A hallmark of positive‐sense RNA viruses is the formation of membranous shelters for safe replication in the cytoplasm. Once considered invisible to the immune system, these viral shelters are now found to be antagonized through the cooperation of autophagy proteins and anti‐microbial GTPases. This coordinated effort of autophagy proteins guiding GTPases functions against not only the shelters of viruses but also cytoplasmic vacuoles containing bacteria or protozoa, suggesting a broad immune‐defense mechanism against disparate vacuolar pathogens. Fundamental questions regarding this (...) process remain: how the host recognizes these membranous structures as a target, how the autophagy proteins bring the GTPases to the shelters, and how the recruited GTPases disrupt these shelters. In this review, these questions are discussed, the answers to which will significantly advance our understanding of the response to vacuole‐like structures of pathogens, thereby paving the way for the development of broadly effective anti‐microbial strategies for public health. (shrink)

Toxoplasma gondii is a highly successful parasite capable of infecting virtually all warm-blooded animals by actively invading nucleated host cells and forming a modified compartment where it replicates within the cytosol. The parasite-containing vacuole provides a safe haven, even in professional phagocytes such as macrophages, which normally destroy foreign microbes. In an effort to eliminate the parasite, the host up-regulates a family of immunity-related p47 GTPases (IRGs), which are recruited to the parasite-containing vacuole, resulting in membrane rupture and digestion of (...) the parasite. To avoid this fate, highly virulent strains of Toxoplasma coat the external surface of their vacuole with a secretory serine/threonine kinase, known as ROP18. At this host-pathogen interface, ROP18 phosphorylates and inactivates IRGs, thereby protecting the parasite from killing. These findings reveal a novel molecular mechanism by which the parasite disarms host innate immunity. (shrink)

Intracellular NLR (Nucleotide‐binding domain and Leucine‐rich Repeat‐containing) receptors are sensitive monitors that detect pathogen invasion of both plant and animal cells. NLRs confer recognition of diverse molecules associated with pathogen invasion. NLRs must exhibit strict intramolecular controls to avoid harmful ectopic activation in the absence of pathogens. Recent discoveries have elucidated the assembly and structure of oligomeric NLR signalling complexes in animals, and provided insights into how these complexes act as scaffolds for signal transduction. In plants, recent advances have provided (...) novel insights into signalling‐competent NLRs, and into the myriad strategies that diverse plant NLRs use to recognise pathogens. Here, we review recent insights into the NLR biology of both animals and plants. By assessing commonalities and differences between kingdoms, we are able to develop a more complete understanding of NLR function. (shrink)

The behavioral immune system (BIS) includes perceptual mechanisms for detecting cues of contamination. Former studies have indicated that moisture has a disgusting property. Therefore, moisture could be a target for detecting contamination cues by the BIS. We conducted two experiments to examine the psychophysical basis of moisture perception and clarify the relationship between the perception of moisture and the BIS. We assumed that the number of high luminance areas in a visual image provided optical information that would enable the visual (...) perception of moisture. In two experiments, we presented eight images of dough that contained different amounts of moisture as experimental stimuli. The amount of moisture shown in the images was increased in eight steps, from 28.6% to 42.9% of the total weight of the dough. In Experiment 1, the images were randomly presented on a computer display, and the participants (n = 22) were asked to rank the images in the order of the visually perceived moisture content. In Experiment 2, the participants (n = 15) completed pairwise comparisons based on the perceived moistness of the images. Furthermore, to examine the BIS responses, the participants rated the strength of disgust evoked by the stimuli, their motivation to avoid touching the stimuli, and the estimated magnitude of the risk of contamination by physical contact with the stimuli. The results indicated that the moisture content and the numbers of high luminance areas in the images accurately predicted the perception of moisture, suggesting that the detection of visual moisture was highly accurate, and the optical information served as an essential perceptual cue for detecting moisture. On the other hand, the BIS responses peaked in response to stimuli having approximately 33% to 39% moisture content. These results show that objects containing a moderate amount of moisture could be the target of visually detecting pathogens by the BIS. (shrink)

The secretory system of plant cells sorts a large number of soluble proteins that either are secreted or accumulate in vacuoles. Secretion is a bulk‐flow process that requires no information beyond the presence of a signal peptide necessary to enter the endoplasmic reticulum. Many vacuolar proteins are glycoproteins and the glycans are often modified as the proteins pass through the Golgi complex. Vacuolar targeting information is not contained in glycans as it is in animal cells; rather, targeting information is (...) in polypeptide domains as it is in yeast cells. Several such domains have now been identified, but these show little or no amino acid sequence homology. We discuss the possibilities that targeting of protein to plant vacuoles may involve receptors as well as aggregation of protein at low pH. (shrink)

Scrapie and Creutzfeldt–Jakob disease (CJD) are caused by prions, which appear to be different from both viruses and viroids. Prions contain protein which is required for infectivity, but no nucleic acid has been found within them. Prion proteins are encoded by a cellular gene and not by a nucleic acid within the infectious prion particle. A cellular homologue of the prion protein has been IDentified. The role of this homologue in metabolism is unknown. Prion proteins, but not the cellular homologue, (...) aggregate into rod‐shaped particles that are histo‐chemically and ultrastructurally IDentical to amyloid. Extracellular collections of prion proteins form amyloid plaques in scrapie‐ and CJD‐infected rodent brains as well as CJD‐infected human brains. Within the plaques, prion proteins assemble to form amyloid filaments. Elucidating the molecular differences between the prion protein and its cellular homologue may be important in understanding the chemical structure and replication of prions. (shrink)

Theoretical substantiations and practical recommendations on media educational contain against gender stereotypes in the Ukrainian mass media are given in the work. Attention is paid to the pathogenic factor of the use of gender-sensitive content. The work is based on propedeutic theoretic studies of cultural and psychosocial background of Ukraine. We also used a content analysis of news and advertising materials of heterogenic media; sociologic methods ; modelling of educational situations and forecasting of expected results. That was an end-to-end method (...) of generalization that covered theoretical and practical stages of the study. It is proved that despite the weakening of gender divisions in the socio-cultural sphere in the world, in developing countries gender stereotypes remain a powerful tool for affective approach of media and advertising to the consumer. Author's ways to increase the level of media literacy and critical thinking with the help of gender-sensitive experiments, mini-projects, filling the media space with "mirror" about sexist content and creating a personal media field are proposed. (shrink)

It has long been believed that membrane proteins present in degradative compartments such as endolysosomes or vacuoles would be destined for destruction. Now however, it appears that mechanisms and machinery exist in simple eukaryotes such as yeast and more complex organisms such as mammals that can rescue potentially “doomed” membrane proteins by retrieving them from these “late” compartments and recycling them back to the Golgi complex. In yeast, a sorting nexin dimer containing Snx4p can recognize and retrieve the Atg27p (...) membrane protein while in mammals, the AP5 complex (with SPG11 and SPG15) directs the recycling of Golgi‐localized proteins along with the cation‐independent mannose 6‐phosphate receptor (CIMPR). Although the respective machinery is different, there is much commonality between yeast and mammals regarding the mechanisms of retrieval and the physiological importance of these late recycling pathways. (shrink)

Among pathogenic micro‐organisms that evade the mammalian immune responses, Trypanosoma brucei has developed the most elaborate capacity for antigenic variation. Trypanosomes branched early during eukaryotic evolution. They are characterized by many aberrations, ranging from the unusual compartmentation of metabolic pathways to the heresy of RNA editing. The ubiquitous phenomenon of glycosylphosphatidylinositol‐anchoring of eukaryotic plasma membrane proteins and RNA trans‐splicing (trypanosome genes contain no introns), which adds an identical leader sequence to all trypanosome mRNAs, were first defined during studies of antigenic (...) variation. Genetic transformation of trypanosomes and the high efficiency of gene targeting provide new opportunities to investigate the regulation of antigenic variation. There is every reason to expect trypanosomes to provide further surprises and insights into the evolution of genetic regulatory mechanisms. (shrink)

Many bacteria that cause disease have the capacity to enter into and live within eukaryotic cells such as epithelial cells and macrophages. The mechanisms used by these organisms to achieve and maintain this intracellular lifestyle vary considerably, but most mechanisms involve subversion and exploitation of host cell functions. Entry into non‐phagocytic cells involves triggering host signal transduction mechanisms to induce rearrangement of the host cytoskeleton, thereby facilitating bacterial uptake. Once inside the host cell, intracellular pathogens either remain within membrane bound (...) inclusions or escape to the cytoplasm. Those living in the cytoplasm can further pirate the host actin system, using actin as a mechanism to facilitate movement within and between host cells. Organisms remaining within the vacuole have specialized mechanisms for intracellular survival and growth which involve additional communication with the host cell. Some of the processes involved in the various steps of facultative intracellular parasitism are discussed in the context of subverting the host cell cytoskeleton and signal transduction pathways for bacterial benefit. (shrink)

Phosphoinositides are inositol‐containing phospholipids whose hydrolysis is a key step in the rapid responses of animal cells to extracellular signals. Whether they play similar roles in plant cells has not been established, and some have suggested alternative roles as direct modulators of specific proteins. Nonetheless, evidence is accumulating that phosphoinositide hydrolysis mediates transduction of some signal in plants. The evidence is strongest for a role in triggering the shedding of flagella by the unicellular alga Chlamydomonas reinhardtii under acid stress. Rapid (...) kinetic analysis indicates that phosphoinositide hydrolysis occures within half a second and could trigger the rapid loss of flagella. Plant responses to pathogens and osmotic stress, as well as the regulation of turgor changes which underlie stomatal opening and closing and the movement of leaves and flower parts, may also be mediated by phosphoinositide hydrolysis. The evidence thus indicates that at least one reason plants have phosphoinositides is to mediate transduction of environmental signals. (shrink)

We have synthesized a 582,970-base pair Mycoplasma genitalium genome. This synthetic genome, named M. genitalium JCVI-1.0, contains all the genes of wild-type M. genitalium G37 except MG408, which was disrupted by an antibiotic marker to block pathogenicity and to allow for selection. To identify the genome as synthetic, we inserted "watermarks" at intergenic sites known to tolerate transposon insertions. Overlapping "cassettes" of 5 to 7 kilobases (kb), assembled from chemically synthesized oligonucleotides, were joined by in vitro recombination to produce intermediate (...) assemblies of approximately 24 kb, 72 kb ("1/8 genome"), and 144 kb ("1/4 genome"), which were all cloned as bacterial artificial chromosomes in Escherichia coli. Most of these intermediate clones were sequenced, and clones of all four 1/4 genomes with the correct sequence were identified. The complete synthetic genome was assembled by transformation-associated recombination cloning in the yeast Saccharomyces cerevisiae, then isolated and sequenced. A clone with the correct sequence was identified. The methods described here will be generally useful for constructing large DNA molecules from chemically synthesized pieces and also from combinations of natural and synthetic DNA segments. 10.1126/science.1151721. (shrink)

From a scientific standpoint, the world is more prepared than ever to respond to infectious disease outbreaks; paradoxically, globalization and air travel, antimicrobial resistance, the threat of bioterrorism, and newly emerging pathogens driven by ecological, socioeconomic, and environmental factors, have increased the risk of global epidemics.1,2,3 Following the 2002–2003 severe acute respiratory syndrome (SARS), global efforts to build global emergency response capabilities to contain infectious disease outbreaks were put in place.4,5,6 But the recent H1N1, Ebola, and Zika global epidemics have (...) shown unnecessary delays and insufficient coordination in response efforts.7,8,9,10 In a thoughtful and compelling essay,11 Thana C. de Campos argues that greater clarity in the definition of pandemics would probably result in more timely effective emergency responses, and pandemic preparedness. In her view, a central problem is that the definition of pandemics is based solely on disease transmission across several countries, and not on spread and severity together, which conflates two very different situations: emergency and nonemergency disease outbreaks. A greater emphasis on severity, such that pandemics are defined as severe and rapidly spreading infectious disease outbreaks, would make them “true global health emergencies,” allowing for priority resource allocation and effective collective actions in emergency response efforts. Sympathetic to the position taken by de Campos, here I highlight some of the challenges in the definition of severity during an infectious disease outbreak. (shrink)

Lack of vaccine confidence can contribute to drops in vaccination coverage and subsequent outbreaks of diseases like measles and polio. Low trust in vaccines is attributed to a combination of factors, including lack of understanding, vaccine scares, flawed policies, social media and mistrust of vaccine manufacturers, scientists and decision-makers. The COVID-19 crisis has laid bare societies’ vulnerability to new pathogens and the critical role of vaccines in containing this and future pandemics. It has also put science at the forefront of (...) the response, with several governments relying on academics to help shape policy and communicate with the public. Against this backdrop, protecting public trust in scientists and scientific output is arguably more important than ever. Yet, conflicts of interest in biomedical research remain ubiquitous and harmful, and measures to curb them have had limited success. There is also evidence of bias in industry-sponsored vaccine studies and academics are voicing concerns about the risks of working in a CoI prevalent research area. Here, we set out to challenge established thinking with regard to vaccine confidence, by shifting the gaze from a deficit in public understanding towards probity in research relationships and suggesting an alternative and perhaps complementary strategy for addressing vaccine mistrust. We argue that a concerted effort needs to be made to revisit the norms that undergird contemporary vaccine research, coupled with a willingness of all stakeholders to reimagine those relationships with an emphasis on demonstrating trustworthiness and probity. (shrink)

The majority of human, animal and plant viral pathogens possess genomes composed of RNA. The strategies evolved for expression and replication of viral RNA genomes can differ significantly from those utilized for expression and replication of host‐cell genetic material. Consequently, knowledge of the molecular details of these strategies can lead to a clearer understanding of the origin, evolution and control of viral pathogens. We describe recent progress in identifying important structural and functional domains of the RNA genomes and associated replicative (...) enzymes for two very different viruses: vesicular stomatitis virus, which possesses a single‐stranded RNA genome of negative polarity, and wound tumor virus, which contains a genome composed of 12 discrete segments of double‐stranded RNA. (shrink)

Graphical AbstractTesting for respiratory viruses and SARS-CoV-2 in clinical and epidemiological settings has contrasting purposes and utility. Symptomatic patients are best tested with respiratory virus panels to establish the pathogen and guide personalized treatment. Asymptomatic patients are tested for a single infectious pathogen to establish carrier status and guide containment.

The debate over recombinant DNA research is a unique event, perhaps a turning point, in the history of science. For the first time in modern history there has been widespread public discussion about whether and how a promising though potentially dangerous line of research shall be pursued. At root the debate is a moral debate and, like most such debates, requires proper assessment of the facts at crucial stages in the argument. A good deal of the controversy over recombinant DNA (...) research arises because some of the facts simply are not yet known. There are many empirical questions we would like to have answered before coming to a decision-questions about the reliability of proposed containment facilities, about the viability of enfeebled strains of E. coli, about the ways in which pathogenic organisms do their unwelcome work, and much more. But all decisions cannot wait until the facts are available; some must be made now. It is to be expected that people with different hunches about what the facts will turn out to be will urge different decisions on how recombinant DNA research should be regulated. However, differing expectations about the facts have not been the only fuel for controversy. A significant part of the current debate can be traced to differences over moral principles. Also, unfortunately, there has been much unnecessary debate generated by careless moral reasoning and a failure to attend to the logical structure of some of the moral arguments that have been advanced. (shrink)

While the unprecedented lockdown measures were at the heart of the debate in the first year of the pandemic, the focus since then has shifted to vaccination issues. The reason, of course, is that vaccines and vaccinations have become available by now. All experts agree: If mankind had failed to develop vaccines against SARS-CoV-2, the death toll would have been much higher. This issue seeks to explore what could be described as a “generational approach to vaccinations”. The question “What can (...) we do to avoid future pandemics?” is related to different aspects of the failures and successes of humanity’s vaccination strategy against SARS-CoV-2. Pathogens are among the existential risks to humanity that could potentially kill a large part of it in a very short time. For all the tragedy and horror it has brought upon the world, the Corona virus has not been lethal on such a large, all-encompassing scale. But it could serve as a wake-up call for more and better prevention in the future, put differently: as a call to build a “preventive society”. When people look back to the year 2022 from the year 2200, will they think of the absence of mandatory vaccination as a dangerous anachronism? And will the unequal global distribution of vaccines be seen as an unbearable vice of our epoch? And will “human infection studies” still be dismissed as unethical if a dangerous new virus boards human bodies? If intergenerational justice means improving the life chances and living conditions of future generations to the largest possible extent, then its link to (the avoidance) of infectious diseases is obvious. We should protect future generations from foreseeable damage if we have the power to do so. “We” is humankind in its entirety. Politically, humanity is divided into many single nations. But biologically, as members of the same species, we share the same vulnerability regardless of ethnicity. The regular reader of this journal might wonder why this issue of IGJR has a different structure. An unprecedented pandemic calls for an unprecedented reaction and therefore IGJR 1/2021 and 2/2021 are special issues that deal with this disruptive event. We have invited several health experts, politicians and scholars alike to share their perspectives in short opinion pieces (instead of regular peer-reviewed articles). And we are exploring something new: the publication of a FRFG policy paper. This policy paper starts off with a historical overview on how pandemics have afflicted humanity in the past. It separates moral from legal duties and formulates “epidemiological imperatives” – the way of thinking of a responsible and solidary individual facing the task of preventing an outbreak of epidemics in a community. With the discovery of vaccines, and their availability, the catalogue of duties is increased by one more: to get the jabs as an act of solidarity with others, including future generations. This would prevent states from being forced to take disease control measures that bring about drastic collateral damage. During the first two years of the Corona pandemic, states have imposed lockdowns. The closure of schools has put a special burden on the youngest members of society. This could have been prevented during the second and the further waves. The policy paper also calls for more government funding for prophylactic vaccine research and for the designation of vaccines as “global public goods”. The issue then moves on to a section dedicated to opinion papers by various different authors. The first paper, written by Agnes Binagwaho and Kedest Mathewos (both from University of Global Health Equity, Rwanda), focuses on the issue of health inequity, a concern which has gained more and more traction during the Covid-19 pandemic. The paper examines how vaccine distribution during the pandemic was mainly focused on the global north and how such actions might affect future generations’ perception of what is just, fair and morally correct. The second paper, by Samantha Vanderslott (University of Oxford), focuses on the right and wrongdoings connected to pandemic preparedness and response. The third paper, authored by Rajeev Sadanandan (Health Systems Transformation Platform, India), talks about the lessons that can and should be drawn from child immunisations. The fourth paper, by Adriano Mannino (LMU and Parmenides Foundation, Munich), delves into the question how future generations will assess our actions and our response to the current pandemic. The fifth and final paper, written by Jörg Tremmel (FRFG and University Tübingen), is centered around the question whether human infection studies could have been implemented during the early stages of the pandemic to minimise deaths and severe infections. The issue concludes with two reviews on recent books by Alberto Giubilini and Katie Wright. In his review of Giubilini’s The Ethics of Vaccination, Marius Kunte notes that it contains a “thought-provoking plea” for individual, collective and institutional obligations to reach high vaccination rates. Judith Kausch-Zongo concludes her review of Wright’s Gender, Migration and the Intergenerational Transfer of Human Wellbeing with a special emphasis on the book’s empirical findings, and praises it in its entirety as “undoubtedly important”. Both books serve as poignant reminders of how sustainable societies can only emerge once the challenges revolving around its most vulnerable members have been properly addressed. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Philosophy, Psychiatry, & Psychology 12.4 (2005) 343-348 [Access article in PDF] Doomed by Nature: The Inevitable Failure of our Naturally Selected Functions Andreas De Block Keywords psychoanalysis, Darwinism, evolutionary psychiatry, pathogenic metaphysics In their very thoughtful and stimulating replies, the three commentators foreground several topics crucial for both psychoanalysis and philosophical psychiatry. In my short response, I focus primarily on what the commentators believe to be the paper's main (...) shortcomings. The first critique reads as follows: Freud never claimed that the Homo sapiens is a fundamentally sick animal, but in fact thought that normalcy is possible and that normal behavior need not be interpreted as neurotic, perverse or psychotic. The second is that current Darwinian psychiatry does not substantiate the view that Homo sapiens is essentially an ill animal, whatever Freud's position might be. Third and last, the proposal that all human beings are ill to the core seems to be more of a religious slogan than a scientifically useful description. What Freud Really Said A transhistorical approach to Freud's work is far from simple, considering that it spans a period of over forty years and that it underwent considerable changes during that time. Not only did Freud introduce some radically new concepts during that time, such as narcissism and the death drive. Also, he regularly changed his position on the aim of psychoanalytic therapy, the ontogenesis of anxiety, and the nature of human sexuality. That Freud sometimes saw homosexuality as an inborn drive did not keep him on other occasions from thinking that homosexual desire was a result of the repression or projection of an oedipal (heterosexual) drive. Examples like these show that any exegesis of Freud's writings inevitably has to deal with some tensions. Freud's work contains numerous apparent, as well as real, contradictions, so that it is no surprise at all that Katherine Morris can produce textual evidence "proving" that Freud never held the view I attribute to him. According to her, Freud thought that we are not all neurotics and that normalcy is possible.I do not deny that several passages in Freud's work underscore the possibility of non-neurotic normalcy. Indeed, Freudian theory even describes processes—sublimation, the transformation from Id to Ego, the resolution of the oedipal complex, among others—that explain how human beings can escape neurosis and other mental disorders. But Freud's illustrations of these mechanisms or processes make clear that he could not conceive [End Page 343] of a nonpathogenic psychodynamics. Consider, for instance, how Freud emphasizes throughout his study of Leonardo da Vinci that Leonardo's sublimations make him extremely vulnerable to psychic exhaustion or "neurasthenia" (1910). Freud never tires of repeating that there is only a gradual difference between a neurotic patient and Leonardo da Vinci, the sublimating ("healthy") artist and scientist.Morris (2005) is right, of course, in arguing that a gradual difference between normality and mental illness does not imply that there is no difference at all. Quantity should not be thought the opposite of quality, because small quantitative differences can transform an "articulation" into a "breach." To use Hegel's famous example, there is a continuum between 110° C and -10° C, but everybody knows that that water evaporates above 100° C and freezes below 0° C. Applied to mental disorders, quantitative differences in levels of testosterone and serotonin may lead to qualitative differences in behavior; in other words, categorical and dimensional approaches to mental illnesses are not mutually exclusive. Having established that, we now need to take a closer look at how Freud articulated the differences between seemingly normal individuals and the mentally ill.Freud held that neurosis, psychosis, and perversion are caused by the interplay between instincts and defense mechanisms. Further, he thought that the pathogenic instincts were almost exclusively sexual. Now, although it is true that he sometimes recognized that the fear of death and the death drive are important factors for psychic life (Deeley 2005) and for the etiology of psychosis, more often than not he interpreted the fear of death as a symbolization of... (shrink)

Multidrug-resistant Acinetobacter baumannii is recognized to be among the most difficult antimicrobial-resistant gram negative bacilli to control and treat. One of the major challenges that the pathogenic bacteria face in their host is the scarcity of freely available iron. To survive under such conditions, bacteria express new proteins on their outer membrane and also secrete iron chelators called siderophores. Antibodies directed against these proteins associated with iron uptake exert a bacteriostatic or bactericidal effect against A. baumanii in vitro, by blocking (...) siderophore mediated iron uptake pathways. Attempts should be made to discover peptides that could mimic protein epitopes and possess the same immunogenicity as the whole protein. Subsequently, theoretical methods for epitope prediction have been developed leading to synthesis of such peptides that are important for development of immunodiagnostic tests and vaccines. The present study was designed to in silico resolving the major obstacles in the control or in prevention of the diseases caused by A. baumannii. We exploited bioinformatic tools to better understand and characterize the Baumannii acinetobactin utilization structure of A. baumannii and select appropriate regions as effective B cell epitopes. In conclusion, amino acids 26–191 of cork domain and 321–635 of part of the barrel domain including L4–L9, were selected as vaccine candidates. These two regions contain functional exposed amino acids with higher score of B cell epitopes properties. Majority of amino acids are hydrophilic, flexible, accessible, and favorable for B cells from secondary structure point of view. (shrink)

This aricle discusses the similarity between the propagation of pathogens (viruses and worms) on computer networks and the proliferation of pathogens in cellular organisms (organisms with genetic material contained within a membrane-encased nucleus). It introduces several biological mechanisms which are used in these organisms to protect against such pathogens and presents security models for networked computers inspired by several biological paradigms, including genomics (RNA interference), proteomics (pathway mapping), and physiology (immune system). In addition, the study of epidemiological models for disease (...) control can inspire methods for controlling the spread of pathogens across multiple nodes of a network. It also presents results based on the authors’ research in immune system modeling. (shrink)

On September 27, 2016 people across the world looked down at their buzzing phones to see the AP Alert: “Baby born with DNA from 3 people, first from new technique.” It was an announcement met with confusion by many, but one that polarized the scientific community almost instantly. Some celebrated the birth as an advancement that could help women with a family history of mitochondrial diseases prevent the transmission of the disease to future generations; others held it unethical, citing medical (...) tourism and consequences for the future of the therapy. The child in question was actually born a few months earlier on April 6, 2016, but the research was published a few months later in the October edition of Fertility and Sterility. The mother carries DNA that could have given the baby Leigh Syndrome, a severe neurological disorder characterized by psychomotor regression that typically results in death between ages two and three.[1] Also known as subacute necrotizing encephalomyelopathy, Leigh Syndrome is caused by genetic mutations in mitochondrial DNA, which causes defective oxidative phosphorylation. Because people with this condition cannot re-form ATP, “demyleniation, gliosis, necrosis, spongiosis, or capillary proliferation”[2] can occur, thereby producing bilateral lesions across the central nervous system. The 36-year-old mother previously had four miscarriages and successfully birthed two children, both of whom survived less than six years due to the syndrome. For religious reasons, the mother opted for Spindle Nuclear Transfer instead of Pronuclear Transfer,[3] which many religious organizations oppose because it entails the destruction of fertilized eggs.[4] In Pronuclear Transfer, both the parent and donor egg are fertilized. The parent’s nuclear material is then removed from the egg containing mutated mitochondria and inserted into the fertilized donor egg—from which the original nuclear material has been removed and destroyed. Spindle Nuclear Transfer, on the other hand, removes the mother’s nuclear material from the egg with unhealthy mitochondria, then implants it into a donor’s egg. The newly created egg is then fertilized with the father’s sperm. This Spindle Nuclear Transfer was performed in Mexico by a team of doctors led by Dr. John Zhang, the founder of the New Hope Fertility Center in New York City. In their report, the doctors outline that five oocytes were successfully reconstituted, four of which developed into blastocysts. Only one was euploid: containing 46 XY chromosomes. Researchers then biopsied that blastocyst and found that the transmission rate of maternal mtDNA was, “5.10 ± 1.11% and the heteroplasmy level for 8993T>G was 5.73%.”[5] This indicates that at the blastocyst stage, around five percent of the mitochondria are from the original maternal egg with the mutation for Leigh Syndrome. After birth, they biopsied different tissues and found that they had an average of less than 1.60 ± 0.92% of transmitted mtDNA from the original maternal egg. The baby is reportedly doing well and the team of doctors concluded that “[h]uman oocytes reconstituted by SNT are capable of producing a healthy live birth. SNT may provide a novel treatment option in minimizing pathogenic mtDNA transmission from mothers to their babies."[6] Even when considered theoretically, Spindle Nuclear Transfer is controversial. Many doctors believe that the risks at this stage of research are too great. Dr. Trevor Stammers, a bioethicist at St. Mary’s University in London, points out: “We do not yet have a clear picture of the interaction between nuclear DNA and mitochondria.”[7] Others hold that faulty mitochondrial DNA can still be transferred during the procedure. Still more argue this technology could create problems because of germline modification.[8] Dr. Paul Knoepfler, a cell biologist at the UC Davis School of Medicine, explains: “Since this is uncharted territory and the children born from this technology would have heritable genetic changes, there are also significant unknown risks to future generations.”[9] However, proponents counter these arguments. They say the benefits outweigh the risks, as “mitochondrial replacement techniques [like Spindle Nuclear Transfer] would eliminate maternal transmission of mitochondrial disease… allowing a woman with a family history of mitochondrial diseases to ensure her children would not be affected.”[10] Additionally, experts say that no symptoms will occur if less than 20% of the transferred mitochondrial DNA is faulty.[11] And while opponents see potential germline modification as a problem, advocates answer that this could stop a family history of mitochondrial disease, which they deem a more serious concern. In this case specifically, however, there are more issues at hand. While the team of doctors did eliminate the possibility of germline modification by selecting a male embryo, there are other ethical concerns. Some argue that this case could be described as “medical tourism.” While New Hope Medical Clinic does maintain a branch in Mexico, Dr. Zhang stated that Mexico has “no rules.”[12] It is a country with underdeveloped regulations, making it difficult to confirm that doctors adhere to widely-held medical and ethical standards. Furthermore, while it is highly unlikely that the child will develop Leigh’s Syndrome, Dr. Dietrich Egli of the New York Stem Cell Foundation says the 5% mitochondrial transfer rate indicates that the technique “was not carried out well.”[13] He points to studies of embryos where the rate of mtDNA transfer was almost ten times lower. Spindle Nuclear Transfer is currently legal in the UK,[14] and many are hoping to see it legalized in the US, although Congress currently prohibits the FDA from considering applications that would entail trials in people.[15] While Dr. Zhang’s work is arguably revolutionary, many wonder if the manner in which this study was performed—in Mexico and with a high mitochondrial transfer rate—will impact the technology’s future in the US. Last week, Dr. Zhang presented the report to scientists gathered in Salt Lake City, saying that while science isn’t a race, it is “in a sense, a race for the family to find a cure, to find hope.”[16] Only time will tell if this study set back other families racing and hoping for a cure. References 1. "Leigh Syndrome." Genetics Home Reference, US National Library of Medicine, 25 Oct. 2016. Accessed 26 Oct. 2016. 2. McKusick, Victor A., and Ada Hamosh. "LEIGH SYNDROME; LS." Online Mendelian Inheritance in Man, Johns Hopkins University, 20 Jan. 2016. Accessed 30 Oct. 2016. 3. Zhang, J, H Liu, S Luo, A Chavez-Badiola, and Z Liu. "First live birth using human oocytes reconstituted by spindle nuclear transfer for mitochondrial DNA mutation causing Leigh syndrome." Fertility and Sterility, vol. 106, no. 3, 2016, pp. e375-76. Accessed 30 Oct. 2016. 4. Sample, Ian. "‘Three-parent’ babies explained: what are the concerns and are they justified?" The Guardian, 2 Feb. 2015. Accessed 30 Oct. 2016. 5. Zhang, et al. 6. Ibid. 7. Knapton, Sarah. "Three-parent babies: the arguments for and against." The Telegraph, 3 Feb. 2015. 8. Ibid. 9. Ibid. 10. "Mitochondrial Replacement Therapy FAQs." New York Stem Cell Foundation Research Institute, New York Stem Cell Foundation. Accessed 30 Oct. 2016. 11. Reardon, Sara. "‘Three-parent baby’ claim raises hopes — and ethical concerns." Nature, 28 Sept. 2016. Accessed 30 Oct. 2016. 12. Hamzelou, Jessica. "Exclusive: World’s first baby born with new “3 parent” technique." New Scientist, 27 Sept. 2016. Accessed 30 Oct. 2016. 13. Reardon, Sara. "‘Three-parent baby’ claim raises hopes — and ethical concerns." Nature, 28 Sept. 2016. Accessed 30 Oct. 2016. 14. "3-Person IVF: A Resource Page." Center for Genetics and Society, 24 Oct. 2016. Accessed 30 Oct. 2016. 15. Ritter, Malcolm. "Baby born with DNA from 3 people, first from new technique." Associated Press, 27 Sept. 2016. Accessed 30 Oct. 2016. 16. Chen, Daphne. "Controversy swirls around first three-parent baby." Deseret News, 19 Oct. 2016. Accessed 30 Oct. 2016. Works consulted Swetlitz, Ike. "FDA urged to approve ‘three-parent embryos,’ a new frontier in reproduction." STAT, 3 Feb. 2016. Accessed 30 Oct. 2016. (shrink)

Recently, oysters have been identified by the US Food and Drug Administration (USFDA) as a risky food to eat because they may or may not contain the pathogenic bacteria Vibrio parahaemolyticus. The USFDA's attempts to manage the risk manifest themselves in a “Quantitative Risk Assessment”, a report that attempts to quantify and predict the number of oyster eaters that will fall ill from Vibrio. In seeking to produce knowledge and eliminate uncertainty, the USFDA, through the use of a discourse of (...) quantification, does the opposite. Instead, we argue, documents such as risk assessments are best understood as kinds of rhetorical practice. According to this perspective, these documents are epistemologically and ontologically reductive, produce uncertainty, politicize the act of eating, and serve an ironic function. (shrink)

The two significant zoonotic bacterial infections that have remained a concern due to the complex dynamics involved in transmission and global prevalence are anthrax and brucellosis. The present paper attempts to address some of the most important zoonotic pathogens, highlighting their epidemiology, clinical manifestations, diagnosis, treatment, and prevention strategies. Anthrax is largely transmitted through direct contact with the infected animals or their products resulting in cutaneous, inhalational, and gastrointestinal forms, all with specific clinical outcomes and approaches for treatment. Similarly, the (...) genus Brucella primarily transmits brucellosis to humans by occupational exposure and consumption of contaminated animal products. Its presentation may be acute, chronic, or in relapse. Diagnosis is made by a combination of serological, molecular, and culture-based techniques, while the treatment focuses on antimicrobial regimens specific to the pathogen. However, this increases the problem of antimicrobial resistance, which makes their effective management challenging, necessitating an integrated approach. Mitigating risks through biosecurity measures, vaccination, public health education, and a One Health approach that includes human, animal, and environmental health, all facilitate prevention and control of an outbreak. Advanced surveillance and diagnostic technologies further support the prompt interventions to contain outbreaks. It then goes on to highlight the importance of interdisciplinarity for decreasing the global burden of zoonotic bacterial diseases. (shrink)

Resident microbiota do not just shape host immunity, they can also contribute to host protection against pathogens and infectious diseases. Previous reviews of the protective roles of the microbiota have focused exclusively on colonization resistance localized within a microenvironment. This review shows that the protection against pathogens also involves the mitigation of pathogenic impact without eliminating the pathogens (i.e., “disease tolerance”) and the containment of microorganisms to prevent pathogenic spread. Protective microorganisms can have an impact beyond their niche, interfering with (...) the entry, establishment, growth, and spread of pathogenic microorganisms. More fundamentally, we propose a series of conceptual clarifications in support of the idea of a “co-immunity,” where an organism is protected by both its own immune system and components of its microbiota. -/- . (shrink)

It has recently emerged that malarial, toxoplasmodial and related parasites contain a vestigial plastid (the organelle in which photosynthesis occurs in plants and algae). The function of the plastid in these obligate intracellular parasites has not been established. It seems likely that modern apicomplexans derive from photosynthetic predecessors, which perhaps formed associations with protists and invertebrates and abandoned autotrophy in favour of parasitism. Recognition of a third genetic compartment in these parasites proffers alternative strategies for combating a host of important (...) human and animal diseases. It also poses some fascinating questions about the evolutionary biology of this important group of pathogens. (shrink)

This essay offers a framework for analyzing whether government may justifiably intervene to contain the spread of disease. Nonconsensual transmission of dangerous pathogens is an inherently violent act. This framework therefore justifies government public health activities for the same reasons and only to the same extent as other government activities. Government public health interventions are legitimate only to the extent they minimize the amount of violence in society. Violence-minimization is a more egalitarian and welfare-enhancing rule than, for example, a rule (...) prescribing that government public health activities should minimize loss of life. (shrink)

The world’s scientific community must be in a state of constant readiness to address the threat posed by newly emerging infectious diseases. Whether the disease in question is SARS in humans or BSE in animals, scientists must be able to put into action various disease containment measures when everything from the causative pathogen to route(s) of transmission is essentially uncertain. A robust epistemic framework, which will inform decision-making, is required under such conditions of uncertainty. I will argue that this framework (...) should have reasoning at its center and, specifically, that forms of reasoning beyond deduction and induction should be countenanced by scientists who are confronted with emerging infectious diseases. In previous articles, I have presented a case for treating certain so-called traditional informal fallacies as rationally acceptable forms of argument that can facilitate scientific inquiry when little is known about an emerging disease. In this article, I want to extend that analysis by highlighting the unique features of these arguments that makes them specially adapted to cope with conditions of uncertainty. Of course, such a view of the informal fallacies must at least be consistent with the reasoning practices of scientists, and particularly those scientists (viz. epidemiologists) whose task it is to track and respond to newly emerging infectious diseases. To this end, I draw upon examples of scientific reasoning from the UK’s BSE crisis, a crisis that posed a significant threat to both human and animal health. (shrink)

This chapter contains section titled: Introduction Theoretical Perspectives Challenges Conclusion References Further Reading.

Resident microorganisms, known as the microbiota, are essential for many physiological functions including protection against pathogens. Microbiota is indeed required for proper immune system development and function, and can also host-independently protect against infections. Thus, a co-constructed view of host protection involving both host and microbiota, named ’co-immunity,’ has been proposed, and the idea of an ’immunological holobiont’ has been suggested. Yet this view of co-immunity might be too limited, as experimental work has shown that the immune system is involved (...) in functions other than protection, essentially development and repair. Microbiota, through co-immunity, is thereby most likely involved in these functions, although strong evidence is currently lacking. Moreover, as our point of view is mainly host-centered, we may miss the implications of co-immunity at broader scales, including cellular and population levels. Intriguingly, co-immunity effects could be beneficial for one function and/or one level, while being detrimental for others. All these elements should be taken into consideration for microbiota manipulation, in order to avoid potentially harmful side effects. (shrink)

Much research has explored behaviours that are linked with disgust sensitivity. Few studies, however, have been devoted to understanding how fixed or variable disgust sensitivity is. We therefore aimed to examine whether disgust sensitivity can change with the environment by repeatedly testing students whose environment was not changing as well as student cadets undergoing intensive training at an army camp. We found that an increase in the perceived harshness of the environment was associated with a decrease in pathogen disgust sensitivity. (...) Our results support the idea that disgust sensitivity is malleable depending on the environment. More specifically, we propose that in a harsh environment, where survival may be more difficult, pathogen disgust sensitivity may decrease to allow the consumption of available resources. (shrink)

It has been argued that people in areas with high pathogen loads will be more likely to avoid outsiders, to be biased in favor of in-groups, and to hold collectivist and conformist values. Cross-national studies have supported these predictions. In this paper we provide new pathogen codes for the 186 cultures of the Standard Cross-Cultural Sample and use them, together with existing pathogen and ethnographic data, to try to replicate these cross-national findings. In support of the theory, we found that (...) cultures in high pathogen areas were more likely to socialize children toward collectivist values (obedience rather than self-reliance). There was some evidence that pathogens were associated with reduced adult dispersal. However, we found no evidence of an association between pathogens and our measures of group bias (in-group loyalty and xenophobia) or intergroup contact. (shrink)

Within the same pathogen-stress framework as proposed by Fincher & Thornhill (F&T), we argue further that pathogen stress promotes matrilocal rather than patrilocal family ties which, in turn, slow down the process of modernity; and that pathogen stress promotes social learning or copying, including the adoption of foreign religions.

The development of technologies for the biopreservation of infectious organisms requires careful analysis of benefits and risks. This article reviews the regulatory landscape and oversight responsibilities in the United States in respect to pathogen biopreservation. Focused on two globally significant pathogens, Cryptosporidium and Plasmodium, the article explores advantages and potential risks of biopreservation concerning biosafety, biosecurity and biocontainment.

Skin-transmitted pathogens have threatened humans since ancient times. We investigated whether skin-transmitted pathogens were a subclass of disgust stimuli that evoked an emotional response that was related to, but distinct from, disgust and fear. We labelled this response “the heebie jeebies”. In Study 1, coding of 76 participants’ experiences of disgust, fear, and the heebie jeebies showed that the heebie jeebies was elicited by unique stimuli which produced skin-crawling sensations and an urge to protect the skin. In Experiment 2,350 participants’ (...) responses to skin-transmitted pathogen, fear-inducing, and disgust-inducing vignettes showed that the vignettes elicited sensations and urges which loaded onto heebie jeebies, fear, and disgust factors, respectively. Experiment 3 largely replicated findings from Experiment 2 using video stimuli. Results are consistent with the notion that skin-transmitted pathogens are a subclass of disgust stimuli which motivate behaviours that are functionally consistent with disgust yet qualitatively distinct. (shrink)

Genetic research into ageing, longevity and late-onset disease is becoming increasingly common. Yet, there is a paucity of knowledge related to clinical actionability and the return of pathogenic variants to otherwise healthy elderly individuals. Whether or not genetic research in the elderly should be managed differently from standard practices adapted for younger populations has not yet been defined. In this article, we provide an overview of ethical and practical challenges in preparing for a genetic study of over 14 000 healthy (...) Australians aged 70 years or older enrolled in the ASPirin in Reducing Events in the Elderly Healthy Ageing Biobank. At the time of consent, all participants in this study were free of life-threatening illness, cardiovascular disease or cognitive impairment. ASPREE is thus a cohort of healthy elderly individuals with seemingly minimal burden of genetic disease recruited without ascertainment bias. The cohort presents a unique opportunity to address the penetrance of known pathogenic variants in a population without disease symptoms; however, it also raises a number of ethical concerns regarding the interpretation and disclosure of variants with known clinical actionability. Some of the challenges include how to manage the interpretation, disclosure and actioning of pathogenic variants found in otherwise healthy elderly adults without disease symptoms, whether or not to disclose findings for the benefit of family members rather than elderly consented donors themselves, how to manage the return of genetic findings to the elderly individuals who are now in severe cognitive decline or terminal illness, how to ensure quality of information and clinical service upon disclosure of results to this demographic and how to prepare for the insurance implications of disclosing genetic information under Australian law. We discuss these and other dilemmas and propose a defensible plan of management. Trial registration number ISRCTN83772183. (shrink)

Anthropologists have documented substantial cross-society variation in people’s willingness to treat strangers with impartial, universal norms versus favoring members of their local community. Researchers have proposed several adaptive accounts for these differences. One variant of the pathogen stress hypothesis predicts that people will be more likely to favor local in-group members when they are under greater infectious disease threat. The material security hypothesis instead proposes that institutions that permit people to meet their basic needs through impartial interactions with strangers reinforce (...) a tendency toward impartiality, whereas people lacking such institutions must rely on local community members to meet their basic needs. Some studies have examined these hypotheses using self-reported preferences, but not with behavioral measures. We conducted behavioral experiments in eight diverse societies that measure individuals’ willingness to favor in-group members by ignoring an impartial rule. Consistent with the material security hypothesis, members of societies enjoying better-quality government services and food security show a stronger preference for following an impartial rule over investing in their local in-group. Our data show no support for the pathogen stress hypothesis as applied to favoring in-groups and instead suggest that favoring in-group members more closely reflects a general adaptive fit with social institutions that have arisen in each society. (shrink)

Archaea are microorganisms that are distinct from bacteria and eukaryotes. They are prevalent in extreme environments, and yet found in most ecosystems. They are a natural component of the microbiota of most, if not all, humans and other animals. Despite their ubiquity and close association with humans, animals and plants, no pathogenic archaea have been identified. Because no archaeal pathogens have yet been identified, there is a general assumption that archaeal pathogens do not exist. This review examines whether this is (...) a good assumption by investigating the potential for archaea to be or become pathogens. This is achieved by addressing: the diversity of archaea versus known pathogens, opportunities for archaea to demonstrate pathogenicity and be detected as pathogens, reports linking archaea with disease, and immune responses to archaea. In addition, molecular and genomic data are examined for the presence of systems utilised in pathogenesis. The view of this report is that, although archaea can presently be described as non‐pathogenic, they have the potential to be (discovered as) pathogens. The present optimistic view that there are no archaeal pathogens is tainted by a severe lack of relevant knowledge, which may have important consequences in the future. BioEssays 25:1119–1128, 2003. © 2003 Wiley Periodicals, Inc. (shrink)

In contrast to the great majority of mycobacterial species that are harmless saprophytes, Mycobacterium tuberculosis and other closely related tubercle bacilli have evolved to be among the most important human and animal pathogens. The need to develop new strategies in the fight against tuberculosis (TB) and related diseases has fuelled research into the evolutionary success of the M. tuberculosis complex members. Amongst the various disciplines, genomics and functional genomics have been instrumental in improving our understanding of these organisms. In this (...) review we will present some of the recent key findings on molecular determinants of mycobacterial pathogenicity and attenuation, the evolution of M. tuberculosis, genome dynamics, antigen mining for improved diagnostic and subunit antigens, and finally the identification of novel drug targets. The genomics revolution has changed the landscape of TB research, and now underpins our renewed efforts to defeat this deadly pathogen. (shrink)

Disgust is reasoned to operate in conjunction with the immune system to help protect the body from illness. However, less is known about the factors that impact the degree to which individuals invest in pathogen avoidance (disgust) versus pathogen management (prophylactic immunological activity). Here, we examine the role that one’s control over pathogen contact plays in resolving such investment trade-offs, predicting that (a) those from low control environments will invest less in pathogen-avoidance strategies and (b) investment in each of these (...) two strategies will occur in a compensatory fashion (i.e. they will be traded off with one other). Across four studies, we found support for these predictions, using a variety of manipulations and measures. By providing novel insights into how one’s control over pathogen exposure influences disgust sensitivity and immune system activity, the current research poses an important contribution to the literature on disgust, pathogen avoidance, and the immune system. (shrink)

Containment and support have traditionally been assumed to represent universal conceptual foundations for spatial terms. This assumption can be challenged, however: English in and on are applied across a surprisingly broad range of exemplars, and comparable terms in other languages show significant variation in their application. We propose that the broad domains of both containment and support have internal structure that reflects different subtypes, that this structure is reflected in basic spatial term usage across languages, and that it constrains children's (...) spatial term learning. Using a newly developed battery, we asked how adults and 4-year-old children speaking English or Greek distribute basic spatial terms across subtypes of containment and support. We found that containment showed similar distributions of basic terms across subtypes among all groups while support showed such similarity only among adults, with striking differences between children learning English versus Greek. We conclude that the two domains differ considerably in the learning problems they present, and that learning in and on is remarkably complex. Together, our results point to the need for a more nuanced view of spatial term learning. (shrink)

We question the plausibility of Fincher & Thornhill's (F&T's) argument that localised pathogen-host coevolution leads to out-groups having pathogens more damaging than those infecting one's own family or religious group.

Ärztliches Handeln unterliegt gesellschaftspolitischem Wandel. Ziel der hier vorgelegten qualitativen Fallstudie war es, Folgen gesellschaftlicher Konflikte auf ärztliches Handeln zu untersuchen. Zu diesem Zweck wurden Gruppendiskussionen mit Ärzten zu ihren Erfahrungen mit Geflüchteten 2015/16 in Sachsen und Bayern durchgeführt und tiefenhermeneutisch ausgewertet. An den Ergebnissen wird gezeigt, dass sowohl die Verwaltung als auch die politische Kultur und das gesellschaftliche Umfeld eine Funktion für Ärzte übernehmen, die als »Containment« begriffen werden kann. Zudem ließ sich so herausarbeiten, welche Konsequenzen es für das (...) ärztliche Handeln haben kann, wenn diese »Container«-Funktion im Zuge gesellschaftlicher Veränderungen bedroht ist. Während in zwei sächsischen Gruppen der Zusammenbruch des »Containments« den Rückgriff auf primäre Abwehrmechanismen notwendig machte, konnten die Ärzte in der bayrischen Gruppe ihr »Containment« aufrechterhalten und sich weiterhin als selbstwirksam erleben. (shrink)