effective treatment method. The medications do not attack the fundamental disease mechanisms, and they tend to become inactive after a while.”

According to the Alzheimer’s Association, 35 million people suffer from Alzheimer’s disease today, and this figure will triple by the year 2050. It usually develops slowly and gradually gets worse as brain function declines and brain cells eventually wither and die. Ultimately, Alzheimer’s is fatal, and currently, there is no cure.

Stefan Ståhl, dean of the School of Biotechnology at KTH and a professor of molecular biotechnology, has been the main supervisor of Hanna Lindberg.

“I recently came home from a project meeting at New York University,” Ståhl says. “It was clear to me that the results achieved by Hanna protein were so good that they are on par with other protein-based preventive medicines that have been used in clinical trials for Alzheimer’s disease. In most cases, these are monoclonal antibodies. No such drugs are on the market today.”

Researchers Discover Novel Factor in Parkinson’s Disease

A team of local researchers have discovered a previously unknown cellular defect in patients with idiopathic Parkinson’s disease, and identified a sequence of pathological events that can trigger or accelerate premature death of certain neurons in the brain seen in this disease.

The findings, published in the journal Nature Communications, will provide a better understanding and further research towards a possible cure of Parkinson’s disease, which is a neurodegenerative disorder that affects movement and other vital functions in nearly one million people in the United States. Despite advances in understanding the causes of familial forms of this disease, the most prevalent idiopathic form of Parkinson’s disease remains a mystery.

Boston University School of Medicine (BUSM) researchers discovered that the cells of people with idiopathic Parkinson’s disease have a previously unknown defect in the function of a specific PLA2g6 protein, causing dysfunction of calcium homeostasis that can determine whether some cells will live or die.

“Idiopathic or genetic dysfunction of calcium signaling triggers a sequence of pathological events leading to autophagic dysfunction, progressive loss of dopaminergic neurons and age-dependent impairment of vital motor functions typical for Parkinson’s disease,“ explained corresponding author Victoria Bolotina, PhD, professor of medicine at BUSM.

“Discovery of this new mechanism associated with human Parkinson’s disease and our ability to mimic this pathology in a novel genetic model opens new opportunities for finding a cure for this devastating neurodegenerative disease,” she added.