Rosa Rubicondior: Malevolent Design

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Thursday, 12 December 2024

Malevolent Design - The Sneak Tactics of Toxoplasma gondii

Toxoplasma gondii parasite uses unconventional method to make proteins for evasion of drug treatment

Here we are with yet another example of an organism that, if there is a designer behind it, that designer can only be described as malevolent and determined to maximise the suffering and misery in the world.

It is, of course, another example of a nasty little parasite which, if you subscribe to the creationist view that complexity 'proves' design, has been designed to ensure we are as vulnerable to is as possible by helping it evade the immune system and other mechanisms, supposedly designed by the same designer god to protect us from the parasites it designs to harm us.

This example is the parasite Toxoplasma gondii, which is notorious for manipulating its natural victims, which are felines and their prey species. For example, mice infected with T. gondii lose their fear of cats so they get eten and the parasite gets into its primary host; infected chimpanzees develop a liking for the smell of leopard urine.

Humans are not the natural secondary host, but the parasite readily infects us as we catch it from cats. It is thought that about one third of humans are infected. Once infected it is impossible to get rid of from the body because, even if antibodies are produced by our immune system, the parasites go into a dormant state as cysts which can form in any organs of the body, including the brain.

Toxoplasma gondii, it's evolution and its pathology in humans. Toxoplasma gondii: Overview, Evolution, and Pathology in Humans

Toxoplasma gondii is a protozoan parasite that infects warm-blooded animals, including humans, but primarily completes its life cycle in felines. It is a member of the phylum Apicomplexa, which includes other parasitic organisms such as Plasmodium (responsible for malaria). The parasite is notorious for its widespread prevalence and potential to cause severe disease in immunocompromised individuals and during pregnancy.
Evolutionary History

Toxoplasma gondii evolved from a common ancestor shared with other apicomplexans. Its evolutionary journey highlights adaptations for survival in both definitive (cat) and intermediate (other animals) hosts.

Apicomplexan Origin:

The phylum likely evolved from free-living photosynthetic algae.
The apicoplast, a remnant plastid, is a key organelle in T. gondii, crucial for fatty acid synthesis and other metabolic functions.

Host Adaptations:

Unlike its relatives with narrow host ranges, T. gondii evolved to infect a vast array of intermediate hosts. This adaptability is attributed to its ability to form hardy oocysts that can survive in the environment and tissue cysts that persist in hosts.

Clonal Lineages:

Population studies show three predominant clonal lineages (Types I, II, III), which emerged around 10,000 years ago, likely through a genetic bottleneck. These lineages exhibit differences in virulence and geographic distribution.

Lifecycle

Sexual Stage:

Occurs only in the intestines of felines, the definitive host. Cats excrete oocysts in their faeces.

Oocysts:

Environmentally resilient and infectious after sporulation, oocysts can contaminate food, water, and soil.

Intermediate Hosts:

Oocysts are ingested by other animals (e.g., rodents, birds, and humans). The parasite then forms tachyzoites (rapidly dividing forms) and bradyzoites (slowly dividing cyst forms) in tissues like the brain and muscles.

Transmission to Cats:

Cats are infected when they eat intermediate hosts harbouring tissue cysts, perpetuating the lifecycle.

Pathology in Humans

Humans typically acquire T. gondii through undercooked meat, contaminated water, or contact with infected cat faeces. Most infections are asymptomatic, but in certain populations, the parasite can cause significant disease.

Acute Toxoplasmosis:

Symptoms: Flu-like symptoms (fever, swollen lymph nodes, fatigue).
Immune response usually controls the infection, leading to cyst formation.

Latent Infection:

Tissue cysts persist, primarily in the brain and muscles, remaining dormant unless the immune system is compromised.

Immunocompromised Individuals:

Reactivation of latent infection can cause life-threatening conditions, such as toxoplasmic encephalitis, especially in individuals with HIV/AIDS or undergoing chemotherapy.

Congenital Toxoplasmosis:

If a woman acquires the infection during pregnancy, the parasite can cross the placenta, causing miscarriage, stillbirth, or severe congenital abnormalities (e.g., hydrocephalus, blindness, mental impairment).

Neurological and Behavioural Effects:

Emerging research suggests T. gondii might influence behaviour and mental health. It has been associated with altered risk-taking, neuropsychiatric disorders like schizophrenia, and changes in personality traits, though causation remains under investigation.

Diagnosis and Treatment

Diagnosis:

Serological tests detect specific IgM and IgG antibodies.
PCR assays can identify parasite DNA, particularly in congenital infections.

Treatment:

Acute infections: Combination therapy with pyrimethamine and sulfadiazine, supplemented with folinic acid to prevent folate depletion.
Chronic latent infections usually do not require treatment unless reactivated.

Control and Prevention

Hygiene: Proper handwashing after handling soil, cats, or raw meat.
Cooking Practices: Ensure meat is thoroughly cooked to destroy tissue cysts.
Cat Care: Regular cleaning of litter trays and preventing cats from hunting can reduce environmental contamination.
Toxoplasma gondii remains a fascinating and medically important organism due to its evolutionary ingenuity, widespread distribution, and complex interactions with hosts, including humans.

How they do this is the subject of a paper in the Journal of Biological Chemistry by researchers from Indian University School of Medicine and a news release by Indiana University.

Toxoplasma gondii parasite uses unconventional method to make proteins for evasion of drug treatment
A study by Indiana University School of Medicine researchers sheds new light on how Toxoplasma gondii parasites make the proteins they need to enter a dormant stage that allows them to escape drug treatment. It was recently published with special distinction in the Journal of Biological Chemistry.
Toxoplasma gondii is a single-celled parasite that people catch from cat faeces, unwashed produce or undercooked meat. The parasite has infected up to one-third of the world's population, and after causing mild illness, it persists by entering a dormant phase housed in cysts throughout the body, including the brain.

Toxoplasma cysts have been linked to behaviour changes and neurological disorders like schizophrenia. They can also reactivate when the immune system is weakened, causing life-threatening organ damage. While drugs are available to put toxoplasmosis into remission, there is no way to clear the infection. A better understanding of how the parasite develops into cysts would help scientists find a cure.

Through years of collaborative work, IU School of Medicine Showalter Professors Bill Sullivan, PhD, and Ronald C. Wek, PhD, have shown that Toxoplasma forms cysts by altering which proteins are made. Proteins govern the fate of cells and are encoded by mRNAs.

But mRNAs can be present in cells without being made into protein. We've shown that Toxoplasma switches which mRNAs are made into protein when converting into cysts.

Professor William J. Sullivan Jr., Corresponding author
Department of Pharmacology & Toxicology
Indiana University School of Medicine
Indianapolis, Indiana, USA.
Lead Author Vishakha Dey, PhD, a postdoctoral fellow at the IU School of Medicine and a member of the Sullivan lab, examined the so-called leader sequences of genes named BFD1 and BFD2, both of which are necessary for Toxoplasma to form cysts.

mRNAs not only encode for protein, but they begin with a leader sequence that contains information on when that mRNA should be made into protein.

Dr. Vishakha Dey, lead author.

Department of Pharmacology & Toxicology
Indiana University School of Medicine
Indianapolis, Indiana, USA.
All mRNAs have a structure called a cap at the beginning of their leader sequence. Ribosomes, which convert mRNA into protein, bind to the cap and scan the leader until it finds the right code to begin making the protein.

What we found was that, during cyst formation, BFD2 is made into protein after ribosomes bind the cap and scan the leader, as expected. But BFD1 does not follow that convention. Its production does not rely on the mRNA cap like most other mRNAs.

Dr. Vishakha Dey.

The team further showed that BFD1 is made into protein only after BFD2 binds specific sites in the BFD1 mRNA leader sequence. Sullivan said this is a phenomenon called cap-independent translation, which is more commonly seen in viruses.
Finding it in a microbe that has cellular anatomy like our own was surprising. It speaks to how old this system of protein production is in cellular evolution. We're also excited because the players involved do not exist in human cells, which makes them good potential drug targets.

Professor William J. Sullivan Jr.
The Journal of Biological Chemistry featured the new study as an "Editor's Pick" paper, which represent a select group of the journal’s publications judged to be of exceptionally high quality and broad general interest to their readership.

This paper describes a mechanism by which a parasite that causes toxoplasmosis in humans can respond to stress and allow the parasite to thrive. The discovery of this mechanism provides a basis for treating these infections. Moreover, a similar mechanism is important in cancer, suggesting that it may be a therapeutic target for multiple human diseases.

Professor George N. DeMartino, PhD, associate editor of the Journal of Biological Chemistry
University of Texas Southwestern Medical Center.

Additional co-authors on the study include IU School of Medicine's Michael Holmes, PhD, and Matheus S. Bastos, PhD. The work was funded by the National Institutes of Health and the Showalter Foundation.

Translational control mechanisms modulate the microbial latency of eukaryotic pathogens, enabling them to evade immunity and drug treatments. The protozoan parasite Toxoplasma gondii persists in hosts by differentiating from proliferative tachyzoites to latent bradyzoites, which are housed inside tissue cysts. Transcriptional changes facilitating bradyzoite conversion are mediated by a Myb domain transcription factor called BFD1, whose mRNA is present in tachyzoites but not translated into protein until stress is applied to induce differentiation. We addressed the mechanisms by which translational control drives BFD1 synthesis in response to stress-induced parasite differentiation. Using biochemical and molecular approaches, we show that the 5′-leader of BFD1 mRNA is sufficient for preferential translation upon stress. The translational control of BFD1 mRNA is maintained when ribosome assembly near its 5′-cap is impaired by insertion of a 5′-proximal stem-loop and upon knockdown of the Toxoplasma cap-binding protein, eIF4E1. Moreover, we determined that a trans-acting RNA-binding protein called BFD2/ROCY1 is necessary for the cap-independent translation of BFD1 through its binding to the 5′-leader. Translation of BFD2 mRNA is also suggested to be preferentially induced under stress but by a cap-dependent mechanism. These results show that translational control and differentiation in Toxoplasma proceed through cap-independent mechanisms in addition to canonical cap-dependent translation. Our identification of cap-independent translation in protozoa underscores the antiquity of this mode of gene regulation in cellular evolution and its central role in stress-induced life-cycle events.

Abbreviations

AP2apetala-2BFD1Bradyzoite Formation Deficient-1BRBinding RegionCDSprotein-coding sequenceFLucfirefly luciferaseNLucNano luciferaseRLURelative Luciferase UnitsuORFsupstream open reading frames

Cellular adaptation and differentiation processes in response to cellular stresses are initiated by reprogramming of gene expression. A central feature of this reprogramming is the rapid lowering of global protein synthesis in favor of selective translation of a subset of mRNAs that include transcription factors that activate genes for stress remediation or differentiation (1, 2, 3). We have shown that this paradigm governs life cycle stage transitions in protozoan parasites that underlie transmission and pathogenesis of infectious disease (3, 4, 5). The study of translational control in these early-branching eukaryotes not only promises to reveal potential novel drug targets but also sheds important mechanistic insights into the evolutionary origins of these regulatory processes (6, 7, 8).

Toxoplasma gondii is an obligate intracellular parasite of warm-blooded animals that causes opportunistic disease in humans. Upon ingestion, the parasites transform into a rapidly replicative stage (tachyzoite) that disseminates throughout the host body before converting into a quiescent stage (bradyzoite) housed in tissue cysts that can be sustained for the life of the host. Tissue cysts are a major route of transmission through the consumption of raw or undercooked meat (9). Reactivation of bradyzoites can occur when patients become immunocompromised, producing life-threatening damage to critical areas where tissue cysts typically reside, such as the brain, heart, and skeletal muscle (10). Current treatments of toxoplasmosis only target replicating tachyzoites and do not appear to exert appreciable activity against the formation or viability of tissue cysts (11). The formation of latent tissue cysts allows Toxoplasma to persist in its host and prevents a radical cure of this infection.

Given the importance of bradyzoites in driving parasite transmission and chronic disease, much research is aimed at understanding the molecular mechanisms orchestrating the conversion between tachyzoites and bradyzoites (12). Differentiation between life cycle stages requires the reprogramming of gene expression, while chromatin remodeling machinery and several apetala-2 (AP2) factors have been shown to contribute to the transcription of bradyzoite-inducing genes (13). Recently, Lourido and colleagues identified a “master regulator” transcription factor termed BFD1 (Bradyzoite Formation Deficient-1) that is necessary and sufficient for bradyzoite formation (14).

BFD1 is a SANT/Myb-like DNA-binding protein whose mRNA is present in tachyzoites but not translated until parasites are exposed to a bradyzoite-induction stress (14). We previously suggested with polysome profiling that BFD1 mRNA is preferentially translated when tachyzoites are subjected to a stress that induces bradyzoite differentiation (15). These studies indicate that expression of BFD1 protein is predominantly regulated by translational control and the elevated levels of BFD1 are sufficient to confer transcription events directing cyst formation. Consistent with this idea, the 5′-leader sequence of BFD1 mRNA is about 2.7 kb in length, harboring multiple predicted upstream open reading frames (uORFs), which are known in other model systems to regulate start codon selection and translation efficiency of the protein-coding sequence (CDS) (16). Moreover, a CCCH-type zinc finger mRNA-binding protein called BFD2 (also referred to as ROCY1) has recently been described that is suggested to direct the stress-dependent translation of BFD1 (17, 18).

Bulk cellular translation begins with eIF4F association with the 5′-cap of mRNAs through its eIF4E subunit, which then recruits the ribosomal preinitiation complex that proceeds to scan the 5′-leader for an optimal start codon (19). This cap-dependent translation can be modulated by uORFs that can be bypassed by scanning ribosomes or allow for re-initiation for efficient CDS translation (20). Cap-independent mechanisms have also been described, most commonly among viruses and less frequently for cellular mRNAs (21, 22, 23). Translation that can occur independent of eIF4E cap association and the subsequent ribosome scanning typically involves direct entry of ribosomes onto the 5′-leader sequence by secondary structures that interface with trans-acting proteins to recruit initiating ribosomes (22, 23).

In this study, we addressed the mechanisms of preferential translation of BFD1 during stress-induced bradyzoite differentiation. Utilizing luciferase reporter assays and genetically modified Toxoplasma parasites, we show that BFD1 translation can occur through a cap-independent mechanism that involves BFD2 binding to the 5′-leader sequence. By comparison, preferential translation of BFD2 during stress occurs by cap-dependent processes. Our results represent the first evidence of cap-independent translation in protozoa, suggesting that it is an ancient mechanism of gene regulation present in early-branching eukaryotes and is critical for directing differentiation in the Toxoplasma life cycle.

We can, of course, dismiss Michael J. Behe's biologically nonsensical excuse of 'devolution' from some presupposed initial perfection because any change which makes an organism better at producing descendants is classically evolutionary and it take mental gymnastics to a new hight of absurdity to believe that something better is less perfect than what preceded it.

So, as always, what creationists need to find the moral and intellectual courage to address is the question of evil and why their supposed creator creates these nasty little parasites that are responsible for so much suffering and misery in the world. Are they just the result of incompetent design or the malevolent design of an omnipotent, omniscient designer? Or are they the result of a mindless natural process?

Malevolent Design - How Malaria Is Being Redesigned to Keep On Killing Children

Study uncovers first evidence of resistance to standard malaria treatment in African children with severe malaria

In another twist of the arms race with human medical science Plasmodium falciparum, the malevolently designed parasite that causes malaria and kills hundreds of thousands of children a year, mostly in Africa, has developed resistance to Artemisinin. Scientists were already aware that resistance had arisen in cases of uncomplicated malaria, but this is the first such incidence of resistance in the more severe form of the disease.

Indiana University School of Medicine researchers, in collaboration with colleagues at Makerere University in Uganda have discovered a case of complicated malaria in a child in Uganda.

Mallevolent Design - How Salmonella Sneaks Past Our Defences To Make Us Sick

Intestinal lumen

New study shows how salmonella tricks gut defenses to cause infection

There is a simple paradox at the heart of creationism that I have never even seen an attempt to resolve. It all comes from two beliefs: there is only one designer god capable of designing living organisms and that designer god designed us complete with our immune system with which we can attempt to resist attack by pathogens, and that pathogens are not the work of this design, but are the result of 'genetic entropy' and 'devolution' since Adam & Eve let 'sin' into the world. The fact that Michael J. Behe, who invented that excuse, has let slip that ID Creationism is Bible literalism in a lab coat seems to be lost on his followers who still dutifully insist that it is a scientific alternative to evolution and should be taught in school science class (presumably now with the tale of Adam & Eve taught as real history and 'sin' as a real force in science).

The paradox is, did the designer god give Adam & Eve an immune system, or did it design an upgrade when 'sin' allowed pathogens to exist? If the former, it was anticipating and planning for the so-called 'fall'; if the latter, it lacked foresight so is not omniscient.

But however creationists resolve this paradox they still have to explain why the 'intelligently designed' immune system doesn't work very well and why whatever is designing pathogens seems to be able to overcome it.

The nonsense about 'sin', 'the fall', etc., is trivially easy to refute because any improvement in a parasite's ability to parasitise its host can't possibly be regarded as a devolution from some assumed initial perfection because an improvement can't be worse that what it's an improvement on. The whole nonsense of 'devolution' is biological gobbledygook, intelligently designed to appeal to scientifically illiterate simpletons who want to fit the Bible superstition somewhere in the reasoning without bothering too much about the logic or the biology.

So, the paradox boils down to why an intelligent designer would be having an arms race with itself so the parasites it creates can continue to parasitise the victims it creates complete with their immune system it created to stop them. Creationists normally flee in terror at the mere mention of arms races, which is why you'll never see them discussed in the cult literature apart from where pathogens are waved aside as 'caused by sin', blah, blah, blah...
So, it would be refreshing indeed to see a genuine attempt by an intelligent design creationist try to give some rational explanation, and hopefully without giving away the fact that ID creationism is merely Christian fundamentalism in disguise, for the discovery by a new UC Davis Health study that shows how the Salmonella bacteria, a major cause of food poisoning, can invade the gut even when protective bacteria are present.

As an added embarrassment for creationists, Salmonella is closely related to Escherichia coli (E.coli) that they usually cite Michael J. Behe as 'proving' it must have been designed by their god because its flagellum is 'irreducibly complex'.

First a little AI background information about Salmonella, where it came from and what it does to us:

Tell me all about Salmonella, please. Salmonella is a genus of bacteria that is commonly associated with foodborne illnesses in humans and animals. These bacteria are known for causing a range of conditions, from mild gastroenteritis to more severe diseases like typhoid fever. Here's an overview of Salmonella:

What is Salmonella?
Salmonella are rod-shaped, Gram-negative bacteria belonging to the family Enterobacteriaceae. They are facultative anaerobes, meaning they can grow in both oxygen-rich and oxygen-poor environments.

Types of Salmonella
Salmonella is classified into two broad categories based on the diseases they cause:

Non-typhoidal Salmonella (NTS):

Causes salmonellosis, a common form of food poisoning.

Found in many animals, including poultry, cattle, reptiles, and amphibians.

Symptoms include diarrhea, fever, abdominal cramps, and vomiting.

Typhoidal Salmonella:

Includes Salmonella Typhi and Salmonella Paratyphi, which cause typhoid and paratyphoid fever, respectively.

These infections are severe, systemic diseases primarily transmitted through contaminated water or food.

How is Salmonella Transmitted?

Foodborne: Consuming undercooked or contaminated meat (especially poultry), eggs, or dairy products.

Waterborne: Drinking contaminated water.

Contact: Handling animals or surfaces contaminated with Salmonella, such as pet reptiles or farm animals.

Person-to-Person: Rare but possible in cases of poor hygiene, especially among caregivers.

Symptoms of Salmonella Infection
The symptoms vary based on the type:

Salmonellosis (non-typhoidal): Appears 6-72 hours after exposure; lasts 4-7 days.

Diarrhea

Fever

Abdominal cramps

Nausea and vomiting

Typhoid Fever: Develops gradually over 1-2 weeks.

High fever

Weakness

Abdominal pain

Rose-colored spots on the skin

Constipation or diarrhea

Risk Groups

Infants, young children, and the elderly.

People with weakened immune systems, such as those with HIV or undergoing chemotherapy.

Travelers to regions with poor sanitation.

Diagnosis

Laboratory Testing: Stool, blood, or urine samples are tested for the presence of Salmonella.

Serotyping: Identifies specific Salmonella strains, useful for outbreaks and epidemiological studies.

Treatment

Non-typhoidal Salmonella: Often self-limiting; hydration is crucial. Antibiotics are usually unnecessary unless the infection spreads beyond the intestines.

Typhoidal Salmonella: Requires prompt antibiotic treatment, such as ciprofloxacin or azithromycin. Severe cases may require hospitalization.

Prevention

Food Safety:

Cook meat and eggs thoroughly.

Avoid cross-contamination between raw and cooked foods.

Wash fruits and vegetables well.

Store food at proper temperatures.

Hygiene:

Wash hands frequently, especially after handling animals or raw foods.

Sanitize surfaces and utensils.

Vaccination:

Vaccines are available for Salmonella Typhi for travelers to high-risk areas.

Pet Precautions:

Avoid contact with reptiles or amphibians, especially for children under five.

Global Impact

Non-typhoidal Salmonella: A leading cause of foodborne illnesses worldwide.

Typhoid Fever: Endemic in many developing countries, with poor sanitation contributing to its prevalence.

Interesting Facts

Salmonella is named after American scientist Daniel Elmer Salmon, though it was first discovered by Theobald Smith in 1885.

These bacteria can survive on dry surfaces for weeks and in water for months.

What is known about the evolutionary origins of the genus and their relationship to other genera?

The genus Salmonella has a fascinating evolutionary history that reflects its adaptation to a wide range of hosts and ecological niches. Here's an overview of what is known about its evolutionary origins and relationships with other genera:

Evolutionary Origins

Family and Order:

Salmonella belongs to the family Enterobacteriaceae and the order Enterobacterales. This group includes other genera such as Escherichia, Klebsiella, Yersinia, and Shigella.

These bacteria are believed to have a common ancestor that lived in the intestinal tracts of primitive animals hundreds of millions of years ago.

Divergence from Common Ancestor:

Genomic analyses suggest that Salmonella diverged from its closest relative, Escherichia coli, approximately 100–150 million years ago. This divergence was likely driven by adaptation to different ecological niches and hosts.

Salmonella has specialized in both intestinal and systemic infections, while E. coli primarily remained a commensal organism with occasional pathogenic strains.

Genomic Evolution

Horizontal Gene Transfer (HGT):

A significant driver of Salmonella's evolution has been the acquisition of genes through horizontal gene transfer. This process introduced:

Virulence genes (e.g., pathogenicity islands).

Antibiotic resistance genes.

These acquisitions allowed Salmonella to colonize new hosts and environments.

Pathogenicity Islands:

The genome of Salmonella contains specialized regions called Salmonella Pathogenicity Islands (SPIs) that encode genes crucial for infection.

SPIs are thought to have been acquired from other bacteria through HGT and are absent in its close relatives, such as E. coli.

Adaptive Evolution:

Salmonella has developed mechanisms to survive harsh conditions, such as the acidic environment of the stomach or macrophage phagosomes. Genes encoding acid resistance and intracellular survival are key to this adaptation.

Speciation and Lineage Divergence

The genus Salmonella is divided into two main species:

Salmonella enterica: The most diverse and widespread species, with six subspecies and over 2,500 serovars.

Salmonella bongori: Found primarily in cold-blooded animals, such as reptiles.

Host Adaptation:

Salmonella enterica has evolved to infect a wide range of warm-blooded and cold-blooded hosts, whereas S. bongori remains restricted to reptiles.

Within S. enterica, specific serovars have adapted to particular hosts (e.g., S. Typhi for humans and S. Dublin for cattle).

Relationship to Other Genera

Closest Relatives:

Escherichia coli: Shares a common ancestor with Salmonella. The two genera are highly similar at the genomic level but differ significantly in pathogenicity and host adaptation.

Shigella: Genetically very similar to E. coli but evolved independently to cause invasive infections.

Phylogenetic Placement:

Within Enterobacteriaceae, Salmonella is part of a subgroup that includes pathogens like Shigella and Yersinia.

Comparative genomics shows that Salmonella diverged from E. coli after acquiring genes enabling systemic infection and survival in macrophages.

Ecological and Evolutionary Pressures

Host-Pathogen Interactions:

The evolutionary success of Salmonella is linked to its ability to exploit host defenses. For example, genes enabling intracellular survival have allowed it to persist within macrophages.

Environmental Reservoirs:

While primarily associated with animals, Salmonella can survive in environmental reservoirs like water and soil. This versatility has helped it spread globally.

Evolutionary Insights from Genomics

Advances in genomic sequencing have clarified Salmonella's evolutionary trajectory:

Core Genome: Highly conserved genes related to metabolism and cell structure.

Accessory Genome: Includes mobile genetic elements like plasmids, transposons, and bacteriophages that contribute to virulence and antibiotic resistance.

Molecular Clock Studies:

Analysis of mutation rates suggests that Salmonella continues to evolve rapidly, especially in response to human interventions like antibiotics.

Key Takeaways:

Salmonella evolved from a common ancestor with E. coli but adapted to systemic infections through gene acquisition and environmental pressures.

Its genomic flexibility and ability to colonize diverse hosts have been critical to its evolutionary success.

Relationships with other genera, like Escherichia and Shigella, reveal a shared evolutionary history with divergence driven by ecological specialization.

Is there much evidence of host-specificity?

Yes, there is considerable evidence of host specificity in Salmonella, with some serovars adapting to infect specific hosts more effectively than others. However, the extent of host specificity varies among Salmonella serovars and is influenced by their evolutionary adaptations and ecological niches. Here's a breakdown:

Host-Specific vs. Broad-Host-Range Serovars

Host-Specific Serovars:

These serovars are restricted to specific hosts and often cause severe, systemic infections in their target species.

Salmonella Typhi: Human-specific, causing typhoid fever.

Salmonella Paratyphi: Human-specific, causing paratyphoid fever.

Salmonella Dublin: Primarily infects cattle but can occasionally infect humans, usually causing severe disease.

Salmonella Choleraesuis: Adapted to pigs and can cause systemic infections in swine.

Broad-Host-Range Serovars:

These serovars infect a wide range of hosts and typically cause gastroenteritis.

Salmonella Enteritidis: A leading cause of foodborne illness in humans, associated with poultry and eggs but can infect other animals.

Salmonella Typhimurium: Infects a wide variety of mammals, birds, and reptiles, and is a common cause of foodborne illness.

Mechanisms of Host Specificity
The host specificity of Salmonella serovars is influenced by several genetic and molecular factors:

Pathogenicity Islands (SPIs):

Salmonella Pathogenicity Islands (SPIs) encode virulence factors like Type III Secretion Systems (T3SSs) that allow the bacteria to invade and survive in host cells.

Differences in SPI genes contribute to host specificity. For instance:

S. Typhi and S. Paratyphi have unique virulence factors (e.g., Vi antigen) that help evade the human immune system.

S. Dublin has genes that enhance its ability to persist in cattle.

Adhesins and Surface Proteins:

Host specificity is often mediated by adhesins, which enable the bacteria to bind to specific host tissues.

For example, S. Typhi expresses fimbriae and adhesins that preferentially bind to receptors found in human intestinal epithelial cells.

Immune Evasion:

Host-specific serovars have evolved mechanisms to evade or modulate the immune responses of their target hosts.

S. Typhi produces proteins that suppress human immune responses, facilitating systemic infection.

Metabolic Adaptations:

Host-specific serovars often exhibit metabolic pathways tailored to the nutrient environment of their host. For example, some serovars can utilize host-specific compounds as energy sources.

Evidence from Genomic Studies
Genomic studies have revealed key differences between host-specific and broad-host-range serovars:

Unique Genes:

Host-specific serovars often have genes not found in broad-host-range strains. These genes may encode virulence factors, metabolic enzymes, or regulatory proteins specific to their host environment.

Pseudogenes:

Host-restricted serovars like S. Typhi often have many pseudogenes—nonfunctional remnants of genes. This suggests they have lost functions unnecessary for survival in their specific host, leading to a narrowing of their ecological niche.

Phylogenetic Insights:

Phylogenetic analysis shows that host-restricted serovars tend to form distinct clades, reflecting their adaptation to specific hosts.

Experimental Evidence

Animal Models:

Studies using animal models have demonstrated the inability of host-specific serovars to infect non-native hosts effectively.

S. Typhi does not cause disease in mice or cattle without genetic modification.

S. Dublin causes systemic disease in cattle but only sporadic, severe infections in humans.

Natural Observations:

Epidemiological data show strong associations between certain serovars and specific hosts. For example:

S. gallinarum and S. pullorum are highly adapted to poultry, causing fowl typhoid and pullorum disease, respectively.

Exceptions and Spillover Events

While some Salmonella serovars are highly host-specific, spillover events can occur:

Broad-host-range serovars like S. Typhimurium can infect a wide variety of species, often leading to zoonotic transmission to humans.

Host-specific serovars can occasionally infect non-native hosts, sometimes leading to severe disease. For instance:

S. Dublin can cause life-threatening bacteremia in humans, particularly in immunocompromised individuals.

Implications for Public Health and Veterinary Medicine

Understanding host specificity is crucial for controlling Salmonella infections:

Zoonotic Risks: Broad-host-range serovars pose significant zoonotic threats, especially in foodborne outbreaks.

Vaccination and Control Strategies: Vaccines and interventions can be tailored to target specific serovars in their primary hosts (e.g., poultry vaccines against S. Enteritidis).

Conclusion
Host specificity in Salmonella reflects a complex interplay of genetic, molecular, and ecological factors. While some serovars are highly specialized, others maintain the flexibility to infect a broad range of hosts, contributing to their global prevalence and significance as pathogens.

What the UC Davis Health study, led by Professor Andreas Bäumler of the Department of Medical Microbiology and Immunology found is the subject of a paper in Proceeding of The National Academy of Science (PNAS) and a UC Davis press release by Nadine A Yehya:

New study shows how salmonella tricks gut defenses to cause infection
(SACRAMENTO) A new UC Davis Health study has uncovered how Salmonella bacteria, a major cause of food poisoning, can invade the gut even when protective bacteria are present. The research, published in the Proceedings of the National Academy of Sciences, explains how the pathogen tricks the gut environment to escape the body's natural defenses.
The digestive system is home to trillions of bacteria, many of which produce short-chain fatty acids (SCFAs) that help fight harmful pathogens. But Salmonella manages to grow and spread in the gut, even though these protective compounds are present. The study asks: How does Salmonella get around this defense?

We knew that Salmonella invades the small intestine, although it is not its primary site of replication. The colon is.

Professor Andreas Bäumler, lead author
Department of Medical Microbiology and Immunology
School of Medicine
University of California at Davis, Davis, CA, USA.

Bäumler and his team discovered that the answer lies in how the pathogen changes the gut’s nutrient balance. When Salmonella enters the small intestine, it causes inflammation in the gut lining and disrupts the normal absorption of amino acids from food. This creates an imbalance in nutrients in the gut.

The imbalance gives Salmonella the resources it needs to survive and multiply in the large intestine (colon), where beneficial bacteria usually curb its growth. The study showed that salmonella causes inflammation in the small intestine in order to derive nutrients that fuel its replication in the colon.

Salmonella alters gut nutrient environment to survive

Using a mouse model, the team looked closely at how Salmonella changed the chemical makeup of the gut. They traced amino acid absorption in the small and large intestines.

They found that in mice that were infected with Salmonella, there was less absorption of amino acids into the blood. In fact, two amino acids, lysine and ornithine, became more abundant in the gut after infection. These amino acids helped Salmonella survive by preventing the growth-inhibiting effects of SCFAs. They did this by restoring Salmonella’s acidity (pH) balance, allowing the pathogen to bypass the microbiota’s defenses.

Our findings show that Salmonella has a clever way of changing the gut’s nutrient environment to its advantage. By making it harder for the body to absorb amino acids in the ileum, Salmonella creates a more favorable environment for itself in the large intestine.

Professor Andreas Bäumler.

In the study, the team showed that Salmonella uses its own virulence factors (disease causing molecules) to activate enzymes that break down key amino acids like lysine. This helps the pathogen avoid the SCFAs’ protective effects and grow more easily in the gut.

New insights could lead to better gut infection treatments

The new insights potentially explain how the gut environment changes during inflammatory bowel disorders , such as Crohn's disease and ulcerative colitis, and could lead to better treatments for gut infections. By understanding how Salmonella changes the gut environment, researchers hope to develop new ways to protect the gut microbiota and prevent these infections.

This research uses a more holistic approach to studying gut health. It not only gives us a better understanding of how Salmonella works, but also highlights the importance of maintaining a healthy gut microbiota. Our findings could lead to new treatments that help support the microbiota during infection. By learning how a pathogen manipulates the host’s system, we can uncover ways to boost the host’s natural defenses.

Dr. Lauren Radlinski, first author.
Department of Medical Microbiology and Immunology
School of Medicine
University of California at Davis, Davis, CA, USA.

The study’s results could inspire future treatments, including probiotics or dietary plans designed to strengthen the body’s natural defenses against harmful pathogens.

Coauthors of the study are Andrew Rogers, Lalita Bechtold, Hugo Masson, Henry Nguyen, Anaïs B. Larabi, Connor Tiffany, Thaynara Parente de Carvalho and Renée Tsolis of UC Davis.

Significance
The microbiota protects the host from microorganisms that cause disease in unprotected or immunocompromised individuals. Enteric pathogens such as Salmonella enterica serovar (S.) Typhimurium are adept at circumventing and weakening these protections and in doing so render the host susceptible to infection. Here, we identify a strategy by which S. Typhimurium uses its virulence factors to manipulate the host environment in the small intestine to trigger downstream changes in the environment of the large intestine that enable the pathogen to overcome microbiota-mediated defenses. The more general implications of our work are that ileitis-induced malabsorption causes downstream changes in microbial growth conditions in the large intestine, which can trigger compositional changes.

Abstract
The gut microbiota produces high concentrations of antimicrobial short-chain fatty acids (SCFAs) that restrict the growth of invading microorganisms. The enteric pathogen Salmonella enterica serovar (S.) Typhimurium triggers inflammation in the large intestine to ultimately reduce microbiota density and bloom, but it is unclear how the pathogen gains a foothold in the homeostatic gut when SCFA-producing commensals are abundant. Here, we show that S. Typhimurium invasion of the ileal mucosa triggers malabsorption of dietary amino acids to produce downstream changes in nutrient availability in the large intestine. In gnotobiotic mice engrafted with a community of 17 human Clostridia isolates, S. Typhimurium virulence factors triggered marked changes in the cecal metabolome, including an elevated abundance of amino acids. In an ex vivo fecal culture model, we found that two of these amino acids, lysine and ornithine, countered SCFA-mediated growth inhibition by restoring S. Typhimurium pH homeostasis through the inducible amino acid decarboxylases CadA and SpeF, respectively. In a mouse model of gastrointestinal infection, S. Typhimurium CadA activity depleted dietary lysine to promote cecal ecosystem invasion in the presence of an intact microbiota. From these findings, we conclude that virulence factor–induced malabsorption of dietary amino acids in the small intestine changes the nutritional environment of the large intestine to provide S. Typhimurium with resources needed to counter growth inhibition by microbiota-derived SCFAs.

The gut microbiota is a critical frontline barrier that precludes the expansion of invading microorganisms through the production of antimicrobial compounds and the depletion of essential nutrients (1). During homeostasis, obligately anaerobic bacteria dominate the microbiota of the large intestine and ferment unabsorbed carbohydrates to produce high luminal concentrations of the short-chain fatty acids (SCFAs) acetate, propionate, and butyrate. These SCFAs are weak acids that become protonated in mildly acidic environments (HAc), such as the lumen of the colon (pH 5.7 to 6.2) (2), as the pH approaches the respective negative base-10 logarithm of the acid dissociation constant (pKa) for each molecule (~pH 4.7). Protonated SCFA are membrane permeable, but exposure to a more neutral pH in the cytosol (pH 7.2 to 7.8) (3–5) results in their dissociation into the salt and a proton (Ac⁻ + H⁺). The consequent acidification of the bacterial cytosol results in growth inhibition and serves as a canonical, nonspecific defense mechanism against invading enteric pathogens such as Salmonella enterica serovar Typhimurium (S. Typhimurium) (3, 6–8).

S. Typhimurium uses its virulence factors, two type III secretion systems (T3SS-1 and T3SS-2) (9, 10) encoded by Salmonella pathogenicity island (SPI)1 and SPI2 (11, 12), respectively, to break colonization resistance through mechanisms that are not fully resolved (13, 14). T3SS-1 and T3SS-2 trigger intestinal inflammation (15–17), which boosts growth of S. Typhimurium by increasing the availability of host-derived respiratory electron acceptors, including tetrathionate (18), nitrate (19, 20), and oxygen (21). In addition, aspartate is liberated when phagocyte-derived reactive oxygen species lyse luminal bacteria (22), which fuels growth of S. Typhimurium through fumarate respiration (23). Tetrathionate respiration has been shown to promote growth of S. Typhimurium in the lumen of the murine cecum by utilizing ethanolamine (24), which is generated when taurine liberated during deconjugation of bile acids is used as an electron acceptor by Deltaproteobacteria. Oxygen and nitrate enable the pathogen to utilize host-derived lactate (25) or 1,2-propanediol (26), a microbiota-derived fermentation product of pentoses. However, growth during in vitro culture under conditions that mimic the cecal environment suggests that high concentrations of SCFAs and the acidic environment of the cecum counter the competitive edge that oxygen and nitrate respiration confer upon the pathogen (27). These data suggest that S. Typhimurium virulence factors act on the host to generate yet unidentified resources that enable the pathogen to overcome growth inhibition by SCFAs in the lumen of the large intestine.

Here, we used untargeted metabolomics to identify resources generated by S. Typhimurium virulence factor activity during gastrointestinal infection and investigated their role in countering SCFA-mediated intracellular acidification.

L.C. Radlinski, A.W.L. Rogers, L. Bechtold, H.L.P. Masson, H. Nguyen, A.B. Larabi, C.R. Tiffany, T.P.D. Carvalho, R.M. Tsolis, A.J. Bäumler
, Salmonella virulence factors induce amino acid malabsorption in the ileum to promote ecosystem invasion of the large intestine Proc. Natl. Acad. Sci. U.S.A. (2024) 121(47), e2417232121, DOI: 10.1073/pnas.2417232121.

Copyright: © 2024 The authors.
Published by the National Academy of Science. Open access.
Reprinted under a Creative Commons Attribution 4.0 International license (CC BY 4.0)

I wonder if a creationist would be brave enough to attempt to explain these advantageous abilities of Salmonella, which enable it to survive and overcome our natural defences in our intestines in terms of 'devolution' from an initially designed perfection, or, if not, explain why, if the E.coli's flagellum is proof of their designer god, as devotees of Michael J. Behe insist, it isn't also proof of their designer god's work in Salmonella.

Alternatively, perhaps they could talk us through the process by which 'sin' is able to redesign a pathological bacterium to make it better at making us sick and increasing the suffering in the world, and even tailor-making some serovars so they target specific species, one of which is human.

Malevolent Design - How Sleeping Sickness Parasites Are 'Designed' to Evade Our Immune System

Sleeping sickness

Discovery Illuminates How Sleeping Sickness Parasite Outsmarts Immune Response | Johns Hopkins | Bloomberg School of Public Health

Trypanosoma brucei is a blood-borne eukaryote parasite that should leave believers in an intelligent designer, open-mouthed in admiration for its inventive genius. Christian fundamentalist creationists of the white supremacist persuasion should also admire the racist that, through T. brucei, has managed to keep large parts of Africa technologically under-developed due to the difficult in maintaining herds of domestic animals where the vector of these parasites - the tsetse fly - is common.

As a vector, the tsetse fly is a triumph of malevolent design which I mentioned in my popular book, The Unintelligent Designer: Refuting the Intelligent Design Hoax, but it would have been all for nothing without the nasty little T. brucei to cause sleeping sickness in humans and the debilitating disease "nagana" in cattle.

What creationist admires of the divine malevolence they believe designs these things should now be marveling at is the sheer brilliance of the design by which it manages to evade the immune system, which they believe was created by the same designer god which now regards his design as a problem to be overcome oh parasites like T. brucei can continue making Africans and their cattle sick.

Malevolent Designer News - Stand By For The Next Move In The Mpox Arms Race

Mpox virus particles

Mpox Vaccine Is Safe and Generates a Robust Antibody Response in Adolescents | NIAID: National Institute of Allergy and Infectious Diseases

As Medical science announces success in the search for a vaccine against the mpox virus currently spreading misery and suffering around the globe, we can be as sure as can be that creationism’s divine malevolence is working on a variant with an inbuilt way to evade the antibodies the vaccine produces, in just the same way it did with COVID-19 - if you believe a magic designer is behind these things, the way intelligent [sic] design creationists do.

Unintelligent Design - The Blunder That Causes Cancers

Ludwig Cancer Research

It has often been a theme of my blog posts how, if we regard cells as the result of conscious (I won't use the term 'intelligent' as that's singularly inappropriate, as we shall see) design then the picture quickly emerges of a bungling incompetent, cobbling together Heath-Robinson solutions to problems of its own incompetent making and lack of foresight.

The entire system of epigenetics, for example, is only necessary in a multicellular organism with its cell specialisation because specialised cells only need a small subset of the entire genome, yet, because cells replicate using exactly the same process that single-celled organisms use, where the entire genome needs to be replicated in every daughter cell, the cells of multicellular organisms such as humans each receive the entire species genome. So, most of it needs to be turned off.

This is where the epigenetic system comes in where methyl groups are attached to key bases in the DNA which prevents that section being transcribed into RNA, effectively switching the gene off. There are other components to the epigenetic system, but that is the pertinent component as far as this particular blunder is concerned.

The problem starts when a methyl group is attached to a cytosine base (C in the CGTA genetic code) which is next to a guanine(G) base.

Unintelligent Design Or Sheer Malevolence? - Defective Sperm Puts Mother And Baby At Risk

AI-generated graphic illustrating preeclampsia
(with AI spelling)

ChatGPT4o

Defective sperm doubles the risk of preeclampsia | Lund University

Christian superstition insists that every person conceived is a creation of their omniscient, omnipotent god who knows and has always known, exactly who is going to be born and has an oven-ready plan for their entire existence. Each baby conceived was exactly as the Christian god intended, down to the last detail of the DNA Exactly which sperm fertilizes which egg when, is part of the god's omniscient, perfect plan.

Leaving aside the absurdity of throwing millions of sperms at a single egg to produce that conception, when only a predetermined one was going to be the winner in order to produce the predetermined genome, when a single sperm would have been just as effective, we are left with the disturbing idea that any and all genetic defects were the intended outcome of that conception; the intention of a supposedly omnibenevolent god.

Now, it might, in fact it definitely is possible for a Christian to imagine some ultimate good will come from a child with a genetic defect, but what if a defect in the sperm causes harm not just to the baby, but to the mother? Are we to conclude that a mother whose life is put at risk by a defective sperm from her partner was the intended victim of an 'all-loving' god? What possible good can come from a mother's (and almost invariably her baby's) life being in danger from something beyond her control? What possible good can come from preeclampsia?

Malevolent Design - How Chlamydia Is 'Designed' to Cause Maximum Sufferring.

Schematic representation of how a C. pneumoniae cell infects a human cell. The bacterium injects the protein SemD (green) into the cell, which activates the cell protein N-WASP, which in turn initiates vesicle formation.

Credit: HHU/Fabienne Kocher.

Universität Düsseldorf: Original or copy: How Chlamydia manipulate the host cell

The problem of parasites for creationists is one that, despite the best efforts of apologists like Michael J Behe of the Deception Institute, just won't go away.

Sadly, Behe shot himself in the foot with his original claim to have proven 'intelligent [sic] design in living organisms with his choice of the bacterial flagellum in E. coli, where he persuaded his willing audience that these nasty little pathogens had been intelligently designed - and by unspoken assumption, designed by the locally-popular god.

Now creationists wave his 'proof' of design as evidence for their creator god because only their god is capable of creating living organisms.

But, with characteristic double-think, creationists also argue that their god is omnibenevolent, so something else must have created parasites like E. coli, and, courtesy again of Michael J. Behe, they cite 'Sin' causing 'genetic entropy' and the absurd idea of 'devolution' this supposedly causes, as the cause of parasites and pathogens (but not the bacterial flagellum, obviously!).

The problem with that notion is that they need to do their double-think trick one more time and believe that a trait with improves a pathogens ability to live and reproduce in its host makes it somehow less perfect that one without that trait. So, in the creationist's world, an improvement is a move away from perfection!

But, with a cult that appears to believe learning is a move away from the 'perfection' of pristine ignorance (from whence comes expertise in all aspects of science), that's probably not too difficult a feat of mental gymnastics for a creationist to perform.

Refuting Creationism - Even More Signs of The Divine Malevolence's Obsessive Compulsive Disorder?

Over 160,000 new virus species discovered by AI - The University of Sydney

This is the second paper today to show the apparent obsession creationism's putative designer has with creating viruses, if you believe that superstition.

The first paper dealt with the discovery that there are some 600 different viruses to be found on a used toothbrush and on the shower heads in US bathrooms; this one reports on a discovery that makes that finding pale into insignificance. It is the discovery, using the machine learning of AI, of 161,979 new viruses!

This is just tip of the iceberg as the authors say the method just scratches the surface of biodiversity and opens up a world of discovery with millions more to be discovered.

Structural model at atomic resolution of bacteriophage T4

By Dr. Victor Padilla-Sanchez, PhD https://www.drvictorpadillasanchez.com
Own work, CC BY-SA 4.0, Link

Viruses are teeming on your toothbrush, showerhead - Northwestern Now

Creationism's putative creator is nothing if not obsessive.

One of its obsessions appears to be designing ever-more exquisite ways to kill its creation as almost nothing in nature exists that doesn't have something that lives on or in it, often killing it in the process or at least weakening it in some way.

Its most visible obsession seems to be with designing beetles of which there are some 500,000 species with more being discovered almost daily. It's highly likely that there may be as many as a million different beetles in the world, many of which catch and devour other arthropods.

But it's in the field of virology that we find another obsession with designing variations on a general theme. Not only are there literally hundreds of thousands of viruses but every species has multiple variants - look at the number of different variants of the SARS-CoV-2 virus that have emerged since the initial wave of the COVID-19 pandemic!

Malevolent Design - How The Black Widow Spider's Toxins Harm Us Mammals

Latrodectus hesperus female with egg sac.

Scientists decode black widow spider venom

Black widow spiders have a cocktail of toxins, most of which are effective against their arthropod prey such as insects, but one of them, α-latrotoxin, is very effective against vertebrates, including humans, although even the smallest vertebrates don't normally feature in the black widow's diet.

So why did this toxin evolve?

Normally, a species which is capable of delivering a nasty, even lethal, bite to a threat, rather than to prey, evolves strategies for avoiding doing so, while warning that it could if it wanted to - rather like a creationists avoiding answering a question while pretending they could if they wanted to, only without the pretense. Most species do this with warning colours or, in the case of the rattlesnake, a warning rattle. This is because using venom against a threat might mean there isn't enough left if the next potential meal wanders by, so it's better to warn and threaten than to actually bite.

But not so the black widow, except for the strikingly marked European species, Latrodectus tredecimguttatus, and the South American, Latrodectus curacaviensis. If anything, the black widow is cryptocamoflaged to not be noticed in the dark places they inhabit.

Unintelligent Designe - Creationism's Blundering Heath-Robinson 'Designer' Strikes Again - And Causes Cancer

Intelligently designed apparatus for teaching mountaineers.

William Heath-Robinson

How Cells Recognize and Repair DNA Damage -

One thing you can depend on with creationism's putative designer is that there will never be a simple solution when there is a more complicated way to solve the problem it just created, and just like William Heath-Robinson, it will try to use pre-existing structures that were designed for an entirely different function, like a pile of books under the legs of a ladder to make it tall enough, and every piece of string holding things together will have knots in it.

And when we look beneath the superficial resemblance of design in, for example, a living cell, we find all manner of if-it-works-it'll-do solutions to problems, like the solution to the problem of breaking DNA that a team of scientists, led by Kaspar Burger, from Julius-Maximilians-Universität Würzburg (JMU) in Bavaria, Germany, have discovered.

The problem arises of course because the method for replicating DNA as cells divide is poorly designed and unnecessarily complicated in the first place. If the putative designer had devised a more sensible method for replicating cells in multicellular organisms than that used for replicating single cells where the whole genome needs to be replicated, many of the problems of erroneous copying wouldn't arise because only a small subset of the genome is needed for specialised cells.

Malevolent Design - What Creationism's Divine Malevolence Chose Not To Give Us But Lets Us To Suffer Instead

African killifish, Nothobranchius furzeri

Stowers scientists uncover a… | Stowers Institute for Medical Research

"God never restore an amputated limb". This fact, better than anything, illustrates either the limit of the power of prayer and 'faith healing' or the limit of power of the god being prayed to. There are no authenticated examples of a restored limb or of the spontaneous healing of a transected spinal cord, despite the steady supply of victims seeking a cure to 'miracle' site such as Lourdes, and the fervent prayers of victims and the families. (We can dismiss the 'Miracle of Calanda' as far too transparent a hoax to be taken seriously.) It just never happens!

An omniscience, omnipotent, omnibenevolent designer would work to minimise the suffering in its creation. To do otherwise tells us that the alleged creator is:

Unaware of it, in which case it is not omniscient.
Aware of it but powerless to prevent it, in which case it is not omnipotent.
Aware of it but indifferent to it, in which case it is not omnibenevolent.

This paradox, known as Epicurus paradox, has never been successfully answered by theists other than by hand-waving dismissals and mumblings about 'inscrutability' and 'divine plans which are not given to mankind to understand'. IOW, their god is omniscient, omnipotent and omnibenevolent even though it doesn't always behave that way and the results of its actions or inaction tell us otherwise.

The facts are not permitted to overrule the sacred dogma - which is creationism in a nutshell.

If you believe in the creationist notion of magic creation, where every species was designed according to some perfect plan, then the fact that some species lack abilities with which other species have, and with which clearly the putative designer knew how to provide, should raise some questions about why the designer made the choice not to provide them.

And if, as most self-centered fundamentalist believe, humans were at the apex of this creator god's design, then it should have the best of everything, and yet there are a myriad of examples of other species being better than humans. (See the AI panel for examples):

Many species have abilities which would be beneficial to humans if we too possessed them* Do you have a list of examples of this? Yes! Many species have evolved unique traits that, if humans possessed them, could greatly enhance our abilities or solve certain challenges. Here's a list of some remarkable examples:

Regeneration (Axolotl, Starfish)

Benefit: The ability to regrow limbs or even vital organs.
Species Example: Axolotls and starfish can regenerate entire body parts. This could help humans recover from amputations, spinal cord injuries, or organ damage.

Echolocation (Bats, Dolphins)

Benefit: Enhanced navigation and perception in low-visibility conditions.
Species Example: Bats and dolphins use echolocation to navigate in darkness or murky waters. This would allow humans to navigate dangerous environments or see without light.

Photosynthesis (Plants, Algae)

Benefit: The ability to convert sunlight directly into energy.
Species Example: Plants and algae can photosynthesize, which could eliminate the need for food in some situations, reducing hunger and energy concerns.

Extreme Durability (Tardigrades)

Benefit: Surviving extreme environments such as radiation, freezing temperatures, dehydration, and even space.
Species Example: Tardigrades (water bears) can endure near-death conditions. This would make humans far more resistant to extreme climates or space travel.

Camouflage (Chameleons, Cuttlefish)

Benefit: Blending into environments for protection or hunting.
Species Example: Chameleons and cuttlefish can change color and texture. Humans with this ability could avoid detection in dangerous situations or during combat.

Electricity Generation (Electric Eel)

Benefit: Generating electrical energy for self-defense or powering devices.
Species Example: Electric eels produce electric shocks. This could allow humans to power small devices or defend against threats using natural electricity.

Hyper-Speed Healing (Deer Antlers, Certain Lizards)

Benefit: Rapid recovery from wounds and injuries.
Species Example: Deer regrow antlers each year at an incredibly fast rate. Some lizards regrow tails. Enhanced human healing could lead to faster recovery after surgeries or injuries.

UV Vision (Birds, Insects)

Benefit: Seeing ultraviolet light to detect environmental changes or patterns invisible to the human eye.
Species Example: Many birds and insects can see ultraviolet light, which helps them find food and mates. Humans with this ability could have enhanced perception of their surroundings.

Extreme Longevity (Greenland Shark, Tortoises)

Benefit: Significantly extended lifespan.
Species Example: The Greenland shark can live for centuries, and tortoises often live over 100 years. If humans possessed this trait, we could extend lifespans, allowing more time for knowledge acquisition and creativity.

Poison Resistance (Mongoose)

Benefit: Immunity to toxins and venoms.
Species Example: The mongoose is resistant to snake venom, allowing it to hunt poisonous snakes. This could protect humans from dangerous toxins or make certain medical treatments less risky.

Hibernation (Bears, Ground Squirrels)

Benefit: Surviving long periods without food and conserving energy.
Species Example: Bears and ground squirrels hibernate during the winter. Humans with this ability could endure long periods without food, which would be useful in survival situations or space travel.

Rapid Adaptation to High Altitudes (Bar-Headed Geese)

Benefit: Increased oxygen efficiency in high-altitude or low-oxygen environments.
Species Example: Bar-headed geese can fly over the Himalayas at altitudes that would be deadly to most animals. This would allow humans to thrive in high-altitude environments or survive with less oxygen.

Flight (Birds, Bats)

Benefit: Self-powered aerial travel.
Species Example: Birds and bats have evolved to fly, which could enable humans to travel independently through the air, revolutionizing transportation and exploration.

Magnetic Field Detection (Migratory Birds, Turtles)

Benefit: Natural GPS and navigation using Earth’s magnetic fields.
Species Example: Some birds and turtles can detect the Earth’s magnetic field for navigation during migration. Humans could use this ability for more accurate navigation without technology.

Temperature Regulation (Camels, Arctic Foxes)

Benefit: Surviving extreme heat or cold without external aid.
Species Example: Camels can endure extreme desert heat, and arctic foxes thrive in freezing conditions. Humans with this ability could survive in more hostile climates with ease.

These abilities, if adapted for human use, could offer enormous benefits in fields ranging from medicine and survival to transportation and energy efficiency.

It's in the area of rapid repair and regeneration that research is being concentrated in order to gain a scientific understanding of the processes involved and particularly why they have been lost. One recent example was the discovery that zebra fish can not only repair a transected spinal cord but can regenerate a missing section of their spinal cord and restore it to full functionality.

And now we have another piece of research into how the African killifish can regenerate a missing section of fin, and in particular how the process restores just the missing tissues, no more and no less. This research from the Stowers Institute for Medical Research has just been published, open access, in the Cell Press journal iScience and announced in a Stowers Institute press release:

Stowers scientists uncover a critical component that helps killifish regenerate their fins
The findings are a step toward closing the gap on how we could one day deploy regenerative medicine in humans
Spontaneous injuries like the loss of a limb or damage to the spinal cord are impossible for humans to repair. Yet, some animals have an extraordinary capacity to regenerate after injury, a response that requires a precise sequence of cellular events. Now, new research from the Stowers Institute for Medical Research has unveiled a critical timing factor—specifically how long cells actively respond to injury—involved in regulating regeneration.

A recent study published in iScience on September 20, 2024, sought to understand exactly how an organism knows how much tissue has been lost post-injury. Led by former Predoctoral Researcher Augusto Ortega Granillo, Ph.D., in the lab of Stowers President and Chief Scientific Officer Alejandro Sánchez Alvarado, Ph.D., the team investigated how African killifish properly regrow their tail fin following damage. By analyzing tissue dynamics during regrowth, they found that in addition to known factors, including how many cells are participating and where they are located, the length of time cells spend engaged in the repair process is also key.

African killifish, Nothobranchius furzeri

One of the greatest unsolved mysteries of regeneration is how an organism knows what has been lost after injury. Essentially, the study points to a new variable in the equation of regeneration. If we can modulate the rate and the length of time that a tissue can launch a regenerative response, this could help us devise therapies that may activate and perhaps prolong the regenerative response of tissues that normally would not do so.

Dr. Alejandro Sánchez Alvarado, senior author.
Stowers Institute for Medical Research,
Kansas City, MO, USA.

Shortly after a killifish tail injury, the remaining tissue needs to know how much damage has occurred. Then, this tissue must enlist the right number of repair cells to the site of injury for the right amount of time. Damage sensing, repair cell recruitment, and timing somehow must work together to regrow the tail.
If an animal that can regenerate extremities, like a tail, loses just a tiny portion, how does it know not to regenerate a whole new tail but just the missing piece?

Dr. Alejandro Sánchez Alvarado.

To address this question, the team probed different locations of injury in the killifish tail fin.

Tail fin regeneration at 6 hours after injury. Fluorescence microscopy image shows skin cells (magenta), actively dividing cells (cyan), and transiently activated skin cell states (yellow).

They found that skin cells both near an injury and in distant, uninjured regions launch a genetic program that primes the whole animal to prepare for a repair response. Then, skin cells at the site of injury sustain this response and temporarily change their state to modify the surrounding material called the extracellular matrix. Ortega Granillo likens this matrix to a sponge that absorbs secreted signals from the injured tissue that then guides repair cells to get to work. If the signals are not received or not interpreted correctly, the regeneration process may not restore the tail’s original shape and size.

We very clearly defined when and where—at 24 hours post-injury and in the extracellular matrix—the transient cell state is acting in the fin tissue. Knowing when and where to look allowed us to make genetic disruptions and gain a better understanding of the function of these cell states during regeneration.

Augusto Ortega Granillo, first author
Stowers Institute for Medical Research,
Kansas City, MO, USA.

To investigate whether these distinct cellular states communicate information to the extracellular matrix—the supportive structure surrounding cells—during the repair process, the researchers employed the CRISPR-Cas9 gene editing technique. They specifically targeted a gene known to modify the extracellular matrix, as they had observed its activation at the onset of the regeneration response. By disrupting the function of this gene, the team aimed to determine its role in relaying information from cells to the matrix during regeneration.

These modified animals no longer know how much tissue was lost. They still regenerated, but the speed of tissue growth was deficient. This is telling us that by changing the extracellular space, skin cells inform the tissue how much was lost and how fast it should grow.

Augusto Ortega Granillo.

Tail fin regeneration at 7 days post-injury. Fluorescence microscopy image shows skin cells (magenta), actively dividing cells (cyan), and transiently activated skin cell states (yellow), where these cell states are localized now only in the very tip of the fin.
Indeed, the speed and amount of tissue regenerated in these genetically modified killifish increased regardless of whether the tail injury was mild or severe. This finding opens the possibility that cell states that modify the matrix increase regenerative regrowth. If the cell states could be adjusted, it may be a way to stimulate a more robust regeneration response.

From an evolutionary perspective, understanding why certain organisms excel at regeneration while others, such as humans, have limited regenerative abilities is a driving force in the field of regenerative biology. By identifying general principles in organisms with high regenerative capacity, researchers aim to potentially apply these insights to enhance regeneration in humans. This comparative approach not only sheds light on the evolutionary aspects of regeneration but also holds promise for developing novel therapeutic strategies in regenerative medicine.

Our goal is to understand how to shape and grow tissues. For people who sustain injuries or organ failure, regenerative therapies could restore function that was compromised during illness or following injury.

Augusto Ortega Granillo.

Post-injury fin growth shown over time in the African killifish.
via GIPHY

Additional authors include Daniel Zamora, Robert Schnittker, Allison Scott, Alessia Spluga, Jonathon Russell, Carolyn Brewster, Eric Ross, Daniel Acheampong, Ning Zhang, Ph.D., Kevin Ferro, Ph.D., Jason Morrison, Boris Rubinstein, Ph.D., Anoja Perera, and Wei Wang, Ph.D.

Highlights

Amputation position changes tissue-wide proliferation response
Regeneration deploys transient regeneration-activated cell states.
Sqstm1 slows down regenerative outgrowth in distal injuries.
Prediction: positional information is transduced by ECM changes during regeneration.

Summary
Injury is common in the life of organisms. Because the extent of damage cannot be predicted, injured organisms must determine how much tissue needs to be restored. Although it is known that amputation position affects the regeneration speed of appendages, mechanisms conveying positional information remain unclear. We investigated tissue dynamics in regenerating caudal fins of the African killifish (Nothobranchius furzeri) and found position-specific, differential spatial distribution modulation, persistence, and magnitude of proliferation. Single-cell RNA sequencing revealed a transient regeneration-activated cell state (TRACS) in the basal epidermis that is amplified to match a given amputation position and expresses components and modifiers of the extracellular matrix (ECM). Notably, CRISPR-Cas9-mediated deletion of the ECM modifier sequestosome 1 (sqstm1) increased the regenerative capacity of distal injuries, suggesting that regeneration growth rate can be uncoupled from amputation position. We propose that basal epidermis TRACS transduce positional information to the regenerating blastema by remodeling the ECM.

Graphical abstract

Introduction
For many organisms, including humans, the preservation of anatomical form and function depends in great part on the periodic elimination and restoration of cells. This process is referred to as tissue homeostasis. In mammals, the rate of tissue homeostasis varies widely across organs; i.e., self-renewal of the intestinal and lung epithelia has been estimated to take 5 days and up to 6 months, respectively.^1,2 As such, specific mechanisms exist in adult tissues responsible for sustaining specific rates of tissue homeostasis to mitigate normal, physiological wear and tear. The intricate balance of tissue homeostasis can be severely disrupted by injury. During their lifespans, all multicellular organisms are likely to experience some kind of injury. Unlike physiologically regulated tissue homeostasis, injuries and the extent of the damage incurred are unpredictable. This creates a challenge for organisms to monitor and deploy an anatomically specific regeneration response proportional to the magnitude of the injury.

During regeneration, a specialized structure known as blastema forms through the rapid proliferation and subsequent differentiation of multiple cell types to restore the missing tissue.³ For instance, it has been shown that osteoblast differentiation is accelerated in regenerating fins. Newly differentiated osteoblasts appear 4 days earlier in regenerated tissue compared to the pre-existing tissue, also referred to as the stump.⁴ It is not known whether there is a regeneration-specific osteoblast differentiation program or if differentiation trajectories used during tissue homeostasis can be accelerated during regeneration. Regeneration has also been shown to alter rates of tissue growth. In vertebrates, the speed of regeneration differs when different amounts of tissue are lost.⁵ For example, fish caudal fin amputations close to the base of the appendage, a proximal amputation, display higher growth rates than amputations performed further away from the base of the fin, a distal amputation.^6,7

To date, it is not known how injured tissues detect amputation position and what processes may encode positional information during regeneration. Efforts to identify deposited positional information prior to injury led to the identification of transcripts and proteins that are differentially expressed along the proximo/distal (P/D) axis in the intact zebrafish fin.⁸ However, these differences are lost during regeneration, leading to the hypothesis that positional information must be redefined during regeneration.⁸ Alternatively, it has been proposed that migratory progenitor cells retain positional identity from their locations prior to injury. This opens up the possibility that progenitors communicate positional information to the new tissue to determine regeneration growth rate.^9,10 But the mechanism of positional information retention and potential relay to other cells has not yet been identified.

Furthermore, it has been suggested that positional information is encoded in the tissue within the thickness of the bone at the plane of amputation^11,12 and that mechanical distension of the epidermis during wound closure constitutes a direct measurement of the amputation position by the wound epidermis. A wave of mechanical distension in the basal epidermis was shown to propagate to different lengths according to the amputation position.¹³ To add to the complexity of this process, it was shown that there is a 2-day time window at the beginning of regeneration when positional information is possibly reestablished de novo. If blastemas are impaired in their proliferative ability during this time window, the wrong positional information is encoded in the regenerated appendage, so multiple rounds of regeneration consistently grow abnormal tissue sizes in the absence of any further impairment of proliferation.¹⁴ It is conceivable that independent mechanisms of positional information coordinating the regenerative response exist. There may be redundant and complementary means to adequately relay and deposit positional information into the new tissue. This would ensure that form and function are restored following diverse and unpredictable injury.

Here, we deploy spatial and temporal analysis of proliferation and single-cell transcriptomic profiling to measure molecular and cellular changes along the caudal fin P/D axis. We chose the African killifish Nothobranchius furzeri for our studies because of the reduced complexity of differential gene expression and gene regulation compared to the more broadly utilized zebrafish.¹⁵ We show that amputation position influences the length of time (persistence) it takes for tissues to progress through regeneration. We report on the discovery of a basal epidermal subpopulation that shows a transient regeneration-activated cell state (TRACS) likely to participate in mediating positional information in the regenerating blastema. Altogether, our study demonstrates that amputations along the P/D axis result in defined spatial and temporal rates of proliferation. We propose that such dynamics likely initiate the proportional changes in tissue architecture that may ultimately define the scale and rate of regeneration of amputated tissues.

It's worth repeating what the Sowers Institute news release said at this point:

From an evolutionary perspective, understanding why certain organisms excel at regeneration while others, such as humans, have limited regenerative abilities is a driving force in the field of regenerative biology.

No doubts there then on the part of the authors that the facts can't be explained by evolution and are better explained by creationism's childish superstition, and of course the Theory of Evolution explains it fully without the need to explain why something which evolved for one species or from a common ancestor is retained by one line but not another in terms of the intention, malevolent, benign or indifferent, of the mindless, directionless natural process that drives it.

Creationism, on the other hand, has to try to reconcile the reality with what they believe about their putative designer, which includes explaining why, if it isn't malevolent, it designs organisms to look as though a malevolent designer designed them.

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Rosa Rubicondior

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