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Mammalian face as an evolutionary novelty (2021)

Higashiyama, Hiroki ; Koyabu, Daisuke ; Hirasawa, Tatsuya ; [weitere]

National Academy of Sciences

In: PNAS - Proceedings of the National Academy of Sciences of the United States of America. 2021; 118(44): e2111876118. Published 2021 Oct 29. doi: 10.1073/pnas.2111876118.

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Publikationsdatum: 2021-10-29

Beschreibung: The anterior end of the mammalian face is characteristically composed of a semimotile nose, not the upper jaw as in other tetrapods. Thus, the therian nose is covered ventrolaterally by the “premaxilla,” and the osteocranium possesses only a single nasal aperture because of the absence of medial bony elements. This stands in contrast to those in other tetrapods in whom the premaxilla covers the rostral terminus of the snout, providing a key to understanding the evolution of the mammalian face. Here, we show that the premaxilla in therian mammals (placentals and marsupials) is not entirely homologous to those in other amniotes; the therian premaxilla is a composite of the septomaxilla and the palatine remnant of the premaxilla of nontherian amniotes (including monotremes). By comparing topographical relationships of craniofacial primordia and nerve supplies in various tetrapod embryos, we found that the therian premaxilla is predominantly of the maxillary prominence origin and associated with mandibular arch. The rostral-most part of the upper jaw in nonmammalian tetrapods corresponds to the motile nose in therian mammals. During development, experimental inhibition of primordial growth demonstrated that the entire mammalian upper jaw mostly originates from the maxillary prominence, unlike other amniotes. Consistently, cell lineage tracing in transgenic mice revealed a mammalian-specific rostral growth of the maxillary prominence. We conclude that the mammalian-specific face, the muzzle, is an evolutionary novelty obtained by overriding ancestral developmental constraints to establish a novel topographical framework in craniofacial mesenchyme.

Print ISSN: 0027-8424

Digitale ISSN: 1091-6490

Thema: Biologie , Medizin , Allgemeine Naturwissenschaft

Publiziert von National Academy of Sciences

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Power spectra reveal distinct BOLD resting-state time courses in white matter (2021)

Li, Muwei ; Gao, Yurui ; Ding, Zhaohua ; [weitere]

National Academy of Sciences

In: PNAS - Proceedings of the National Academy of Sciences of the United States of America. 2021; 118(44): e2103104118. Published 2021 Oct 29. doi: 10.1073/pnas.2103104118.

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Publikationsdatum: 2021-10-29

Beschreibung: Accurate characterization of the time courses of blood-oxygen-level–dependent (BOLD) signal changes is crucial for the analysis and interpretation of functional MRI data. While several studies have shown that white matter (WM) exhibits distinct BOLD responses evoked by tasks, there have been no comprehensive investigations into the time courses of spontaneous signal fluctuations in WM. We measured the power spectra of the resting-state time courses in a set of regions within WM identified as showing synchronous signals using independent components analysis. In each component, a clear separation between voxels into two categories was evident, based on their power spectra: one group exhibited a single peak, and the other had an additional peak at a higher frequency. Their groupings are location specific, and their distributions reflect unique neurovascular and anatomical configurations. Importantly, the two categories of voxels differed in their engagement in functional integration, revealed by differences in the number of interregional connections based on the two categories separately. Taken together, these findings suggest WM signals are heterogeneous in nature and depend on local structural-vascular-functional associations.

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Thema: Biologie , Medizin , Allgemeine Naturwissenschaft

Publiziert von National Academy of Sciences

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Configurational fingerprints of multicellular living systems (2021)

Yang, Haiqian ; Pegoraro, Adrian F. ; Han, Yulong ; [weitere]

National Academy of Sciences

In: PNAS - Proceedings of the National Academy of Sciences of the United States of America. 2021; 118(44): e2109168118. Published 2021 Oct 29. doi: 10.1073/pnas.2109168118.

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Publikationsdatum: 2021-10-29

Beschreibung: Cells cooperate as groups to achieve structure and function at the tissue level, during which specific material characteristics emerge. Analogous to phase transitions in classical physics, transformations in the material characteristics of multicellular assemblies are essential for a variety of vital processes including morphogenesis, wound healing, and cancer. In this work, we develop configurational fingerprints of particulate and multicellular assemblies and extract volumetric and shear order parameters based on this fingerprint to quantify the system disorder. Theoretically, these two parameters form a complete and unique pair of signatures for the structural disorder of a multicellular system. The evolution of these two order parameters offers a robust and experimentally accessible way to map the phase transitions in expanding cell monolayers and during embryogenesis and invasion of epithelial spheroids.

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Thema: Biologie , Medizin , Allgemeine Naturwissenschaft

Publiziert von National Academy of Sciences

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Demonstration of the role of cell wall homeostasis in Staphylococcus aureus growth and the action of bactericidal antibiotics (2021)

Salamaga, Bartłomiej ; Kong, Lingyuan ; Pasquina-Lemonche, Laia ; [weitere]

National Academy of Sciences

In: PNAS - Proceedings of the National Academy of Sciences of the United States of America. 2021; 118(44): e2106022118. Published 2021 Oct 29. doi: 10.1073/pnas.2106022118.

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Publikationsdatum: 2021-10-29

Beschreibung: Bacterial cell wall peptidoglycan is essential, maintaining both cellular integrity and morphology, in the face of internal turgor pressure. Peptidoglycan synthesis is important, as it is targeted by cell wall antibiotics, including methicillin and vancomycin. Here, we have used the major human pathogen Staphylococcus aureus to elucidate both the cell wall dynamic processes essential for growth (life) and the bactericidal effects of cell wall antibiotics (death) based on the principle of coordinated peptidoglycan synthesis and hydrolysis. The death of S. aureus due to depletion of the essential, two-component and positive regulatory system for peptidoglycan hydrolase activity (WalKR) is prevented by addition of otherwise bactericidal cell wall antibiotics, resulting in stasis. In contrast, cell wall antibiotics kill via the activity of peptidoglycan hydrolases in the absence of concomitant synthesis. Both methicillin and vancomycin treatment lead to the appearance of perforating holes throughout the cell wall due to peptidoglycan hydrolases. Methicillin alone also results in plasmolysis and misshapen septa with the involvement of the major peptidoglycan hydrolase Atl, a process that is inhibited by vancomycin. The bactericidal effect of vancomycin involves the peptidoglycan hydrolase SagB. In the presence of cell wall antibiotics, the inhibition of peptidoglycan hydrolase activity using the inhibitor complestatin results in reduced killing, while, conversely, the deregulation of hydrolase activity via loss of wall teichoic acids increases the death rate. For S. aureus, the independent regulation of cell wall synthesis and hydrolysis can lead to cell growth, death, or stasis, with implications for the development of new control regimes for this important pathogen.

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Thema: Biologie , Medizin , Allgemeine Naturwissenschaft

Publiziert von National Academy of Sciences

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SARS-CoV-2 evolution in animals suggests mechanisms for rapid variant selection (2021)

Bashor, Laura ; Gagne, Roderick B. ; Bosco-Lauth, Angela M. ; [weitere]

National Academy of Sciences

In: PNAS - Proceedings of the National Academy of Sciences of the United States of America. 2021; 118(44): e2105253118. Published 2021 Oct 29. doi: 10.1073/pnas.2105253118.

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Publikationsdatum: 2021-10-29

Beschreibung: SARS-CoV-2 spillback from humans into domestic and wild animals has been well documented, and an accumulating number of studies illustrate that human-to-animal transmission is widespread in cats, mink, deer, and other species. Experimental inoculations of cats, mink, and ferrets have perpetuated transmission cycles. We sequenced full genomes of Vero cell–expanded SARS-CoV-2 inoculum and viruses recovered from cats (n = 6), dogs (n = 3), hamsters (n = 3), and a ferret (n = 1) following experimental exposure. Five nonsynonymous changes relative to the USA-WA1/2020 prototype strain were near fixation in the stock used for inoculation but had reverted to wild-type sequences at these sites in dogs, cats, and hamsters within 1- to 3-d postexposure. A total of 14 emergent variants (six in nonstructural genes, six in spike, and one each in orf8 and nucleocapsid) were detected in viruses recovered from animals. This included substitutions in spike residues H69, N501, and D614, which also vary in human lineages of concern. Even though a live virus was not cultured from dogs, substitutions in replicase genes were detected in amplified sequences. The rapid selection of SARS-CoV-2 variants in vitro and in vivo reveals residues with functional significance during host switching. These observations also illustrate the potential for spillback from animal hosts to accelerate the evolution of new viral lineages, findings of particular concern for dogs and cats living in households with COVID-19 patients. More generally, this glimpse into viral host switching reveals the unrealized rapidity and plasticity of viral evolution in experimental animal model systems.

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Thema: Biologie , Medizin , Allgemeine Naturwissenschaft

Publiziert von National Academy of Sciences

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Fevers and the social costs of acute infection in wild vervet monkeys (2021)

McFarland, Richard ; Henzi, S. Peter ; Barrett, Louise ; [weitere]

National Academy of Sciences

In: PNAS - Proceedings of the National Academy of Sciences of the United States of America. 2021; 118(44): e2107881118. Published 2021 Oct 29. doi: 10.1073/pnas.2107881118.

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Publikationsdatum: 2021-10-29

Beschreibung: Fevers are considered an adaptive response by the host to infection. For gregarious animals, however, fever and the associated sickness behaviors may signal a temporary loss of capacity, offering other group members competitive opportunities. We implanted wild vervet monkeys (Chlorocebus pygerythrus) with miniature data loggers to obtain continuous measurements of core body temperature. We detected 128 fevers in 43 monkeys, totaling 776 fever-days over a 6-year period. Fevers were characterized by a persistent elevation in mean and minimum 24-h body temperature of at least 0.5 °C. Corresponding behavioral data indicated that febrile monkeys spent more time resting and less time feeding, consistent with the known sickness behaviors of lethargy and anorexia, respectively. We found no evidence that fevers influenced the time individuals spent socializing with conspecifics, suggesting social transmission of infection within a group is likely. Notably, febrile monkeys were targeted with twice as much aggression from their conspecifics and were six times more likely to become injured compared to afebrile monkeys. Our results suggest that sickness behavior, together with its agonistic consequences, can carry meaningful costs for highly gregarious mammals. The degree to which social factors modulate the welfare of infected animals is an important aspect to consider when attempting to understand the ecological implications of disease.

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Thema: Biologie , Medizin , Allgemeine Naturwissenschaft

Publiziert von National Academy of Sciences

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Accurate model of liquid–liquid phase behavior of intrinsically disordered proteins from optimization of single-chain properties (2021)

Tesei, Giulio ; Schulze, Thea K. ; Crehuet, Ramon ; [weitere]

National Academy of Sciences

In: PNAS - Proceedings of the National Academy of Sciences of the United States of America. 2021; 118(44): e2111696118. Published 2021 Oct 29. doi: 10.1073/pnas.2111696118.

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Publikationsdatum: 2021-10-29

Beschreibung: Many intrinsically disordered proteins (IDPs) may undergo liquid–liquid phase separation (LLPS) and participate in the formation of membraneless organelles in the cell, thereby contributing to the regulation and compartmentalization of intracellular biochemical reactions. The phase behavior of IDPs is sequence dependent, and its investigation through molecular simulations requires protein models that combine computational efficiency with an accurate description of intramolecular and intermolecular interactions. We developed a general coarse-grained model of IDPs, with residue-level detail, based on an extensive set of experimental data on single-chain properties. Ensemble-averaged experimental observables are predicted from molecular simulations, and a data-driven parameter-learning procedure is used to identify the residue-specific model parameters that minimize the discrepancy between predictions and experiments. The model accurately reproduces the experimentally observed conformational propensities of a set of IDPs. Through two-body as well as large-scale molecular simulations, we show that the optimization of the intramolecular interactions results in improved predictions of protein self-association and LLPS.

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Thema: Biologie , Medizin , Allgemeine Naturwissenschaft

Publiziert von National Academy of Sciences

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Live agent preference and social action monitoring in the macaque mid-superior temporal sulcus region (2021)

Ninomiya, Taihei ; Noritake, Atsushi ; Isoda, Masaki

National Academy of Sciences

In: PNAS - Proceedings of the National Academy of Sciences of the United States of America. 2021; 118(44): e2109653118. Published 2021 Oct 29. doi: 10.1073/pnas.2109653118.

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Publikationsdatum: 2021-10-29

Beschreibung: Mentalizing, the ability to infer the mental states of others, is a cornerstone of adaptive social intelligence. While functional brain mapping of human mentalizing has progressed considerably, its evolutionary signature in nonhuman primates remains debated. The discovery that the middle part of the macaque superior temporal sulcus (mid-STS) region has a connectional fingerprint most similar to the human temporoparietal junction (TPJ)—a crucial node in the mentalizing network—raises the possibility that these cortical areas may also share basic functional properties associated with mentalizing. Here, we show that this is the case in aspects of a preference for live social interactions and in a theoretical framework of predictive coding. Macaque monkeys were trained to perform a turn-taking choice task with another real monkey partner sitting directly face-to-face or a filmed partner appearing in prerecorded videos. We found that about three-fourths of task-related mid-STS neurons exhibited agent-dependent activity, most responding selectively or preferentially to the partner’s action. At the population level, activities of these partner-type neurons were significantly greater under live-partner compared to video-recorded–partner task conditions. Furthermore, a subset of the partner-type neurons responded proactively when predictions about the partner’s action were violated. This prediction error coding was specific to the action domain; almost none of the neurons signaled error in the prediction of reward. The present findings highlight unique roles of the macaque mid-STS at the single-neuron level and further delineate its functional parallels with the human TPJ in social cognitive processes associated with mentalizing.

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Thema: Biologie , Medizin , Allgemeine Naturwissenschaft

Publiziert von National Academy of Sciences

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MDM2, MDMX, and p73 regulate cell-cycle progression in the absence of wild-type p53 (2021)

Klein, Alyssa M. ; Biderman, Lynn ; Tong, David ; [weitere]

National Academy of Sciences

In: PNAS - Proceedings of the National Academy of Sciences of the United States of America. 2021; 118(44): e2102420118. Published 2021 Oct 29. doi: 10.1073/pnas.2102420118.

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Publikationsdatum: 2021-10-29

Beschreibung: The p53 tumor suppressor protein, known to be critically important in several processes including cell-cycle arrest and apoptosis, is highly regulated by multiple mechanisms, most certifiably the Murine Double Minute 2–Murine Double Minute X (MDM2–MDMX) heterodimer. The role of MDM2–MDMX in cell-cycle regulation through inhibition of p53 has been well established. Here we report that in cells either lacking p53 or expressing certain tumor-derived mutant forms of p53, loss of endogenous MDM2 or MDMX, or inhibition of E3 ligase activity of the heterocomplex, causes cell-cycle arrest. This arrest is correlated with a reduction in E2F1, E2F3, and p73 levels. Remarkably, direct ablation of endogenous p73 produces a similar effect on the cell cycle and the expression of certain E2F family members at both protein and messenger RNA levels. These data suggest that MDM2 and MDMX, working at least in part as a heterocomplex, may play a p53-independent role in maintaining cell-cycle progression by promoting the activity of E2F family members as well as p73, making them a potential target of interest in cancers lacking wild-type p53.

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Thema: Biologie , Medizin , Allgemeine Naturwissenschaft

Publiziert von National Academy of Sciences

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The middle cingulate cortex and dorso-central insula: A mirror circuit encoding observation and execution of vitality forms (2021)

Di Cesare, G. ; Marchi, M. ; Lombardi, G. ; [weitere]

National Academy of Sciences

In: PNAS - Proceedings of the National Academy of Sciences of the United States of America. 2021; 118(44): e2111358118. Published 2021 Oct 29. doi: 10.1073/pnas.2111358118.

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Publikationsdatum: 2021-10-29

Beschreibung: Actions with identical goals can be executed in different ways (gentle, rude, vigorous, etc.), which D. N. Stern called vitality forms [D. N. Stern, Forms of Vitality Exploring Dynamic Experience in Psychology, Arts, Psychotherapy, and Development (2010)]. Vitality forms express the agent’s attitudes toward others. In a series of fMRI studies, we found that the dorso-central insula (DCI) is the region that is selectively active during both vitality form observation and execution. In one previous experiment, however, the middle cingulate gyrus also exhibited activation. In the present study, in order to assess the role of the cingulate cortex in vitality form processing, we adopted a classical vitality form paradigm, but making the control condition devoid of vitality forms using jerky movements. Participants performed two different tasks: Observation of actions performed gently or rudely and execution of the same actions. The results showed that in addition to the insula, the middle cingulate cortex (MCC) was strongly activated during both action observation and execution. Using a voxel-based analysis, voxels showing a similar trend of the blood-oxygen-level-dependent (BOLD) signal in both action observation and execution were found in the DCI and in the MCC. Finally, using a multifiber tractography analysis, we showed that the active sites in MCC and DCI are reciprocally connected.

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Thema: Biologie , Medizin , Allgemeine Naturwissenschaft

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