Cells use a little-known molecule to protect themselves from iron overload

Amazing stuff! Biological iron is no irony! 😊

Notice the charts in this study are unusually very well done. They tell a consistent story about the function of polyamines.

"... When too much of [iron] is left free inside cells, it can trigger destructive reactions that break down DNA, proteins, and even cell membranes.

Now, ... have discovered that cells rely on an unexpected protector against this threat: small molecules called polyamines.

The researchers’ detailed findings ... reveal that polyamines act like storage lockers for iron, safely holding the metal in a non-reactive state until cells need it.

These findings solve a decades-old mystery about why cells maintain such extraordinarily high levels of polyamines and uncover a previously unknown defense mechanism that protects cells from toxic iron overload. ..."

From the highlights and abstract:

"Highlights

• Genome-wide CRISPR screen identifies polyamine-GPX4 synthetic lethality

• Polyamine depletion raises labile iron and ferritin without altering total iron

• Live-cell labile iron sensor shows inverse coupling with polyamines

• Spermine and spermidine directly coordinate Fe2+ to limit its reactivity

Summary

Polyamines are essential and evolutionarily conserved metabolites present at millimolar concentrations in mammalian cells.

Cells tightly regulate polyamine homeostasis through complex feedback mechanisms, yet the precise role necessitating this regulation remains unclear. Here, we show that polyamines contribute to endogenous buffering of redox-active iron, providing a molecular link between polyamine metabolism and ferroptosis.

Using a genome-wide CRISPR screen, we identified a synthetic lethal dependency between polyamine depletion and the key ferroptosis suppressor, glutathione peroxidase 4 (GPX4).

Mechanistically, we show that polyamine deficiency triggers a redistribution of cellular iron, increasing the labile iron pool and upregulating ferritin.

To directly visualize this iron buffering in living cells, we developed a genetically encoded fluorescent reporter for redox-active iron.

Live-cell analysis revealed a striking inverse correlation between intracellular polyamine levels and redox-active iron at single-cell resolution.

These findings reposition polyamines as key regulators of iron homeostasis, with implications for ferroptosis-linked disease states and cellular redox balance."

Cells use a little-known molecule to protect themselves from iron overload | MIT News | Massachusetts Institute of Technology "This discovery points toward new combination strategies against cancer, and may explain the iron buildup seen in disorders such as early-onset Parkinson’s disease."

Polyamines buffer labile iron to suppress ferroptosis (no public access)

Polyamines buffer labile iron to suppress ferroptosis (preprint, open access)

Graphical abstract

Fig. 1 CRISPR screen identifies modulators of polyamine sensitivity

Fig. 2 Polyamine depletion promotes ferroptosis

Fig 3 Polyamines act independently of canonical ferroptosis regulators

Fig 4 Polyamine deficiency increases redox-active iron

Fig 5 Genetically encoded sensor for redox-active iron

Scientists discover how cells use a secret weapon to fight off some pathogens

Amazing stuff! Did you take your vitamin supplement today?

"Key takeaways

• ... research shows that mitochondria detect invading pathogen Toxoplasma gondii and ramp up competition for vitamin B9, also known as folate, depriving it of the nourishment it needs to grow.
• This new discovery came about when a researcher noticed that the amount of mitochondrial DNA in a mitochondrion increased during an infection.
• The new discovery raises the possibility that a vitamin regimen could rewire mitochondrial metabolism to make it even more effective at preventing infections, such as toxoplasmosis, in people.

...

mitochondria starve pathogens by competing with them for vitamin B9 (folate) to prevent infection. The researchers found that the folate used by mitochondria as part of their normal metabolism reduced the amount of folate available to a specific parasite, Toxoplasma gondii, which subsequently grew more slowly. ..."

From the editor's summary and abstract:

"Editor’s summary

Mitochondria consume nutrients that are also needed by invading pathogens. Whether cells exploit this overlap for host defense has been unclear. Medeiros et al. found that cells harness mitochondrial metabolism to restrict access of the intracellular parasite Toxoplasma gondii to the essential B vitamin folate (see the Perspective by Suomalainen and Nikkanen). When host cells detect intracellular parasite effectors, they activate the integrated stress response and its key effector, ATF4. ATF4 induces one-carbon metabolism processes in host mitochondria that use folate. Because Toxoplasma requires folate to generate thymidine for DNA synthesis, ATF4 activation restricts parasite replication. Thus, infected cells can weaponize mitochondrial metabolism to defend against pathogens. ...

Structured Abstract

INTRODUCTION

Mitochondria ... also use and consume many nutrients that invading pathogens rely on. ...

RATIONALE

... We focused on the replication of mitochondrial DNA (mtDNA), which requires nutrients including those that maintain one-carbon metabolism processes required for nucleotide biosynthesis. We found that infection with the intracellular parasite Toxoplasma gondii increased mtDNA copy number. This response was independent of mitochondrial biogenesis but required activating transcription factor 4 (ATF4), which was activated through the integrated stress response (ISR) kinase HRI in response to parasite effector–induced mitochondrial stress.

RESULTS

Having identified that Toxoplasma infection led to an increase in mtDNA in an ATF4-dependent manner, we next investigated the underlying mechanism. During infection, ATF4 induced the mitochondrial one-carbon enzymes MTHFD2 and SHMT2, which use folate to provide carbon units for biosynthetic pathways, such as nucleotide synthesis. Both ATF4 and MTHFD2 were required for the increase in mtDNA and for restricting parasite growth. We pinpointed this restriction to competition for folate, an essential cofactor that Toxoplasma requires to produce deoxythymidine monophosphate (dTMP) and to proliferate.

Disrupting mitochondrial one-carbon metabolism—through ATF4 loss or methotrexate treatment—led to increased parasite dTMP synthesis and replication. In vivo, preventing ATF4 activation through pharmacological inhibition of the ISR similarly elevated parasite burden.

CONCLUSION

We discovered a host defense strategy rooted in metabolic competition between mitochondria and an intracellular pathogen. This defense was mediated by the ISR effector ATF4, which was activated in response to the detection of parasite effector–induced mitochondrial stress. ATF4 enhanced mitochondrial one-carbon metabolism, thereby depriving Toxoplasma gondii of host folate(s) and limiting its ability to synthesize dTMP and proliferate.

Thus, mitochondria execute a noncanonical metabolic defense against an intracellular pathogen. We propose that these organelles are positioned to compete with other intracellular pathogens for nutrients, such as folate, that are essential for their replication."

Scientists discover how cells use a secret weapon to fight off some pathogens | UCLA "Mitochondria use folate in such quantities that invading Toxoplasma gondii grows more slowly"

Mitochondria protect against an intracellular pathogen by restricting access to folate

Host cells weaponize mitochondrial metabolism.

Scientists develop a second, universal antivenom that neutralizes the neurotoxins of 19 of the world's deadliest snakes in 2025

Good news! Amazing stuff! I blogged here in February about an earlier, universal antivenom!

So now we have to broadly effective universal antivenoms against snake bites, and both came out in 2025!

The hero is Tim Friede [Friede is German for peace]!

"By using antibodies from a human donor [Time Friede] with a self-induced hyper-immunity to snake venom, scientists have developed the most broadly effective antivenom to date, which is protective against the likes of the black mamba, king cobra, and tiger snakes in mouse trials. Described in the journal Cell, the antivenom combines protective antibodies and a small molecule inhibitor and opens a path toward a universal antiserum. ...

"The donor, for a period of nearly 18 years, had undertaken hundreds of bites and self-immunizations with escalating doses from 16 species of very lethal snakes that would normally kill a horse," ..."

From the highlights and abstract:

"Highlights

• We report a systematic method for the construction of a broad-spectrum snake antivenom

• Broadly neutralizing antitoxin antibodies were identified from a venom-immune subject

• Broad toxin neutralization involved recognition of conserved toxin-receptor interfaces

• A 3-agent cocktail blocked envenomation by 19 diverse WHO Category 1 and Category 2 snakes

Summary

Snake envenomation is a neglected tropical disease, with 600 species causing over 100,000 deaths and 300,000 permanent disabilities in humans annually.

Broadly neutralizing antibodies and broad chemical inhibitors have been proposed as solutions, but how to develop a therapeutically effective cocktail and the number of required components have been unclear.

To address this gap, we iteratively recovered two broadly neutralizing antivenom antibodies from the memory B cells of a hyperimmune human donor with extensive snake venom exposure.

The antibodies recognized conserved neutralizing epitopes on prevalent long and short snake neurotoxins, with crystal structures revealing antibody mimicry of the interfaces between these neurotoxins and their host target, the nicotinic acetylcholine receptor.

We combined and tested these antibodies and the phospholipase inhibitor varespladib. A 3-component cocktail rescued animals from whole-venom challenge of all species in a 19-member WHO Category 1 and Category 2 elapid diversity set, with complete protection against most snakes observed."

Scientists develop antivenom that neutralizes the neurotoxins of 19 of the world's deadliest snakes

Snake venom protection by a cocktail of varespladib and broadly neutralizing human antibodies

Graphical abstract

Figure 1 In vivo and in vitro selection for broadly neutralizing antitoxin antibodies

Children’s mattresses and bedroom air can contain/emit toxic chemicals linked with developmental and hormonal disorders

Serious stuff! Concerning, almost shocking! Should this not have been discovered several decades ago? Some of the findings are disturbing e.g. violating existing rules.

Are e.g. flame retardants necessary in children's mattresses and how much of it?

"Children’s mattresses can emit toxic chemicals linked with developmental and hormonal disorders, two new studies have found; high levels of chemicals like phthalates and flame retardants were found near children’s beds, found a study published in Environmental Science & Technology, and a companion study identified mattresses as a key source of exposure. CNN"

From the abstract (1):

"Sleeping microenvironments (SMEs) can expose young children to chemicals of concern.

Using passive samplers, we measured the concentrations of ortho-phthalates (PAEs), organophosphate esters (OPEs), and UV-filters (benzophenones, salicylates, and phenolic benzotriazoles) in the bedroom air, SME, and released from mattresses in 25 bedrooms of children aged 6 months to 4 years in Toronto and Ottawa, Canada.

We detected 28, 31, and 30 compounds in bedroom air, SME air, and mattresses, respectively. SME exceeded bedroom air concentrations, indicating elevated exposure while sleeping and sources from SME contents, with two exceptions.

Higher concentrations of two PAEs and five OPEs (including isomers) in mattress versus SME samplers indicated that mattresses were a source.

Bedding items were likely sources of tris(2-butoxyethyl) phosphate (TBOEP) where SME concentrations were significantly higher than those in mattress samplers.

Older mattresses had higher concentrations of di-2-ethylhexyl phthalate (DEHP) and benzyl butyl phthalate (BzBP).

These results indicate children’s exposure to a range of chemicals of concern while sleeping, at higher concentrations than in their bedrooms.

Practical steps to reduce exposure include limiting items in SMEs such as toys and frequently washing bedding. Also, these results should prompt stricter regulations and greater producer responsibility regarding harmful chemicals used in mattresses and SME articles."

From the abstract (2):

"Our research found that children aged 1–4 years are being exposed to elevated levels of semivolatile organic compounds (SVOCs) in their sleeping microenvironment (SME).

We detected 21 SVOCs in four classes

(ortho-phthalates, 

organophosphate esters, 

benzophenones, and 

salicylates) in 16 new children’s mattresses. 

One mattress exceeded the Canadian regulatory limit of 0.1% (by weight) for children’s mattresses for di-n-butyl phthalate (DnBP), while five had >0.1% diisobutyl phthalate (DiBP), di-n-octyl phthalate (DnOP), and diisononyl phthalate (DiNP), which are regulated in children’s toys but not in mattresses. 

One mattress contained high levels of tris(2-chloroethyl) phosphate (TCEP), which has been prohibited from use in Canada since 2014.

Five mattresses had from 1 to 3% of several organophosphate esters.

No consistent trend was found between the number or concentrations of SVOCs in mattress covers and their polymer type, e.g., rigid polyvinyl chloride vs flexible polypropylene-polyethylene, identified using Fourier transform infrared spectroscopy (FTIR).

Twelve out of 45 SVOCs measured were emitted from eight mattresses tested at room temperature, rising to 20 detected at body temperature, and 21 were detected at body temperature and when body weight was applied.

Given the likelihood of exposure, these results show the need for stricter regulations of all harmful chemicals in children’s mattresses and improved oversight by manufacturers to minimize the use of harmful chemicals, especially when they are not needed."

Global Health NOW: Pandemic Agreement Reached; A Brain Bank Hangs in the Balance; and Spore-Driven Threats

Young Children’s Exposure to Chemicals of Concern in Their Sleeping Environment: An In-Home Study (study no. 1, open access)

Are Sleeping Children Exposed to Plasticizers, Flame Retardants, and UV-Filters from Their Mattresses? (study no. 2, open access)

Graphical abstract (1)

Graphical abstract (2)

These male octopuses inject their female lovers with one of the world’s deadliest toxins

A real Octopussy!  Poison ready for love! Strange love! 😊

"The octopuses in the genus Hapalochlaena, known as blue-ringed octopuses, wield one of the deadliest substances known to science. The tetrodotoxin in their venom is such a potent paralytic that a single bite from the palm-size cephalopods can kill a person. But for the octopuses, it’s just a sedative—one that males use to subdue their much larger mates ...

Sexual cannibalism is common in cephalopods. Females stop eating after laying their eggs and dedicate the rest of their lives to caring for and protecting their developing young. Until then, males are on the menu: Males are much smaller than females so must get up close to insert their specialized sperm-delivering arms, leaving them vulnerable to being eaten midmating. ..."

From the abstract:

"A variety of phylogenetically distant taxa, including flatworms, mollusks, amphibians, and fishes, use the deadly neurotoxin tetrodotoxin (TTX) for predation and defense. A well-known example is the blue-lined octopus, Hapalochlaena fasciata (Hoyle, 1886), which uses symbiotic bacteria to sequester TTX in its posterior salivary glands (PSG)2. When it bites, the TTX-laden saliva immobilizes large prey and has caused lethal envenomation in a few incidents involving humans.

Female blue-lined octopuses are about twice the size of males, which bears the risk of males being cannibalized during reproduction. Surprisingly, we found that the PSG of males is roughly three times heavier than that of females. Using laboratory mating experiments, we show that males use a high-precision bite that targets the female’s aorta to inject TTX at the start of copulation. Envenomating the females renders them immobile, enabling the males to mate successfully."

These octopuses inject their lovers with one of the world’s deadliest toxins | Science | AAAS "Male blue-lined octopuses use venomous bites to avoid becoming their mate’s meal"

Blue-lined octopus Hapalochlaena fasciata males envenomate females to facilitate copulation (no public access)

First potential multi-gas antidote for carbon monoxide, cyanide and hydrogen sulfide poisoning

Good news!

"Researchers have developed a novel antidote to treat hydrogen sulfide poisoning. It is hoped that this innovation will save the lives of workers and rescue personnel. ...

A team ... created the novel therapeutic using artificial haem-model compounds that have a higher affinity for sulfide than human haem. ‘We are trying to synthesise biomedical compounds to mimic the haemoglobin function like the oxygen binding,’ ... This work builds on previous research ..., which identified two complexes that successfully treated carbon monoxide and hydrogen cyanide poisoning in mice. ..."

"... Hydrogen sulfide binds strongly to heme-containing enzymes in the cell and blocks the process of respiration, causing rapid death at higher concentrations. Now, researchers at Kyoto’s Doshisha University have developed an artificial heme-model compound that has a high affinity for hydrogen sulfide and binds to it at a much faster rate than human met-hemoglobin. This compound, met-hemoCD-I, was used to successfully treat hydrogen sulfide-induced toxicity in mice, indicating its potential as an antidote. ..."

From the abstract:

"Hydrogen sulfide is a lethal toxic gas that disrupts cellular respiration in the mitochondrial system. Currently, no antidote is available for the clinical treatment of hydrogen sulfide poisoning. In this study, we investigated the function of iron(III)porphyrin complexes as hydrogen sulfide scavengers in water and evaluated their potential use as therapeutic agents for hydrogen sulfide poisoning. The compounds, named met-hemoCD-P and met-hemoCD-I, are composed of iron(III)porphyrin complexed with per-methylated β-cyclodextrin dimers that contain a pyridine (met-hemoCD-P) or imidazole axial fifth ligand that is coordinated to Fe(III) (met-hemoCD-I). These compounds formed stable HS–Fe(III) complexes under physiological conditions, with binding constants of 1.2 × 105 and 2.5 × 106 M–1 for met-hemoCD-P and met-hemoCD-I, respectively. The binding constant of met-hemoCD-I was 10-times higher than that reported for native human met-hemoglobin at pH 7.4 and 25oC.

Electron paramagnetic resonance (EPR) spectroscopy and H2S quantification assays revealed that after SH– was coordinated to met-hemoCD-I, it was efficiently converted to nontoxic sulfite and sulfate ions via homolytic cleavage of the HS–Fe(III) bond followed by aerobic oxidation.

Mouse animal experiments revealed that the survival rate was significantly improved when NaSH-treated mice were injected with met-hemoCD-I. After the injection, mitochondrial CcO function in brain and heart tissues recovered, and met-hemoCD-I injected was excreted in the urine without chemical decomposition."

First potential antidote for hydrogen sulfide poisoning created | Research | Chemistry World

Research News: A Novel Heme-Model Compound that Treats Lethal Gas Poisoning (original news release) "Researchers from Japan have developed a synthetic, nontoxic antidote to safely treat hydrogen sulfide poisoning"

Detoxification of hydrogen sulfide by synthetic heme model compounds (open access)

Combining an iron porphyrin with a cyclodextrin dimer allowed hydrogen sulfide to be scavenged from the blood of poisoned mice

Sheep earwax can record a toxic diet

What is in your earwax? What else can be found in earwax?

"... The findings add to the team’s previous research showing toxins from different poisonous plants can turn up in cattle earwax. Earwax may be a useful tool for ranchers to quickly locate toxic plants—even pinpointing them to a specific pasture by analyzing the grazing habits of affected animals—and protect their livestock. ...

Researchers are increasingly recognizing earwax as a sticky window into health, though much of this research has focused on humans. Our earwax may show markers of diabetes, cortisol levels, metabolic changes and even cancer. ..."

From the highlights and abstract:

"Highlights

• Zygacine and zygadenine were observed in the earwax of sheep dosed with death camas alkaloids adsorbed onto alfalfa.

• Zygacine and zygadenine were observed in the earwax of sheep that grazed rangeland with abundant death camas.

• Zygacine + zygadenine is a biomarker of death camas (Z. paniculatus) ingestion in the earwax of sheep.

Abstract

Foothill death camas (Z. paniculatus) grows on the foothill ranges of western North America and is acutely toxic to livestock grazing these ranges. The toxic alkaloids in foothill death camas are zygadenine and a series of zygadenine esters, with zygacine, the 3-acetyl ester of zygadenine, being the most abundant. In this study, earwax was evaluated as a specimen to determine livestock exposure to foothill death camas. Death camas alkaloids were detected in the earwax of sheep administered oral doses of foothill death camas alkaloids. In addition, death camas alkaloids were detected in the earwax of sheep that grazed rangeland with abundant death camas.

This study demonstrates the potential of earwax as a noninvasive specimen for chemical analyses to aid in the diagnosis of livestock that may have been exposed to and poisoned by death camas. The results from this study indicate that diagnosticians should analyze for zygacine and zygadenine in the earwax of livestock suspected to have been poisoned by foothill death camas."

Sheep earwax can record a dangerous diet "A quick swab may tell ranchers if their livestock are eating a [toxic] salad on the range"

The evaluation of earwax as a noninvasive specimen to determine livestock exposure to death camas (Zigadenus paniculatus) (no public access)

The death camas, classified as Zigadenus paniculatus by some botanists and Toxicoscordion paniculatum by others, contains two toxic compounds that can cause respiratory, motor, heart and other symptoms in sheep.

Risk Management and 6 months to 8 year phase out for Perchloroethylene (PCE) | US EPA

Is this not another Big Government overreach? 

How dangerous is this substance really that has been in use for such a long time (first synthesized in 1839)?

Do we currently have any better and cheap alternatives?

The EPA calls prohibition a form of risk management! Nice euphemism!

"... EPA has set a 10-year phaseout for the use of PCE in dry cleaning to eliminate the risk to people who work or spend considerable time at dry cleaning facilities. Use of PCE in newly acquired dry-cleaning machines is prohibited after 6 months. Compliance dates for machines that are already owned vary depending on the type of the dry-cleaning machine used, with older types of machines being phased out sooner than newer ones. ..."

Risk Management for Perchloroethylene (PCE) | US EPA

Study reveals key gene protecting plants from harmful metals in soil

Amazing stuff! Could be very useful!

"The negative impact of human activity on Earth doesn’t just affect our planet’s atmosphere—it goes much deeper, into its soils. For instance, excessive application of manure or sewage sludge can increase heavy metal concentrations in agricultural land where vital crops are grown. One of these heavy metals is zinc, a micronutrient necessary for plant and animal health. In excess, however, zinc can be extremely damaging to sensitive plant species. ...
The findings ... reveal that plants tolerate high levels of zinc by trapping it in their root cell walls, a process facilitated by a gene called trichome birefringence or TBR. Scientists and farmers can now use this information to develop and grow crops that are more resilient to soil contamination. ...
A cell wall’s capacity to store zinc is largely dependent on a process called pectin methylesterification—a process that alters the structure of the spongy pectin molecules inside cell walls so that they can absorb more zinc. To better understand this, the researchers performed a genome-wide association study to identify plant genes associated with increased pectin methylesterification. ...
“We found that TBR allele variants influence changes in pectin methylesterification and help determine a plant’s ability to tolerate higher zinc levels,” ..."

From the abstract:

"Zinc (Zn) is an essential micronutrient but can be cytotoxic when present in excess. Plants have evolved mechanisms to tolerate Zn toxicity. To identify genetic loci responsible for natural variation of plant tolerance to Zn toxicity, we conduct genome-wide association studies for root growth responses to high Zn and identify 21 significant associated loci. Among these loci, we identify Trichome Birefringence (TBR) allelic variation determining root growth variation in high Zn conditions. Natural alleles of TBR determine TBR transcript and protein levels which affect pectin methylesterification in root cell walls. Together with previously published data showing that pectin methylesterification increase goes along with decreased Zn binding to cell walls in TBR mutants, our findings lead to a model in which TBR allelic variation enables Zn tolerance through modulating root cell wall pectin methylesterification. The role of TBR in Zn tolerance is conserved across dicot and monocot plant species."

Study reveals key gene protecting plants from harmful metals in soil - Salk Institute for Biological Studies "... scientists find a gene to enhance plants’ zinc tolerance, an important step for producing crops resilient to heavy metals"

Natural variation of TBR confers plant zinc toxicity tolerance through root cell wall pectin methylesterification (open access)

Lotus japonicus sprouts, wildtype (left) and TBR homolog (right), in normal zinc levels (top) and high zinc levels (bottom).

Fig. 2: Natural allelic variation of TBR is associated with root growth responses to high Zn levels.

Dark chocolate and similar cocoa products in the US were found to be contaminated with lead and cadmium. Really!

More bad news for chocoholics like me or junk journalism! Not only is the cocoa harvest this year not very good due to weather and other factors!

This issue is apparently not new since I blogged here in October 2023 about Hershey's issues with heavy metals in their chocolate products.

I am afraid, this is a case of junk journalism! The study actually confirms that the heavy metal content is probably harmless.

What the study suggests is to consume chocolate modestly to avoid any potential negative effects from heavy metals.

I am surprised that this study used only "72 consumer cocoa-containing products" purchased between 2014-2022. This is an extraordinary and extremely small sample!

Furthermore, 70 out of the 72 sample chocolates only contained lead below FDA limits.

"Dark chocolate and similar cocoa products were found to be contaminated with lead and cadmium, per a new study published in Frontiers in Nutrition—with the heavy metals found in both organic and conventionally made chocolate products. CNN"

From the abstract:

"Introduction: 

Contamination of cocoa containing products, such as dark chocolate, with heavy metals including lead, cadmium and arsenic has been reported in the US. However, a formal exploration into the significance of this contamination, nor multi-year trends in the degree or scope remain unresolved.

Methods:

From 2014 to 2022, 72 consumer cocoa-containing products were purchased and analyzed for heavy metal contamination with lead (Pb), cadmium (Cd), and arsenic (As) in 4 distinct cohorts (2014, 2016, 2019, 2022). The thresholds used to assess heavy metal contamination were set to Prop 65 maximum allowable dose levels (MADLs) of 0.5 mcg/day, 4.1 mcg/day, 10 mcg/day for Pb, Cd, and As, respectively.

Results and discussion:

Our analysis reports that 43, 35, and 0% of the products tested exceed Prop 65 MADLs for heavy metal concentrations, respectively, of Pb, Cd, and As, while 97.2% (70 of 72) fall below US FDA IRL limits established for Pb. Median concentrations of each metal tested were lower than even the conservative Prop 65 MADLs, indicating a potentially large effect of product outliers. This indicates that heavy metal contamination—in more than half of products tested—may not pose any appreciable risk for the average person when consumed as a single serving; however, consuming some of the products tested, or more than one serving per day in combination with non-cocoa derived sources heavy metals, may add up to exposure that would exceed the Prop 65 MADLs. Notably, “organic” products were significantly more likely to demonstrate higher levels of both Cd and Pb."

Global Health NOW: An Uptick in Self-Managed Abortions; Dispatches from Sudan’s ‘Humanitarian Desert’; and Inequities in Diabetes-Related Amputations

A multi-year heavy metal analysis of 72 dark chocolate and cocoa products in the USA (open access)

Australian research discovers how common blood thinner can be used as cobra venom treatment

Good news! Probably, many people in Western countries have no or little idea how much snake bites are still a problem in the rest of the world.

"The anticoagulant heparin could be repurposed as a cheap and effective drug to treat cobra bites across Asia and Africa. According to the World Health Organization (WHO), up to 2 million people are envenomed by snakes each year in Asia, while in Africa there are an estimated 435,000 to 580,000 snake bites annually that need treatment.

New Australian research has found the drug can prevent cobra-venom induced necrosis in human cells and mice. Necrosis, the death of tissue around the bite, cannot currently be treated with available antivenoms. ...

They showed heparin treatment could promote human cell survival and inhibit cell death after exposure to different cobra venoms, including the African red (Naja pallida) and black-necked (Naja nigricollis) spitting cobra, the monocled cobra (Naja kaouthia), the Chinese cobra (Naja atra) and the Indian spectacled cobra (Naja naja). ..."

From the editor's summary and abstract:

"Editor’s summary

Snakebite is considered a neglected tropical disease by the World Health Organization, and although antibody-based antivenoms exist, they are species specific, are expensive, and require cold storage as well as intravenous administration in a health care setting. Here, Du and colleagues conducted a whole-genome CRISPR knockout screen to identify genes required for spitting cobra venom cytotoxicity. This screen highlighted genes involved in proteoglycan biosynthesis, suggesting that heparinoids could potentially block spitting cobra venom cytotoxicity. The heparinoid tinzaparin, given subcutaneously at the time of intradermal venom injection, effectively reduced the size of the resulting dermonecrotic lesions in mice, supporting the further evaluation of this drug for the treatment of local tissue damage from spitting cobra envenoming. ...

Abstract

Snakebites affect about 1.8 million people annually. The current standard of care involves antibody-based antivenoms, which can be difficult to access and are generally not effective against local tissue injury, the primary cause of morbidity. Here, we used a pooled whole-genome CRISPR knockout screen to define human genes that, when targeted, modify cell responses to spitting cobra venoms. A large portion of modifying genes that conferred resistance to venom cytotoxicity was found to control proteoglycan biosynthesis, including EXT1, B4GALT7, EXT2, EXTL3, XYLT2, NDST1, and SLC35B2, which we validated independently. This finding suggested heparinoids as possible inhibitors. Heparinoids prevented venom cytotoxicity through binding to three-finger cytotoxins, and the US Food and Drug Administration–approved heparinoid tinzaparin was found to reduce tissue damage in mice when given via a medically relevant route and dose. Overall, our systematic molecular dissection of cobra venom cytotoxicity provides insight into how we can better treat cobra snakebite envenoming."

Common blood thinner can be used as cobra venom treatment

Molecular dissection of cobra venom highlights heparinoids as an antidote for spitting cobra envenoming (open access)

Fig. 5. Snake venom–induced dermonecrosis is inhibited by heparinoids in vivo.

Crop plants Defend Themselves Against toxic Heavy Metals by releasing specialized metabolites into the soil

Amazing stuff!

"... Four years ago [a] team turned to a group of maize-produced metabolites called benzoxazinoids, which act as insecticides and bind iron for plant use and aluminum to reduce its toxicity to plants. In a recent paper, ... demonstrated that benzoxazinoids also bind arsenic, and this improved plant growth in contaminated soil. ... The findings offer potential solutions for farmers in arsenic-contaminated regions. ..."

From the significance and abstract:

"Significance

Toxic levels of arsenic in the soil can substantially reduce crop yields. Here, we reveal a mechanism to reduce plant arsenic accumulation and toxicity. Benzoxazinoids, a dominant class of specialized metabolites (also called secondary metabolites) produced by cereals such as wheat and maize, can reduce arsenic uptake and improve plant performance in the greenhouse and in the field. Furthermore, benzoxazinoid exudation into the soil enhances the performance of subsequent plant generations in soils with high levels of arsenic. This work expands the available genetically encoded resistance strategies to stabilize crop productivity in polluted agroecosystems.

Abstract

By releasing specialized metabolites, plants modify their environment. Whether and how specialized metabolites protect plants against toxic levels of trace elements is not well understood. We evaluated whether benzoxazinoids, which are released into the soil by major cereals, can confer protection against arsenic toxicity. Benzoxazinoid-producing maize plants performed better in arsenic-contaminated soils than benzoxazinoid-deficient mutants in the greenhouse and the field. Adding benzoxazinoids to the soil restored the protective effect, and the effect persisted to the next crop generation via positive plant–soil feedback. Arsenate levels in the soil and total arsenic levels in the roots were lower in the presence of benzoxazinoids. Thus, the protective effect of benzoxazinoids is likely soil-mediated and includes changes in soil arsenic speciation and root accumulation. We conclude that exuded specialized metabolites can enhance protection against toxic trace elements via soil-mediated processes and may thereby stabilize crop productivity in polluted agroecosystems."

Plants Defend Themselves Against Heavy Metals | The Scientist Magazine® A metabolite from maize roots protects the plants against arsenic toxicity.

Root-exuded specialized metabolites reduce arsenic toxicity in maize (open access)

Fig. 2. Soil complementation with benzoxazinoids reduces arsenic toxicity

Universal antivenom for lethal snake toxins in different snakes from Asia and Africa developed by researchers

Good news! Taking the bite out of a snake bite! 

"The discovery of a powerful antibody that neutralizes a key neurotoxin common to four deadly snake species across Asia and Africa marks an important advance in the quest for a universal antivenom against the world’s ~200 venomous snakes; up to 138,000 people die each year from snake bites."

"Researchers have discovered a potent antibody that can neutralize a key type of neurotoxin produced by four different deadly snake species from South Asia, Southeast Asia, and Africa—a step toward an antivenom that could be used on any of the 200 or so dangerous venomous snakes throughout the world.

“We are wiping out a major subclass of neurotoxins here,” ... 

For one thing, snake venoms vary a lot between species, meaning treatment depends on which species has bitten you—which is not always known. Venoms can vary even within species ..."

From the editor's summary and abstract:

"Editor’s summary

Current strategies to treat snakebite envenoming rely on polyclonal antivenom derived from animals such as horses. Although these treatments can be life-saving, they can also result in serum sickness and anaphylaxis, and they require identification of the species of snake behind the bite. To address these limitations, Khalek et al. used a synthetic human antibody library to find and optimize a monoclonal antibody that could neutralize long-chain three-finger α-neurotoxins produced by the Elapidae family of snakes, which includes cobras, kraits, and mambas. The antibody was able to confer protection against envenoming in mice and functioned by mimicking the binding between the toxins and their receptors. This antibody and the approach used to find it represent a step forward on the path toward a universal, optimized antivenom. ...

Abstract

Snakebite envenoming is a major global public health concern for which improved therapies are urgently needed. The antigenic diversity present in snake venom toxins from various species presents a considerable challenge to the development of a universal antivenom. Here, we used a synthetic human antibody library to find and develop an antibody that neutralizes long-chain three-finger α-neurotoxins produced by numerous medically relevant snakes. Our antibody bound diverse toxin variants with high affinity, blocked toxin binding to the nicotinic acetylcholine receptor in vitro, and protected mice from lethal venom challenge. Structural analysis of the antibody-toxin complex revealed a binding mode that mimics the receptor-toxin interaction. The overall workflow presented is generalizable for the development of antibodies that target conserved epitopes among antigenically diverse targets, and it offers a promising framework for the creation of a monoclonal antibody–based universal antivenom to treat snakebite envenoming."

Universal antivenom for lethal snake toxins developed by researchers

Powerful new antivenom raises hopes for a universal solution to lethal snakebites Synthetic antibody neutralizes a key neurotoxin in different snakes from Asia and Africa

Johns Hopkins Bloomberg School of Public Health: Global Health NOW

Synthetic development of a broadly neutralizing antibody against snake venom long-chain α-neurotoxins (open access)

Fig. 1. Cross-reactive anti–3FTx-L mAbs were isolated from a naive [???] library.

Consumer Reports Urges Hershey’s again to Get Heavy Metals Out of Chocolate Products. Really!

Bad news for chocoholics? You wonder about other brands. How does this compare to other food products?

Apparently Consumer Reports reported something similar last year! CR does not explain or hint how the heavy metals get into the chocolate.

CR used California standards, which may be unnecessarily or excessively strict!

I did not read the whole news release, but it appears that actually most products had less heavy metals than the threshold level. So perhaps this is more shock and awe or an attention grabber than real. Or in other words, was this more or less a publicity stunt?

"... Hershey’s milk chocolate, an iconic Halloween treat, had the highest levels of lead in CR’s tests. Last year, CR found that a number of Hershey’s dark chocolate bars had some of the highest levels of lead or cadmium of all brands it tested.  ...
To assess the risk from lead and cadmium, CR looked at whether a serving of each product would expose someone to California’s standard maximum allowable dose levels (MADL) for lead (0.5 micrograms per day) and cadmium (4.1 micrograms per day). ..."

Consumer Reports Urges Hershey’s to Get Heavy Metals Out of Chocolate Products - Consumer Reports Latest CR Tests Find Concerning Levels of Lead in Hershey’s Cocoa Powder and Milk Chocolate; Previous Tests Found Hershey’s Dark Chocolate High in Lead and Cadmium

Credits: Johns Hopkins Bloomberg School of Public Health: Global Health NOW

Seeadler in den USA: Was vergiftet das Wappentier?

Empfehlenswert! Neues, natürliches Nervengift und neue Cyanobakterien! Eingeschleppte, invasive Wasserpflanze und deren Herbizide! Komplex! 

Seeadler in den USA: Was vergiftet das Wappentier? Seit fast 30 Jahren verenden zahlreiche Tiere in Nordamerika an einem natürlichen Nervengift. Auch der Weißkopfseeadler, das amerikanische Wappentier, ist betroffen. Nun weiß man mehr über das Umweltgift.

Ancient antidotes

Very recommendable! Thanks to the advances of modern forensics killing by poisoning has become a rather rare event, but until the not so distant past it was very common to get rid of someone by poisoning whether among commoners or among nobility!

"... His name was Mithridates VI (c.132–63 BCE) and, like his father before him, he became King of Pontus, a state along the Black Sea. Mithridates’ fears spurred him to action – both as poisoner and poison scholar. Mithridates has been called the first experimental toxicologist, with his primary goal being the creation of ‘a “universal antidote” to make himself and his friends immune to all poisons and toxins’. His experimental methods would now be considered dubious at best, including self-dosing with poisons and their supposed antidotes. His practice of taking a bit of poison regularly toward acquiring a tolerance bears his name – mithridatism. ..."

Ancient antidotes | Opinion | Chemistry World Favourites of emperors and royalty, theriacs were the universal cures of their day