Human Research Articles

Engineering of Saccharomyces cerevisiae as a platform strain for microbial production of sphingosine-1-phosphate.

Sphingosine-1-phosphate (S1P) is a multifunctional sphingolipid that has been implicated in regulating cellular activities in mammalian cells. Due to its therapeutic potential, there is a growing interest in developing efficient methods for S1P production. To date, the production of S1P has been achieved through chemical synthesis or blood extraction, but these processes have limitations such as complexity and cost. In this study, we generated an S1P-producing Saccharomyces cerevisiae strain by using metabolic engineering and introducing a heterologous sphingolipid biosynthetic pathway to demonstrate the possibility of microbial S1P production. To construct the sphingosine-producing S. cerevisiae strain, both the sphingolipid delta 4 desaturase gene (DES1) and the alkaline ceramidase gene (ACER1) derived from Homo sapiens were introduced into the genome of S. cerevisiae by deleting the dihydrosphingosine phosphate lyase gene (DPL1) and the sphingoid long-chain base kinase gene (LCB5) to prevent S1P degradation and byproduct formation, respectively. The sphingosine-producing strain, DDLA, produced sphingolipids containing sphingosine. In flask fed-batch fermentation, the DDLA strain showed a higher production level of sphingosine under aerobic conditions with high initial cell density. The S1P-producing strain was generated by expressing the human sphingosine kinase gene (SPHK1) under the control of the inducible promoter, while deleting the ORM1 gene involved in the regulation of sphingolipid biosynthesis. The S1P-producing strain, DDLAOgS, exhibited the highest sphingosine production level under fed-batch fermentation in a bioreactor, achieving a 2.6-fold increase compared to flask fermentation. S1P biosynthesis in the DDLAOgS strain was verified by qualitative analysis using electrospray ionization mass spectrometry (ESI-MS). We successfully developed a metabolically engineered S. cerevisiae as a platform strain for microbial production of S1P by introducing an exogenous pathway of sphingolipids metabolism. The engineered yeast strains showed significant capabilities for sphingolipid production, including S1P. To our knowledge, this is the first report demonstrating that engineered S. cerevisiae can be a major platform strain for producing microbial S1P.

MiRNATissueAtlas 2025: an update to the uniformly processed and annotated human and mouse non-coding RNA tissue atlas.

MiRNAs represent a non-coding RNA class that regulate gene expression and pathways. While miRNAs are evolutionary conserved most data stems from Homo sapiens and Mus musculus. As miRNA expression is highly tissue specific, we developed miRNATissueAtlas to comprehensively explore this landscape in H. sapiens. We expanded the H. sapiens tissue repertoire and included M. musculus. In past years, the number of public miRNA expression datasets has grown substantially. Our previous releases of the miRNATissueAtlas represent a great framework for a uniformly pre-processed and label-harmonized resource containing information on these datasets. We incorporate the respective data in the newest release, miRNATissueAtlas 2025, which contains expressions from 9 classes of ncRNA from 799 billion reads across 61 593 samples for H. sapiens and M. musculus. The number of organs and tissues has increased from 28 and 54 to 74 and 373, respectively. This number includes physiological tissues, cell lines and extracellular vesicles. New tissue specificity index calculations build atop the knowledge of previous iterations. Calculations from cell lines enable comparison with physiological tissues, providing a valuable resource for translational research. Finally, between H. sapiens and M. musculus, 35 organs overlap, allowing cross-species comparisons. The updated miRNATissueAtlas 2025 is available at https://www.ccb.uni-saarland.de/tissueatlas2025.

Evidence for the oldest Middle Palaeolithic cave occupation in the Romanian Carpathians

ABSTRACTThe Middle and Upper Palaeolithic sites in the Carpathians and Danube lowlands constitute key contexts for tracing the dispersal of Homo sapiens into central‐western Europe and the replacement of Homo neanderthalensis. Surprisingly, the Romanian archaeological inventory lacks transitional technologies and only a few sites have been systematically excavated and numerically dated, explaining the incomplete understanding of the Middle Palaeolithic and hence Neanderthal population dynamics. Here we present new age constraints for the Abri 122/1200 and Peștera Mare caves in the Romanian Carpathians, obtained by radiocarbon dating of charcoal and bone and by optically stimulated luminescence (OSL) dating of cave sediments. Methodological issues and the method's upper limit cause grossly underestimated radiocarbon ages for charcoal from Abri 122/1200 and provide only minimum ages (>41–60 14C ka bp) for bones from Peștera Mare cave. However, the OSL ages suggest Middle Palaeolithic cave occupation in the Carpathians since early Marine Isotopic Stage (MIS) 7 and lasting at least until MIS 5. These ages reinforce the vast potential of Carpathian cave sites in solidifying our understanding of Neanderthal dynamics in the region and their habitats. We discuss the reliability of this new chronology and the archaeological implications for the Middle Palaeolithic of neighbouring areas.

A bioinformatic approach for the prediction and functional classification of Toxoplasma gondii long non-coding RNAs.

Long non-coding RNAs (lncRNAs) have emerged as significant players in diverse cellular processes, including cell differentiation. Advancements in computational methodologies have facilitated the prediction of lncRNA functions, enabling insights even in non-model organisms like pathogenic parasites, in roles such as parasite development, antigenic variation, and epigenetics. In this work, we focus on the apicomplexan Toxoplasma gondii differentiation process, where the infective stage, tachyzoite, can develop into the cysted stage, bradyzoite, under stress conditions. Using a publicly available transcriptome dataset, we predicted putative lncRNA sequences associated with this differentiation process. Notably, a substantial proportion of these putative lncRNAs exhibited stage-specific expression, particularly at the bradyzoite stage. Furthermore, co-expression patterns between coding transcripts and putative TglncRNAs suggest their involvement in shared processes, such as bradyzoite development. Putative TglncRNA loci analysis revealed their potential influence on the expression of nearby coding genes, including subtelomeric genes unique to the T. gondii genome. Finally we propose a k-mer analysis approach to predict putative functional relationships between characterized lncRNAs from model organisms like Homo sapiens and the putative T. gondii lncRNAs. Our perspective led to predict putative T. gondii lncRNA that potentially could act mediating DNA damage repair pathways, opening a new study field to validate this kind of adaptive mechanisms of T. gondii in response to stress conditions.

A pre- and postnatal immune challenge influences muscle growth and metabolism in weaned pigs.

The in-utero environment is key to both fetal and postnatal growth and development. The objective of this study was to determine if administration of an acute low-dose lipopolysaccharide (LPS) to gestating sows during mid to late gestation and post-weaning would alter the offsprings metabolomic profile of the longissimus dorsi (LD) and muscle ultrastructure. Pregnant Camborough sows were randomly assigned to receive LPS (LPS; n= 7) at a dose of 2.5 μg/kg or saline (CON; n = 7) on 78 ± 1.8 d of gestation. At weaning (21 ± 1.3 d of age), barrows (CON n = 17; LPS n = 17) from each treatment were selected to receive a secondary LPS. Barrows were administered the secondary LPS challenge at a dose of 10 μg/kg 7 d post weaning. Twenty-four h after the postnatal LPS dose, barrows (31 ± 1.3 d of age) were euthanized, and each LD was removed. The left LD was utilized for morphometric measurements. Two samples from the medial section of the right LD were preserved for immunohistochemical measurements and metabolomic analyses. Mass spectral data were deconvoluted, aligned, and annotated using MS-DIAL. Univariate and multivariate analyses were conducted using MetaboAnalyst. Pathway analysis was conducted and compared to the Homo sapiens pathway library. Morphometric and immunohistochemical measurements were analyzed using the MIXED procedure of SAS version 9.4. Significance for all analyses was declared at P ≤ 0.05 and tendencies were considered at P ≤ 0.10. Average diameter of myosin heavy chain (MHC) type I and IIB/X fibers was increased (P ≤ 0.048) in LPS offspring compared with CON. Average cross-sectional area was increased (P = 0.030) in MHC IIB/X fibers and tended to be increased (P = 0.080) in MHC I fibers of LPS offspring. There were no differences (P ≥ 0.186) between treatment groups for total nuclei or nuclei positive for MYF5, PAX7, or MYF5 and PAX7 nuclei. Metabolomic analyses identified 14 differentially expressed (P < 0.05) metabolites in the LD between treatment groups. There were 10 metabolites within the LD that tended (P ≤ 0.096) to differ between treatment groups. Thus, this study shows that in-utero immune stimulation using LPS in gestating sows and a subsequent LPS challenge postnatally alters the metabolomic profile and muscle ultrastructure of the LD in weaned pigs.

Transhumanism and evolutionary psychology: a dialogue about the future of human nature

The article explores the philosophical dialogue between transhumanism and evolutionary psychology regarding the limits and consequences of the technological transformation of human nature. The growing relevance of this debate is analyzed in the context of the rapid development of genetics, nanotechnology and robotics, which open up unprecedented opportunities for changing human nature. The main provisions of transhumanism are considered, which, continuing the ideas of the Enlightenment, offers a radical vision of the future, where humanity can consciously direct its own evolution with the help of technology. The position of evolutionary psychology is highlighted, which, based on an understanding of the natural mechanisms of the development of the human species, warns against hasty intervention in a complex system of adaptive mechanisms that have been formed over millions of years. The paper analyzes in detail the works of leading representatives of both directions, including J. Huxley and Gr. Flow from the side of transhumanism, as well as critical views of F. Fukuyama and L. Kass. Special attention is paid to the research of evolutionary psychologists, who provide scientific justification for the concept of universal human nature and warn against the risks of “planned evolution”. A fundamental contradiction has been revealed between the views of transhumanists, who consider human nature as plastic and ready for technological changes, and evolutionary psychologists, who consider it a fixed reality formed by long evolution. It is emphasized that modern technologies create fundamentally new conditions for human existence that go beyond the traditional enlightened understanding of science. The study shows that although technological development of mankind has already changed our nature, further radical changes require careful consideration and study. The main problem of “planned evolution” is determined by the risk of uncontrolled acceleration of natural evolutionary processes without understanding all possible consequences.

Carl Sagan and libraries: An original thinker remembered

This article considers the legacy of astronomer Carl Sagan (1934–1996), whose book The Dragons of Eden presents a complete etiology of the library in the context of human evolution. Essential to Sagan's theory of the origins of the library is the concept of extrasomatic information, or knowledge stored outside the body. Surprising evidence on behalf of Sagan's theory has been presented in recent years by Nobel-Prize-winning neuroscientist Eric Kandel and others: that the human brain has not significantly grown for 50,000 years, presumably not due to evolutionary stagnation, but because cultural evolution has superseded biological evolution in Homo sapiens, an advance which has led to us becoming the dominant species on Earth.

Quercetin Protects Goat Sperm Motility by Inhibiting Neutrophil Extracellular Traps and Maintaining Plasma Membrane and Acrosome Integrity

Enhancing or protecting sperm motility has always been a pivotal approach to improving the ewe pregnancy rate. Sperm motility is highly susceptible to the immune status of the reproductive tract. Neutrophil extracellular traps (NETs) have been demonstrated to capture sperm and impair its motility in human, swine, and goat species. Quercetin is a flavonoid derived from Cuscuta Chinensis Lam., which can protect sperm from oxidative damage. In this study, we investigated whether inflammation decreases sperm motility and tried to clarify the potential protective mechanism of quercetin on goat sperm motility. Sperm-triggered NETs were analyzed by immunofluorescence analysis. Sperm acrosome integrity was detected by using giemsa staining. Quercetin exhibited no cytotoxicity towards sperm and PMNs within the concentration range of 20–80 μM. PMNs impaired both the survival rate and rapid linear motility of sperm, while quercetin significantly enhanced these parameters. PMNs captured sperm through NETs composed of DNA, citrullinated histone 3 (citH3), and neutrophil elastase (NE); however, quercetin effectively inhibited the release of sperm-stimulated NETs. The stimulation of PMNs with sperm resulted in a significant increase in levels of ROS and MDA, which decreased by quercetin. Moreover, PMNs caused integrity violation to both the plasma membrane and acrosome in sperm; this effect was significantly alleviated by quercetin. In conclusion, quercetin effectively ameliorated PMN-reduced sperm motility through the inhibition of NETs and oxidative stress, and preserving sperm plasma membrane and acrosome integrity, thereby providing preliminary insights into the underlying mechanisms and theoretical support for the development of potential sperm protectors.

Middle Pleistocene teeth from Arbreda Cave (Serinyà, northeastern Iberian Peninsula).

We report the discovery and description of three human teeth from the Middle Paleolithic archaeological levels of Arbreda Cave (Serinyà, Catalonia, NE Iberian Peninsula). The teeth, two molars (one right dm2 and one right M2) from Level N (older than 120 kyr) and one P3 from Level J (dated between 71 and 44 kyr), were morphologically described based on microCT images and compared with Neanderthal and Homo sapiens specimens. The teeth belong to a minimum of three individuals: one adult and one infant from Level N and one juvenile from Level J. The premolar from Mousterian Level J, the best preserved of the three teeth, exhibits characteristics to those from our comparative sample of Homo neanderthalensis, such as the crown measurements, EDJ traits, enamel thickness and volume of the pulp cavity. In contrast to the clear Neanderthal characteristics observed in the P3 from Level J, the high degree of dental wear and poor state of preservation precludes definitive taxonomic designations of the two teeth from Level N. However, the crown dimensions and some tissue proportions are consistent with a probable assignation to Homo neanderthalensis. The teeth from Level N come from a context of long and recurrent occupations of the cave, whereas the archaeological context of the tooth from Level J is indicative of short and seasonal occupations of the cave, which may indicate a change in the lifestyle strategies of the last Neanderthals of the Iberian Peninsula.

Bio-characteristics, tissue expression of miR-375 in hypothalamic-pituitary-ovarian axis and its regulation in reproduction-related diseases

Our study concentrated on the expression of miRNA-375 in the hypothalamic-pituitary-gonadal axis of female Hu sheep. The investigation involved cloning the precursor sequence of miR-NA-375, followed by comparison with database entries and subsequent Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. In our approach, we obtained ovaries, thalamus, cerebellum, brain, uterus, pituitary gland, hypothalamus, and pineal gland from fertile but nonpregnant Hu ewes. MiRNA extraction kit was used to extract miRNA from the above eight tissues. Real-time fluorescent quantitative polymerase chain reaction was used to evaluate the role of miR-375 in the hy-pothalamic-pituitary-gonadal axis. The results of miR-375 precursor sequence cloning were compared with those of Anopheles gambiae, Apis mellifera, Bos taurus, Drosophila melanogaster, Danio rerio, Fugu rubripes, Gallus gallus, Homo sapiens, Monodelphis domestica, Macaca mulatta, Mus musculus, Pan troglodytes, Rattus norvegicus, Tetraodon nigroviridis, Xenopus tropicalis miR-375 in miRBase database. It was found that oar-miR-375 was highly conserved. Notably, miR-375 expression in the pineal gland was significantly higher (p < 0.01) than that in the ovaries, thalamus, cerebellum, brain, uterus, pituitary gland, hypothalamus. The study also involved predicting miR-375 target genes. GO and KEGG enrichment analyses of these predicted target genes revealed that miR-375 is involved in 182 biological processes, affects 186 cellular components, and participates in 184 molecular functions. In terms of pathway enrichment, miR-375 was linked to nine pathways, including the Hippo, Wnt, and mTOR signaling pathways. This study has validated the interaction between miR-375 and its target gene FZD4, which can be recognized and bound to produce effects. These findings lead to the inference that miR-375 may play a crucial regulatory role in sheep reproduction through the Hippo pathway and Wnt pathway, laying a foundation for further exploration of miR-375’s role in this domain.

TRANCE STEREOTYPIES IN HUMAN AND PRIMATE PANTOMIMICRY

The authors reviewed and analysed Russian and foreign experimental studies on pantomimic stereotypes. Initially, stereotypical behaviuor was negatively evaluated. Modern research considers adaptive functions and possibilities of self-stimulation as a way to harmonise emotional and mental state. A comparative analysis of circular, pendulum and diagonal movements in children and Old World monkeys was conducted using an ethological approach to the study of behavioural patterns. Human observations were conducted in the psychoneurological department of Silischeva Astrakhan Regional Children’s Clinical Hospital, 40 preschool children with mental dysontogenesis participated. Five laboratory macaques and a family of hamadryas baboons kept in an aviary with homologous kinesics were observed in Sukhumi nursery. According to the authors’ team, walking (running) in a circle and diagonally, swinging the body “right-to-leftˮ in the pantomimic production of children and monkeys are associated with self-stimulation of an altered state of consciousness. Trance stereotypes divert attention from external stressors and stimuli and harmonise mental homeostasis. The study may be of interest to anthropologists, primatologists, specialists in the study of the psyche and pathological behaviour of animals and Homo sapiens.

Coinfection of EBV with other pathogens: a narrative review

The Epstein-Barr viwrus (EBV) is a common herpesvirus that affects more than 90% of people worldwide. Even while EBV infections are frequently asymptomatic, they can cause autoimmune diseases and a number of cancers, especially in those with impaired immune systems. The intricate relationships between EBV and other coinfecting pathogens, including as human immunodeficiency virus (HIV), human papilloma virus (HPV), cytomegalovirus (CMV), and Plasmodium species, are examined in this study. We investigated the fundamental processes of these coinfections, their effects on the course of the disease, and their practical ramifications. The study reviewed how co-infections with EBV might modify immune responses, promote oncogenesis, and make treatment plans more challenging. In this review, we also discussed current therapeutic strategies, such as targeted molecular interventions, EBV vaccines, and adoptive T-cell therapy. The review underscores the need for more research to provide more focused and effective therapies that address the mutually reinforcing effects of numerous infections in disorders linked with EBV.

Archaic introgression contributed to shape the adaptive modulation of angiogenesis and cardiovascular traits in human high-altitude populations from the Himalayas.

It is well established that several Homo sapiens populations experienced admixture with extinct human species during their evolutionary history. Sometimes, such a gene flow could have played a role in modulating their capability to cope with a variety of selective pressures, thus resulting in archaic adaptive introgression events. A paradigmatic example of this evolutionary mechanism is offered by the EPAS1 gene, whose most frequent haplotype in Himalayan highlanders was proved to reduce their susceptibility to chronic mountain sickness and to be introduced in the gene pool of their ancestors by admixture with Denisovans. In this study, we aimed at further expanding the investigation of the impact of archaic introgression on more complex adaptive responses to hypobaric hypoxia evolved by populations of Tibetan/Sherpa ancestry, which have been plausibly mediated by soft selective sweeps and/or polygenic adaptations rather than by hard selective sweeps. For this purpose, we used a combination of composite-likelihood and gene network-based methods to detect adaptive loci in introgressed chromosomal segments from Tibetan WGS data and to shortlist those presenting Denisovan-like derived alleles that participate to the same functional pathways and are absent in populations of African ancestry, which are supposed to do not have experienced Denisovan admixture. According to this approach, we identified multiple genes putatively involved in archaic introgression events and that, especially as regards TBC1D1, RASGRF2, PRKAG2, and KRAS, have plausibly contributed to shape the adaptive modulation of angiogenesis and of certain cardiovascular traits in high-altitude Himalayan peoples. These findings provided unprecedented evidence about the complexity of the adaptive phenotype evolved by these human groups to cope with challenges imposed by hypobaric hypoxia, offering new insights into the tangled interplay of genetic determinants that mediates the physiological adjustments crucial for human adaptation to the high-altitude environment.

Archaic introgression contributed to shape the adaptive modulation of angiogenesis and cardiovascular traits in human high-altitude populations from the Himalayas

It is well established that several Homo sapiens populations experienced admixture with extinct human species during their evolutionary history. Sometimes, such a gene flow could have played a role in modulating their capability to cope with a variety of selective pressures, thus resulting in archaic adaptive introgression events. A paradigmatic example of this evolutionary mechanism is offered by the EPAS1 gene, whose most frequent haplotype in Himalayan highlanders was proved to reduce their susceptibility to chronic mountain sickness and to be introduced in the gene pool of their ancestors by admixture with Denisovans. In this study, we aimed at further expanding the investigation of the impact of archaic introgression on more complex adaptive responses to hypobaric hypoxia evolved by populations of Tibetan/Sherpa ancestry, which have been plausibly mediated by soft selective sweeps and/or polygenic adaptations rather than by hard selective sweeps. For this purpose, we used a combination of composite-likelihood and gene network-based methods to detect adaptive loci in introgressed chromosomal segments from Tibetan WGS data and to shortlist those presenting Denisovan-like derived alleles that participate to the same functional pathways and are absent in populations of African ancestry, which are supposed to do not have experienced Denisovan admixture. According to this approach, we identified multiple genes putatively involved in archaic introgression events and that, especially as regards TBC1D1, RASGRF2, PRKAG2, and KRAS, have plausibly contributed to shape the adaptive modulation of angiogenesis and of certain cardiovascular traits in high-altitude Himalayan peoples. These findings provided unprecedented evidence about the complexity of the adaptive phenotype evolved by these human groups to cope with challenges imposed by hypobaric hypoxia, offering new insights into the tangled interplay of genetic determinants that mediates the physiological adjustments crucial for human adaptation to the high-altitude environment.

Metabolic capabilities are highly conserved among human nasal-associated Corynebacterium species in pangenomic analyses.

Pangenomic analysis with estimation of functional capabilities facilitates our understanding of the full biologic diversity of bacterial species. We performed systematic genomic, phylogenomic, and pangenomic analyses with qualitative estimation of the metabolic capabilities of four common human nasal Corynebacterium species, along with focused experimental validations, generating a foundational resource. The prevalence of each species in human nasal microbiota is consistent with the common coexistence of at least two species. We identified a notably high level of metabolic conservation within and among species indicating limited options for species to occupy distinct metabolic niches, highlighting the importance of investigating interactions among nasal Corynebacterium species. Comparing strains from two continents, C. pseudodiphtheriticum had restricted geographic strain distribution characterized by an evolutionarily recent loss of assimilatory sulfate reduction in U.S. strains. Our findings contribute to understanding the functions of Corynebacterium within human nasal microbiota and to evaluating their potential for future use as biotherapeutics.

Amyotrophic lateral sclerosis represents corticomotoneuronal system failure.

Several decades have passed since the anterograde corticomotoneuronal hypothesis for amyotrophic lateral sclerosis (ALS) was proposed. The intervening years have witnessed its emergent support based on anatomical, pathological, physiological, neuroimaging, and molecular biological studies. The evolution of an extensive corticomotoneuronal system appears restricted to the human species, with ALS representing a uniquely human disease. While some, very select non-human primates have limited corticomotoneuronal projections, these tend to be absent in all other animals. From a general perspective, the early clinical features of ALS may be considered to reflect failure of the corticomotoneuronal system. The characteristic loss of skilled motor dexterity involving the limbs, and speech impairment through progressive bulbar dysfunction specifically involve those motor units having the strongest corticomotoneuronal projections. A similar explanation likely underlies the unique "split phenotypes" that have now been well characterized in ALS. Large Betz cells and other pyramidal corticomotoneuronal projecting neurons, with their extensive dendritic arborization, are particularly vulnerable to the elements of the ALS exposome such as aging, environmental stress and lifestyle changes. Progressive failure of the proteosome impairs nucleocytoplasmic shuffling and induces toxic but soluble TDP-43 to aggregate in corticomotoneurons. Betz cell failure is further accentuated through dysfunction of its profuse dendritic arborizations. Clarification of system specific genomes and neural networks will likely promote the initiation of precision medicine approaches directed to support the key structure that underlies the neurological manifestations of ALS, the corticomotoneuronal system.

“Planetary phase shift” as a new systems framework to navigate the evolutionary transformation of human civilisation

Purpose The paper aims to address a gap in foresight study and practice relating to the lack of unifying theoretical systems frameworks capable of examining empirical data from across a wide range of different ecological, social, political and economic systems. It attempts to develop a new “collective forward intelligence” that can not only make sense of these disparate trends and processes as symptoms of a wider planetary system but also, on this basis, construct accurate and plausible future scenarios to underpin national and international decision-making. Design/methodology/approach This study conducts a transdisciplinary integration of C. S. Holling’s adaptive cycle with phase-transition phenomena across biology, physics and chemistry, applied on societal and civilisational scales. A systems methodology is then applied to integrate historical and empirical data across the energy, food, transport, materials and information sectors of civilisation’s production system. Findings The paper develops planetary phase shift theory as a new collective forward intelligence framework for foresight study and practice, formalising the notion that humanity has arrived at an unprecedented historic and geological turning point. It finds that multiple global crises across both earth and human systems are symptoms of the last stages of the life-cycle of global industrialisation civilisation, which is the potential precursor either for collapse, or for a new civilisational life-cycle that may represent a new stage in the biological and cultural evolution of the human species. Research limitations/implications The research sets out a new empirically grounded theoretical framework for complex scenario analysis. This can develop more robust approaches to foresight study and practice, scenario development and forecasting. It suggests the need for a new research programme to understand the dynamics of the planetary phase shift and its diverse implications for societies, industry, technology and politics. The research is limited in that the current paper does not explore how it can be applied in this way. It identifies broad scenarios for a post-industrial civilisational life-cycle but does not identify the variety of complex subsets of these. Practical implications The paper provides powerful practical implications to develop new methodology based on planetary phase shift theory for strategic planning, risk assessment and management, as well as public policy and decision-making. Social implications The paper suggests the urgency and necessity of bold and radical societal transformation and implies key areas for civil society to focus on in innovating new values, worldviews and operating systems with a focus on the next life-cycle. Originality/value To the best of the author’s knowledge, this paper provides the first integrated transdisciplinary theoretical and empirical framework to understand how the interplay of earth system crises, societal change and technology disruptions is driving large-scale civilisational transformation with complex local ramifications.

Morphological discrimination of human lice (Anoplura: Pediculidae) by eggs’ cap-like operculum

Human lice have long been parasites of humans and are responsible for several epidemics in human medical history. However, their morphology, particularly head and body lice, remains very similar. In this study, we discriminate human louse species based on the number, shape and size of aeropyles (respiratory pores) of the egg operculum as well as the size of the respiratory orifice in the aeropyles. For this purpose, lice and eggs were collected from infested patients referring to Parasitology Department of Avicenne Hospital (Bobigny, France) and analyzed morphologically. The microscopic examination of the aeropyles revealed a large variation in the number ranging from 5 to 12 for head lice, 10 to 16 for body lice and 13 to 18 for pubic lice with a statistically distinct average of 8.3, 12.9 and 15.7, respectively. Although the length of the head and body louse eggs were almost similar, the width of body louse eggs were bigger than those of head louse (412.9 μm and 363.5 μm, respectively), while pubic louse eggs had the smallest length (692.9 μm) and width (286.1 μm). In addition, pubic louse eggs had a greater operculum length and width (253.7 μm length and 220.7 μm width) than head (230.6 μm length and 210.2 μm width) and body lice (227.9 μm length and 199.9 μm width). Moreover, pubic lice had the smallest average aeropyle size (41.2 μm) compared to head (51.1 μm) and body lice (49.1 μm). The respiratory orifice on the aeropyles of head and body lice (9.9 μm) were almost twice as big as those of pubic lice (4.9 μm). There was an inverse correlation between the number of aeropyles and their size in head, body and pubic lice. These findings are helpful in accurate identification of human louse species using their eggs, which could be useful for control management strategies against these ectoparasites.

Quantitative Analysis of the Brachialis and Triceps Brachii Insertion Sites on the Proximal Epiphysis of the Ulna in Modern Hominid Primates and Fossil Hominins.

In several species of hominid primates with different types of locomotor behavior, we quantitatively studied the insertion sites of the brachialis and triceps brachii on the proximal epiphysis of the ulna. Our main objective was to evaluate the possibility of using the anatomical features of these insertion sites to infer the locomotor behavior of different species of fossil hominins. We measured the area of these muscle insertion sites using 3D bone meshes and obtained the value of each insertion site relative to the total size of the two insertion sites for each of the species studied. We also compared these relative values of the osteological samples with the relative mass of the brachialis and triceps brachii, which we obtained by dissecting these muscles in the same primate species. The relative values for the brachialis insertion were highest in orangutans, followed by bonobos, chimpanzees, gorillas, and humans. Fossil Australopithecus and Paranthropus had values similar to those of bonobos, while fossil Homo had values similar to those of Homo sapiens. The observed similarity in ulnar attachment sites between Australopithecus and Paranthropus and extant bonobos suggest that these hominins used arboreal locomotion to complement their bipedalism. These adaptations to arboreal locomotion were not observed in Homo.

Chronic pain-induced methylation in the prefrontal cortex targets gene networks associated with cognition and Alzheimer’s disease

Chronic pain is prevalent among aging adults. Epidemiologic evidence has demonstrated that individuals with chronic pain have accelerated memory decline and increased probability of dementia. Neurophysiologic, molecular, and pharmacologic hypotheses have been proposed to explain the relationship between chronic pain and cognitive decline, but there remains currently limited evidence supporting any of these. Here, we integrate multi-omic data across human cohorts and rodent species and demonstrate that methylation in the prefrontal cortex induced by chronic pain specifically targets transcriptional networks associated with cognitive ability, memory, and Alzheimer’s disease in humans. We validate this with multiple independent data sets and identify cortical microglia as a likely mechanism by which chronic pain can increase dementia risk. Our analyses support the molecular hypothesis for the role of chronic pain in cognitive decline and identifies several potential therapeutic targets.