Mosquitoes and an evolved taste for humans

In a recent study published in BMC Biology, Dr. Frank Jiggins and his team at the university of Cambridge uncovered the evolutionary history of mosquito migrations and domestication events.

The group found that human-feeding Ae. aegypti mosquitos from an urban population in Senegal, West Africa, were more closely related to populations in Mexico and Sri Lanka than they were to a nearby forest population that fed on animals.

Dr. Jiggins and his team believe that an ancestral population of Ae. aegypti evolved into a human specialist, thus, giving rise to a subspecies known as aegypti aegypti. It is thought that this population migrated out of Africa, therefore explaining why there are such similarities between distant Asian and American populations.

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BMC Biology201715:16; DOI: 10.1186/s12915-017-0351-0

Transplanted Microbes Alter Gut Function and Behavior

Transplantation of fecal microbiota from patients with irritable bowel syndrome (IBS) resulted in IBS-like changes in gut function as well as behavior in recipient mice. Such findings could facilitate development of improved diagnostics as well as effective treatments to replace current symptom-targeting treatments.

The underlying causes of IBS are unknown, which has hindered development of improved diagnostics and therapeutics. The research team, led by Prof. Premysl Bercik and Dr. Stephen Collins of McMaster University (Ontario, Canada) in collaboration with researchers from University of Waterloo (Ontario, Canada), explored effects of fecal microbiota from human IBS patients with diarrhea, with or without anxiety, on gut and brain function in recipient mice. Using fecal transplants, they transferred microbiota from these IBS patients into germ-free mice. The mice developed changes both in intestinal function and behavior reminiscent of the donor IBS patients, compared to mice that were transplanted with microbiota from healthy individuals.

The researchers found that aspects of the illness that were impacted through fecal transplants included gastrointestinal transit (the time it takes for food to leave the stomach and travel through the intestine); intestinal barrier dysfunction; low-grade inflammation; and anxiety-like behavior.

This study “moves the field beyond a simple association, and towards evidence that changes in the microbiota impact both intestinal and behavioral responses in IBS,” said study first author Giada De Palma, research associate at McMaster U.

They authors noted that the study “adds to evidence suggesting that the intestinal microbiota may play some role in the spectrum of brain disorders ranging from mood or anxiety to other problems that may include autism, Parkinson’s disease, and multiple sclerosis.” Further studies are needed to better define the relationship in these conditions. The authors suggested “microbiota-directed therapies, including pre- or probiotic treatment, may be beneficial in treating not only intestinal symptoms but also components of the behavioral manifestations of IBS.”

“Our findings provide the basis for developing therapies aimed at the intestinal microbiota, and for finding biomarkers for the diagnosis of IBS,” said Prof. Bercik.

The study, by De Palma G et al, was published March 1, 2017, in the journal Science Translational Medicine.

Aquamin and Gut Health

Aquamin is a unique Marine multimineral complex, providing bioactive calcium, magnesium and 72 other trace marine minerals, for the fortification of food, beverage and supplement products.

Unlike other mineral sources used in food, beverage and supplement preparation, Aquamin is derived from 100% seaweed, which absorbs trace minerals from the surrounding seawater. This form of absorption, coupled with Aquamins’s unique structure, results in a mineral rich product that is neutral tasting, free of chalky texure and easily absorbed by the human body. Aquamin contains a unique trace mineral profile gained from its marine source. The elements contained are at trace quantities and are insignificant alone, but within a multimineral matrix they work synergistically and give a powerful boost to the action of the calcium and magnesium.

Aquamin is a unique natural ingredient for the enhancement of gut health. It contains significant amounts of calcium and magnesium as well as trace amounts of 72 additional minerals complexed together in a structure engineered by the cell wall of the seaweed lithothamnion sp.

Aquamin has been the subject of 33 peer reviewed publications over the last 10 years, which support its unique health promoting properties.

Aquamin has been shown to enhance gut health by restoring a balanced immune response, promoting the differentiation of colonic cells and providing a balanced gut microflora.

Synthetic bacteria reduce tumor volume in mice

Bacterial cancer therapy (BCT) is an immunotherapy strategy that uses attenuated bacterial strains to suppress tumor growth. While the strains are attenuated, there is still a safety risk associated with their use, and this has prompted investigation into alternative BCT methods. In a recent Science Translational Medicine publication, researchers have actually engineered a bacterium to fight tumors by overexpressing and unlikely protein. In this paper, flagellin protein (FlaB) was overexpressed in Salmonella typhimurium strains. The rationale behind this was that flagellin is known to activate immune responses via Toll-like receptors, specifically TLR5, which would make it a good cancer immunotherapy candidate. These modified bacteria were delivered into tumors in mice, and the impact on tumor volume and TLR signaling was analyzed. The authors discovered that following delivery of the engineered Salmonella, there was a localized increase in immune cells, such as monocytes and macrophages, as a result of TLR4 signaling. Subsequently, the increased immune response inhibited metastasis and tumor growth, further promoting recovery in mice without any deleterious effects from the microbes. Together, these results provide renewed support behind the use of modified bacteria for cancer therapy.

viral communication

Zheng et al. Two-step enhanced cancer immunotherapy with engineered Salmonella typhimurium secreting heterologous flagellin. Science Translational Medicine. 2017. DOI: 10.1126/scitranslmed.aak953

Link Between Air Pollution And Dementia

This article provides an overview of the study conducted to determine if there is a link between airborne particulate matter exposure and pathological brain aging in older women. Older women staying in different regions and not having neurodegenerative disorders were included in the study. The researchers followed the same experimental set up in the mouse models.

Particulate matter (ambient fine particles) with diameter < 2.5µm from traffic emission are a major source of urban pollution, accounting globally for 25% ambient PM.  Epidemiologic studies indicate the association between cognitive deficits with PM exposure in elderly.

Rodent models also indicate long-term neurotoxic effects of air pollutants including memory impairment and selective atrophy, decreased glutamate receptor subunit GluR1, and increased endogenous soluble Aβ. This study was designed to determine if there is a link between PM exposure and Alzheimer’s disease (AD) and related dementias (ADRD) risk.

Study Subjects: A study was conducted on 3647 elderly women, with age between 65 to 79. The women were selected from different regions. Also, the researchers have included the mice model for comparison.

Study Highlights:

  1. Elderly women residing in the areas where the air pollution exceeded the standard levels, were twice as likely to develop dementia, including Alzheimer’s disease (AD).
  2. The study also indicated the women who already had a high genetic predisposition for Alzheimer’s had almost 263% increased risk for the disease.
  3. In animal experiments, mice were exposed to controlled amounts of particulate matter air pollution for 15 weeks. These mice were 60% more likely to have amyloid plaques associated with AD compared to mice not exposed to the pollution.
  4. Fine-particle pollution is a toxic stew of soot, chemical compounds, and other airborne specks no bigger than 2.5 microns in diameter are about 1/28th the width of a human hair.
  5. People living near freeways, ports, and warehouses are exposed to higher amounts because of the diesel exhaust.
  6. The joint data from humans and mice provide the first evidence that the neurodegenerative effect of pollution may involve gene-environment interactions with APOEε4, the major genetic risk factor for pathological brain aging and AD.
  7. A previous research also found that these pollution particles are so tiny that they can move from the blood stream through cell walls and go into our brains. There the particles trigger the immune system response resulting in the formation of plaques associated with neuro-degenerative diseases.

In summary, the study establishes a link between exposure of particulate matter (<2.5µm) and increased risk of dementia. However, the study has a global implication because the pollution knows no border. And thus, more studies in different regions of the world are necessary.

Reference: Cacciottolo, M., et al. “Particulate air pollutants, APOE alleles and their contributions to cognitive impairment in older women and to amyloidogenesis in experimental models.” Translational Psychiatry 7.1 (2017): e1022.

Brain Activity At The Moment of Death

What happens in the brain when we die?

Canadian researchers Loretta Norton and colleagues of the University of Western Ontario examine this grave question in a new paper: Electroencephalographic Recordings During Withdrawal of Life-Sustaining Therapy Until 30 Minutes After Declaration of Death

Norton et al. examined frontal EEG recordings from four critically ill patients at the point where their life support was withdrawn. Here are some details on the four:

 

Here’s the EEG recordings. None of the patients met criteria for brain death at baseline. Time 0 represents the moment of clinical death, namely when arterial blood pressure (ABP) became constant, indicating that the heart had stopped. This occured a few minutes after life support had been withdrawn.

Norton et al. note that for three of the four patients, EEG activity ceased before the heart stopped beating – up to 10 minutes before, in the case of patient #2. However, patient #4 showed a slightly different pattern, with electrical activity (delta wave bursts) occuring up to 10 minutes after the final heartbeat.

The authors say that it’s hard to explain these apparently post-mortem delta waves:

It is difficult to posit a physiological basis for this EEG activity given that it occurs after a prolonged loss of circulation. These waveform bursts could, therefore, be artefactual in nature, although an artefactual source could not be identified.

Another interesting finding was that the actual moment at which the heart stopped was not associated with any abrupt change in the EEG. The authors found no evidence of the large “delta blip” (the so-called “death wave“), an electrical phenomena which has been observed in rats following decapitation.

Overall, this paper is an interesting contribution to the small field of necroneuroscience (see also), although the small sample size and the fact that all of these patients were severely ill, and on heavy sedative medications, makes it hard to know how far the findings will generalize.

Reference:
Norton L, Gibson RM, Gofton T, Benson C, Dhanani S, Shemie SD, Hornby L, Ward R, & Young GB (2017). Electroencephalographic Recordings During Withdrawal of Life-Sustaining Therapy Until 30 Minutes After Declaration of Death. The Canadian Journal of Neurological Sciences, 44 (2), 139-145 PMID: 28231862

The 12 Deadliest Drug-Resistant Bacteria Have Officially Been Ranked

In the face of rising antibiotic resistance, the World Health Organisation (WHO) has published its first ever list of the deadliest superbugs that threaten human health.

This so-called dirty dozen encompasses 12 families of dangerous bacteria that have developed resistance to the drugs used to treat common infections. Antibiotic-resistance costs some 700,000 lives each year, and if the phenomenon can’t be halted, experts predict that the number could grow to 10 million deaths annually by 2050.

“Antibiotic resistance is growing, and we are fast running out of treatment options,” says the WHO’s assistant director-general for health systems and innovation, Marie-Paule Kieny.

“If we leave it to market forces alone, the new antibiotics we most urgently need are not going to be developed in time.”

The list is divided into three urgency categories – critical, high, and medium – representing how badly we need new antibiotics to treat their respective superbugs.

The “critical” section includes three bacteria – Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacteriaceae – which are all resistant to multiple drugs, and can cause a range of serious infections, including pneumonia and blood infections.

These species are all examples of what’s called gram-negative bacteria – bugs that usually live in the gut that have developed two cellular membranes, making it harder for drug molecules to penetrate them.

“So if you can’t get the molecule in, it can’t act and kill the bacteria,” antibiotics researcher Carolyn Shore from Pew Charitable Trusts explained to Kelly Crowe at CBC News.

The nine other pathogens making up the high and medium urgency categories are bacteria that cause more common diseases – such as gonorrhoea and food poisoning – but which can also be deadly, and are increasingly resistant to drugs.

These include methicillin-resistant Staphylococcus aureus (MRSA), Salmonellae, and Haemophilus influenzae.

The list is a grave acknowledgement by the WHO that current pharmaceutical research efforts to curb antibiotic resistance aren’t doing enough to curb the risks posed by these superbugs.

The list “is not meant to scare people about new superbugs, but to signal to researchers and pharmaceutical companies what their priorities should be”, Kieny told media at a press conference in Geneva, Switzerland on Monday.

According to Kieny, one of the problems with producing new antibiotics is they don’t make a lot of profit for pharmaceutical companies,which lowers the incentive to make them.

While antibiotics require a huge amount in terms of research and development costs, they are only taken by patients for a short time, meaning only a small volume is sold.

One solution could be to alter how companies and research institutions are financially rewarded for developing new antibiotics, rather than just generating their profits through products sales.

But for such a system to work, it will take a lot of cooperation from governments around the world.

“This is not a problem that we can solve at a national level, and it is one in which low- and middle-income countries are linked to high-income ones,” antimicrobial specialist Petra Gastmeier from Charité University in Germany told Science.

Here’s hoping the new list provided by the WHO can help nations focus on the right ways to combat these deadly pathogens.

With Kieny estimating new drugs could still be a decade away, the earlier we address this, the better.

The WHO list appears below:

WHO priority pathogens list for R&D of new antibiotics

Priority 1: CRITICAL

1. Acinetobacter baumannii, carbapenem-resistant

2. Pseudomonas aeruginosa, carbapenem-resistant

3. Enterobacteriaceae, carbapenem-resistant, ESBL-producing

Priority 2: HIGH

1. Enterococcus faecium, vancomycin-resistant

2. Staphylococcus aureus, methicillin-resistant, vancomycin-intermediate and resistant

3. Helicobacter pylori, clarithromycin-resistant

4. Campylobacter spp., fluoroquinolone-resistant

5. Salmonellae, fluoroquinolone-resistant

6. Neisseria gonorrhoeae, cephalosporin-resistant, fluoroquinolone-resistant

Priority 3: MEDIUM

1. Streptococcus pneumoniae, penicillin-non-susceptible

2. Haemophilus influenzae, ampicillin-resistant

3. Shigella spp., fluoroquinolone-resistant

The full report is available on the WHO’s website.