TAPEWORM FOUND LIVING INSIDE A PATIENTS BRAIN

A genome of a rare species of tapeworm found living inside a patient's brain has been sequenced for the first time, in research published in the open access journal Genome Biology. The study provides insights into potential drug targets within the genome for future treatments.

A 50-year-old man of Chinese ethnicity was admitted to hospital in the East of England after reporting symptoms of headaches, seizures, altered smell and memory impairment. The patient had lived in the UK for 20 years but visited his homeland often. After testing negative for a range of diseases and not presenting any other abnormalities, doctors began to take a series of MRI images of his brain. Over the course of four years, they noticed a lesion migrate at least 5 cm across his brain, and after taking a biopsy from his left thalamus, they discovered a 1 cm long ribbon-shaped larval worm. The patient, who remains anonymous, was cured of his infection by the operation and is now recovering.

Small samples of the worm were sent to researchers at the Wellcome Trust Sanger Institute, where they began to investigate its genome. Through sequencing its DNA, they identified it as Spirometra erinaceieuropaei, a rare tapeworm species typically found in China, South Korea, Japan and Thailand, and known to cause infection by ingesting undercooked frogs or snakes, using frog meat for treating wounds, and ingesting contaminated water.

The researchers sequenced the worm's entire genome for the first time, measuring it as 1.26 billion base pairs long, which is currently the largest reported genome for any flatworm. This was despite the fact they had such a small sample to work from after removal from the patient's brain. By investigating specific sections of the worm's genome, they were also able to identify genes for resistance to certain treatments, and other potential drugs targets.

Lead author Hayley Bennett from the Wellcome Trust Sanger Institute said: "This infection is so rare worldwide and completely unexpected in this country that the patient was not diagnosed with sparganosis until the worm was pulled out from the brain. We were also surprised at how large the genome was, it is much bigger than those of other known flatworms, and roughly a third of the size of the human genome. By comparing the genome to other tapeworms we can see that certain gene families are expanded -- these possibly underpin this worm's success in a large variety of host species. The data gave us a first look at a whole group of tapeworms that have not been sequenced before."

Through investigating specific parts of the genome for sensitivity to known tapeworm treatments, the researchers found that the tapeworm had genes providing resistance to benzimidazole, but possible sensitivity to another tapeworm drug praziquantel.

The team also investigated the genome to find potential targets which could be exploited by drugs already on the market but known for treating other diseases. They found a number of genes which are targets for known cancer drugs, suggesting that these treatments could be re-purposed for treating this type of infection.

The researchers also identified twenty expanded gene families with unknown function, which they say demonstrates how little is known about this order of tapeworms, and could explain its ability to live in a wide range of hosts (crustaceans, reptiles, amphibians and mammals) as well as in aquatic environments. They have made all their data publicly available so as to help other researchers.

Hayley Bennett said: "We think that it is important to make the genomic data available as is it offers a resource predicting whether other drugs can be repurposed for use in really rare infections such as in this case."

AUTISM NEURONS CONTROLLING SOCIAL BEHAVIOR FOUND

Humans  with autism often show a reduced frequency of social interactions and an increased tendency to engage in repetitive solitary behaviors. Autism has also been linked to dysfunction of the amygdala, a brain structure involved in processing emotions. Now Caltech researchers have discovered antagonistic neuron populations in the mouse amygdala that control whether the animal engages in social behaviors or asocial repetitive self-grooming. This discovery may have implications for understanding neural circuit dysfunctions that underlie autism in humans

This discovery, which is like a "seesaw circuit," was led by postdoctoral scholar Weizhe Hong in the laboratory of David J. Anderson, the Seymour Benzer Professor of Biology at Caltech and an investigator with the Howard Hughes Medical Institute. The work was published online on September 11 in the journalCell.

"We know that there is some hierarchy of behaviors, and they interact with each other because the animal can't exhibit both social and asocial behaviors at the same time. In this study, we wanted to figure out how the brain does that," Anderson says.

Anderson and his colleagues discovered two intermingled but distinct populations of neurons in the amygdala, a part of the brain that is involved in innate social behaviors. One population promotes social behaviors, such as mating, fighting, or social grooming, while the other population controls repetitive self-grooming -- an asocial behavior.

Interestingly, these two populations are distinguished according to the most fundamental subdivision of neuron subtypes in the brain: the "social neurons" are inhibitory neurons (which release the neurotransmitter GABA, or gamma-aminobutyric acid), while the "self-grooming neurons" are excitatory neurons (which release the neurotransmitter glutamate, an amino acid).

To study the relationship between these two cell types and their associated behaviors, the researchers used a technique called optogenetics. In optogenetics, neurons are genetically altered so that they express light-sensitive proteins from microbial organisms. Then, by shining a light on these modified neurons via a tiny fiber optic cable inserted into the brain, researchers can control the activity of the cells as well as their associated behaviors.

Using this optogenetic approach, Anderson's team was able to selectively switch on the neurons associated with social behaviors and those linked with asocial behaviors.

With the social neurons, the behavior that was elicited depended upon the intensity of the light signal. That is, when high-intensity light was used, the mice became aggressive in the presence of an intruder mouse. When lower-intensity light was used, the mice no longer attacked, although they were still socially engaged with the intruder -- either initiating mating behavior or attempting to engage in social grooming.

When the neurons associated with asocial behavior were turned on, the mouse began self-grooming behaviors such as paw licking and face grooming while completely ignoring all intruders. The self-grooming behavior was repetitive and lasted for minutes even after the light was turned off.

The researchers could also use the light-activated neurons to stop the mice from engaging in particular behaviors. For example, if a lone mouse began spontaneously self-grooming, the researchers could halt this behavior through the optogenetic activation of the social neurons. Once the light was turned off and the activation stopped, the mouse would return to its self-grooming behavior.

Surprisingly, these two groups of neurons appear to interfere with each other's function: the activation of social neurons inhibits self-grooming behavior, while the activation of self-grooming neurons inhibits social behavior. Thus these two groups of neurons seem to function like a seesaw, one that controls whether mice interact with others or instead focus on themselves. It was completely unexpected that the two groups of neurons could be distinguished by whether they were excitatory or inhibitory. "If there was ever an experiment that 'carves nature at its joints,'" says Anderson, "this is it."

This seesaw circuit, Anderson and his colleagues say, may have some relevance to human behavioral disorders such as autism.

"In autism," Anderson says, "there is a decrease in social interactions, and there is often an increase in repetitive, sometimes asocial or self-oriented, behaviors" -- a phenomenon known as perseveration. "Here, by stimulating a particular set of neurons, we are both inhibiting social interactions and promoting these perseverative, persistent behaviors."

Studies from other laboratories have shown that disruptions in genes implicated in autism show a similar decrease in social interaction and increase in repetitive self-grooming behavior in mice, Anderson says. However, the current study helps to provide a needed link between gene activity, brain activity, and social behaviors, "and if you don't understand the circuitry, you are never going to understand how the gene mutation affects the behavior." Going forward, he says, such a complete understanding will be necessary for the development of future therapies.

But could this concept ever actually be used to modify a human behavior?

"All of this is very far away, but if you found the right population of neurons, it might be possible to override the genetic component of a behavioral disorder like autism, by just changing the activity of the circuits -- tipping the balance of the see-saw in the other direction," he says.

Salicylates Found In Aspirin May Reduce Neuropathic Pain

Today's post from herald-review.com (see link below) takes a look at the possibility that Salicylates (most commonly found in aspirin) may be able to help control the symptoms of neuropathy by reducing so-called proinflammatory cytokynes (you're going to need to Google that one - not enough space here). Recent research suggests that Salicylates will target these cytokines, thus reducing  the symptoms that make our lives miserable. It's a short article and interesting but you may need to increase your background knowledge through your own research to understand the science behind it. One thing is sure (and the article emphasises this) you should consult with your doctor or neurologist before taking too much aspirin.

Dear Pharmacist: Salicylates may be key to easing neuropathy
SUZY COHEN For the Herald Review Apr 13, 2016

We take for granted the comfort we feel in our hands and feet, but some people have lost that comfort, and they suffer all day long with strange nerve-related concerns. There is new research about aspirin that could help them; but first, let’s talk about that nerve pain, called “neuropathy.”

Neuropathy feels like you are touching or stepping on pins and needles. It can affect you all over, not just your hands and feet. Depending on various factors (race, age, weight, alcohol consumption, insulin and A1c), your experience of neuropathy may also include pain, vibration or buzzing sensations, lightheadedness, burning sensations (even in your tongue), trigeminal neuralgia or cystitis.

Recognizing what your neuropathy stems from is critical to you getting well. For some, it is due to a vitamin deficiency. For example, vitamin B12 or probiotics that help you to manufacture your own B12 in the gut. For others, it could be that wine you drink with dinner because wine is a potent drug mugger of B1 (thiamine) which protects your nerve coating. By a mile, the most common cause of neuropathy is diabetes.

Approximately half of all people with diabetes experience diabetic neuropathies, mainly in the hands and feet. Some doctors will tell you that maintaining healthy blood glucose will reverse neuropathy but that’s not true, we know from The Diabetes Control and Complications Trial that even intensive glucose control is insufficient to control the risk of diabetic neuropathy.

It’s tough love, but I need to say it: Uncontrolled neuropathy can cause a 25 percent higher cumulative risk of leg amputation. So, gaining control is important for your independence. I’ve written about natural supplements for neuropathy in the past (articles are archived at suzycohen.com), and you can have a free ebook “Spices that Heal” which offers more natural advice (get it by signing up for my email newsletter).

New research was published last March in Current Diabetes Reports. Scientists confirmed that targeting inflammatory cytokines can help relieve diabetic neuropathy. Oftentimes, that bad gateway called NF Kappa B (NFKB) opens its floodgates, and spits out proinflammatory cytokines such as COX-2 (Celebrex lowers this), nitric oxide synthase, lipoxygenase, TNF alpha and a lot of pain-causing interleukins (IL-1β, IL-2, IL-6, IL-8).

The researchers reported that something as simple as salicylate therapy could help reduce some of these cytokines as well as circulating glucose, triglycerides, C reactive protein and free fatty acids. When you think of salicylates, please understand this is a broad group of compounds found naturally in the plant kingdom. Salicylate is the main ingredient in aspirin and other analgesics, both prescribed and over-the-counter. Salicylates include spearmint, peppermint (even in mint toothpaste) and in muscle rubs. White willow bark is an herb that is morphed and turned into aspirin. They’re not right for everyone; so please ask your doctor about salicylates for neuropathy. Also ask if you can have a blood test to evaluate some of the proinflammatory markers I noted above.

Suzy Cohen can be reached at www.SuzyCohen.com

http://herald-review.com/news/opinion/editorial/columnists/dear-pharmacist-salicylates-may-be-key-to-easing-neuropathy/article_0549df7f-5c1b-5987-9900-f629df764099.html