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Pigs have played a significant role in biological and medical research for many years. In the case of non-rodent models, pigs are the primary choices as experimental animals in the cardiovascular studies. Accumulating data indicate that the closed-chest coronary balloon-occlusion technique is one of the most successful method for creating ischemic heart failure (HF). However, consistent and thoroughly characterized large animal models of HF are a critical translational tool for drug development and toxicology. The knowledge of the different catheterization protocols is crucial to ensure a suitable animal model which can serve as a human-related preclinical validation process. Therefore it is essential to follow an optimized and standardized experimental protocol on a homogenous animal population, which help to obtain reliable and useful data for the translational large animal research programs. [ABSTRACT FROM AUTHOR]

The biomedical research infrastructure of our academic medical centers elucidates disease mechanisms and develops diagnostic tests and treatments with scientific rigor, but the mechanism for reliably moving these findings into clinical settings lacks careful design. Hence, there is a wide gap between medical discoveries and the health benefit realized by the U.S. population. Performance improvement (PI) is a discipline that focuses on intentional redesign of core processes in our health system to close these gaps. The application of PI science is more consequential to health outcomes as is traditional biomedical research. This article describes why application and recognition of PI science as a discipline is imperative and why we should require training with similar intensity in undergraduate medical education (UME) and graduate medical education (GME). It also proposes investment in infrastructure (developing faculty expertise) and rigorous fellowships, which are, perhaps, more likely to thrive in teaching hospitals with a strong clinical mission. [ABSTRACT FROM AUTHOR]

The morphometrics of fish otoliths have been commonly used to investigate population structures and the environmental impacts on ontogeny. These studies can require hundreds if not thousands of otoliths to be collected and processed. Processing these otoliths takes up valuable time, money, and resources that can be saved by automation. These structures also contain relevant information in three dimensions that is lost with 2D morphometric methods from photographic analysis. In this study, the otoliths of three populations of coho salmon (Oncorhynchus kisutch) were examined with manual 2D, automated 2D, and automated 3D otolith measurement methods. The automated 3D method was able to detect an 8% difference in average otolith density, while 2D methods could not. Due to the loss of information in the z axis, and the longer processing time, 2D methods can take up to 100 times longer to reach the same statistical power as automated 3D methods. Automated 3D methods are faster, can answer a wider range of questions, and allow fisheries scientists to automate rather monotonous tasks. La morphometrie des otolites de poissons a souvent ete utilisee pour etudier les structures de populations et les impacts de l'environnement sur l'ontogenese. Ces etudes peuvent necessiter le prelevement et le traitement de centaines, voire de milliers d'otolites. Le traitement de ces otolites prend du temps, de l'argent et des ressources precieuses que l'automatisation peut permettre d'epargner. Ces structures contiennent egalement de l'information tridimensionnelle interessante que l'utilisation de methodes morphometriques basees sur l'analyse de photographies evacue. Dans la presente etude, les otolites de trois populations de saumons cohos (Oncorhynchus kisutch) ont ete examines par des methodes de mesure des otolites en 2D manuelle, en 2D automatisee et en 3D automatisee. Cette derniere methode a pu detecter une difference de 8 % de la densite moyenne des otolites, ce que les methodes 2D n'ont pu faire. En raison de la perte d'information le long de l'axe z et du temps de traitement plus long, les methodes 2D peuvent prendre jusqu'a 100 fois plus longtemps pour atteindre la meme efficacite statistique que des methodes 3D automatisees. Ces dernieres sont plus rapides, permettent de repondre a un plus grand eventail de questions et permettent aux specialistes des sciences halieutiques d'automatiser des taches plutot monotones. [Traduit par la Redaction], Introduction Morphometrics is the study of the variation of size and shape. While biologists have used morphometrics for centuries, the use of quantitative morphometrics of structures within organisms is more [...]

This review describes an Indigenous-led project run by Q'eqchi' Maya Healers of Belize meant to strengthen and improve traditional botanical healing. The goals of this project were to conserve medicinal plant knowledge by way of ethnobotanical studies, and to conserve the plants themselves by creating a community ethnobotanical garden. A total of 169 medicinal species were collected in the ethnobotanical survey, which provided unique knowledge on many rainforest species of the wet lowland forest of southern Belize, not found in neighbouring Indigenous cultures. Consensus on plant uses by the Healers was high, indicating a well-conserved, codified oral history. After horticultural experimentation by the Healers, the Indigenous botanical garden provided a habitat for and conservation of 102 medicinal species including many epiphytes that were rescued from forested areas. Ethnopharmacological studies by the university partners showed a pharmacological basis for, and active principles of, plants used for epilepsy and anxiety, for inflammatory conditions such as arthritis, for dermatological mycoses, and for type 2 diabetes complications. Overall, the project has provided a model for Indigenous empowerment and First Nation's science, as well as establishing traditional medicine as an important, unified healing practice that can safely and effectively provide primary health care in its cultural context. Key words: ethnobotany, ethnopharmacology, Q'eqchi' Maya, Mesoamerican flora, Belize. Cette revue décrit un projet mené par des guérisseurs mayas Q'eqchi' de Xna'ajeb' aj Ralch'o'och' (Belize) pour renforcer et améliorer la médecine botanique traditionnelle. Les objectifs du projet étaient de conserver les connaissances sur les plantes médicinales, ce qui a conduit à des études ethnobotaniques, et de conserver les plantes elles-mêmes, en créant un jardin ethnobotanique dirigé par la communauté. Au total, 169 espèces médicinales ont été collectées dans le cadre de l'ethnobotanique, ce qui a permis d'acquérir des connaissances uniques sur de nombreuses espèces de la forêt pluviale des basses terres humides du sud du Belize, que l'on ne trouve pas dans les cultures indigènes voisines. Le consensus sur l'utilisation des plantes par les guérisseurs était élevé, ce qui indique une histoire orale codifiée bien conservée. Après l'expérimentation horticole des guérisseurs, le jardin botanique indigène a permis d'abriter et de conserver 102 espèces médicinales, dont de nombreux épiphytes provenant de zones forestières. Des études ethnopharmacologiques menées par les partenaires universitaires ont mis en évidence la base pharmacologique et les principes actifs de plantes utilisées pour traiter l'épilepsie et l'anxiété, les états inflammatoires tels que l'arthrite, les mycoses dermatologiques et les complications du diabète de type 2. Dans l'ensemble, le projet a fourni un modèle pour l'autonomisation des autochtones et la science des Premières nations, tout en établissant cette médecine traditionnelle comme une pratique de guérison importante et unifiée, qui peut fournir en toute sécurité et efficacement des soins de santé primaires dans son contexte culturel. Mots-clés : ethnobotanique, ethnopharmacologie, Mayas Q'eqchi', flore mésoaméricaine, Belize., B'antyox re loq'lajChoxaa ut li loqlajCh'och' jo'kanajwi' naqab'antyoxireheb' li qasqitz'inhaneb' xmuhileb' wankchikcho'oqIq', ha', kutanitch'o'ocheb' chikhaneb'eb chikajK'amalb'eheb' re qachab'iltyuham... Thanks to the Hearth of Heaven and Hearth of Earth and to [...]

The Asteraceae is the largest family of plants in North America and is widely used as medicine by Indigenous peoples. This study investigated the medicinal ethnobotany of North American Asteraceae to identify taxa that appear preferentially selected or avoided for general and specific medicinal uses. Asteraceae-specific ethnobotanical reports recorded in the Native American Ethnobotany database were compiled and, using residual and binomial analyses, 14 tribes were compared and ranked as either over- or under-selected for medicine, food, or technology, and for different categories of medicinal applications. Statistical analysis supported the hypothesis that the selection of species for ethnobotanical purposes is non-random and does not depend on the size of the flora. The Anthemideae tribe was identified as over-selected for all types of applications, including most therapeutic categories, most significantly as pulmonary and orthopedic aids. Subsequent analysis revealed that the over-representation of this tribe was attributed mainly to Achillea millefolium L. and Artemisia spp. The significance of Anthemideae, particularly of Achillea and Artemisia species as highly selected medicinal taxa, emphasizes their cultural importance to Indigenous North Americans. Residual and binomial statistics generally provided parallel results, but supplementary statistical methods, further in-depth investigation of other use categories, and inclusion of plant distribution data may provide greater insight into traditional uses of Asteraceae in North America. Key words: ethnobotany, herbal medicine, Compositae, plant diversity, Anthemideae, Achillea millefolium L., Artemisia. Les astéracées constituent la plus grande famille de plantes en Amérique du Nord et sont largement utilisées comme médicaments par les peuples autochtones. Cette étude a examiné l'ethnobotanique médicinale des astéracées d'Amérique du Nord afin d'identifier les taxons qui semblent préférentiellement sélectionnés ou évités pour des usages médicinaux généraux et spécifiques. Les rapports ethnobotaniques spécifiques aux astéracées enregistrés dans la base de données <> ont été compilés et, à l'aide d'analyses résiduelles et binomiales, 14 tribus ont été comparées et classées comme sur- ou sous-sélectionnées en médecine, en alimentation ou en technologie, et pour différentes catégories d'applications médicinales. L'analyse statistique a confirmé l'hypothèse selon laquelle la sélection des espèces à des fins ethnobotaniques n'est pas aléatoire et ne dépend pas de la taille de la flore. La tribu des Anthemideae a été identifiée comme étant sursélectionnée dans tous les types d'applications, y compris la plupart des catégories thérapeutiques, et plus particulièrement comme aides pulmonaires et orthopédiques. Une analyse subséquente a révélé que la surreprésentation de cette tribu était attribuée principalement à Achillea millefolium L. et à Artemisia spp. L'importance des Anthemideae, en particulier des espèces Achillea et Artemisia, en tant que taxons médicinaux hautement sélectionnés, souligne leur importance culturelle pour les Autochtones nord-américains. Les statistiques résiduelles et binomiales ont généralement fourni des résultats parallèles, mais des méthodes statistiques supplémentaires, une étude plus approfondie d'autres catégories d'utilisation et l'inclusion de données sur la distribution des plantes pourraient permettre de mieux comprendre les utilisations traditionnelles des astér-acées en Amérique du Nord. [Traduit par la Rédaction] Mots-clés : ethnobotanique, phytothérapie, Compositae, diversité des plantes, Anthemideae, Achillea millefolium L., Artemisia., Introduction The Asteraceae (Compositae) is the largest family of flowering plants in North America. In addition to its diversity, the Asteraceae is also the most medicinally used family among Indigenous [...]

Big data is a term that refers to a set of data that, due to its largeness or complexity, cannot be stored or processed with one of the usual tools or applications for data management, and it has become a prominent word in recent years for the massive development of technology. Almost immediately thereafter, the term "big data mining" emerged, i.e., mining from big data even as an emerging and interconnected field of research. Classification is an important stage in data mining since it helps people make better decisions in a variety of situations, including scientific endeavors, biomedical research, and industrial applications. The probabilistic neural network (PNN) is a commonly used and successful method for handling classification and pattern recognition issues. In this study, the authors proposed to combine the probabilistic neural network (PPN), which is one of the data mining techniques, with the vibrating particles system (VPS), which is one of the metaheuristic algorithms named "VPS-PNN", to solve classification problems more effectively. The data set is eleven common benchmark medical datasets from the machine-learning library, the suggested method was tested. The suggested VPS-PNN mechanism outperforms the PNN, biogeography-based optimization, enhanced-water cycle algorithm (E-WCA) and the firefly algorithm (FA) in terms of convergence speed and classification accuracy. [ABSTRACT FROM AUTHOR]

The input of chemical and physical sciences to life sciences is increasingly important. Surface science as a complex multidisciplinary research area provides many relevant practical tools to support research in medicine. The tensiometry and surface rheology of human biological liquids as diagnostic tools have been very successfully applied. Additionally, for the characterization of pulmonary surfactants, this methodology is essential to deepen the insights into the functionality of the lungs and for the most efficient administration of certain drugs. Problems in ophthalmology can be addressed using surface science methods, such as the stability of the wetting films and the development of artificial tears. The serious problem of obesity is fast-developing in many industrial countries and must be better understood, while therapies for its treatment must also be developed. Finally, the application of fullerenes as a suitable system for detecting cancer in humans is discussed. [ABSTRACT FROM AUTHOR]

Quantitative phase imaging (QPI) has emerged as a valuable tool for biomedical research thanks to its unique capabilities for quantifying optical thickness variation of living cells and tissues. Among many QPI methods, Fourier ptychographic microscopy (FPM) allows long-term label-free observation and quantitative analysis of large cell populations without compromising spatial and temporal resolution. However, high spatio-temporal resolution imaging over a long-time scale (from hours to days) remains a critical challenge: optically inhomogeneous structure of biological specimens as well as mechanical perturbations and thermal fluctuations of the microscope body all result in time-varying aberration and focus drifts, significantly degrading the imaging performance for long-term study. Moreover, the aberrations are sample- and environment-dependent, and cannot be compensated by a fixed optical design, thus necessitating rapid dynamic correction in the imaging process. Here, we report an adaptive optical QPI method based on annular illumination FPM. In this method, the annular matched illumination configuration (i.e., the illumination numerical aperture (NA) strictly equals to the objective NA), which is the key for recovering low-frequency phase information, is further utilized for the accurate imaging aberration characterization. By using only 6 low-resolution images captured with 6 different illumination angles matching the NA of a 10x, 0.4 NA objective, we recover high-resolution quantitative phase images (synthetic NA of 0.8) and characterize the aberrations in real time, restoring the optimum resolution of the system adaptively. Applying our method to live-cell imaging, we achieve diffraction-limited performance (full-pitch resolution of 655 n m at a wavelength of 525 n m ) across a wide field of view ( 1.77 m m 2 ) over an extended period of time. [ABSTRACT FROM AUTHOR]

This paper presents a highly compact volume 12 mm3 Zig Zag-shaped implantable antenna for biomedical applications. The antenna performance is closely analyzed in terms of penetration depth, different human tissues, substrate materials, reflection coefficient, Impedance Bandwidth, directive gain, and SAR values. The three different models are analyzed for different resonating frequencies. It is found that the proposed antenna shows dual ISM bands (900 MHz to 970 MHz 2.36GHz to 2.49 GHz) with impedance bandwidth of 7.77 % and 5.5% respectively. The proposed implantable antenna is successfully fabricated and tested in skin mimicking gel (vitro model). The performance of the proposed antenna is enhanced by using a sorting pin and slots that provides dual ISM bands, an acceptable SAR of 856.3 W/KG, and a directive gain of -28.68 dBi. Parametric analysis of the proposed implantable antenna has been studied in detail. Simulated and fabricated results are compared and found almost similar. [ABSTRACT FROM AUTHOR]

Author(s): A. Hosseinizadeh [sup.1] , N. Breckwoldt [sup.2] [sup.3] [sup.4] , R. Fung [sup.1] , R. Sepehr [sup.1] , M. Schmidt [sup.1] , P. Schwander [sup.1] , R. Santra [sup.2] [...], The structural dynamics of a molecule are determined by the underlying potential energy landscape. Conical intersections are funnels connecting otherwise separate potential energy surfaces. Posited almost a century ago.sup.1, conical intersections remain the subject of intense scientific interest.sup.2-5. In biology, they have a pivotal role in vision, photosynthesis and DNA stability.sup.6. Accurate theoretical methods for examining conical intersections are at present limited to small molecules. Experimental investigations are challenged by the required time resolution and sensitivity. Current structure-dynamical understanding of conical intersections is thus limited to simple molecules with around ten atoms, on timescales of about 100 fs or longer.sup.7. Spectroscopy can achieve better time resolutions.sup.8, but provides indirect structural information. Here we present few-femtosecond, atomic-resolution videos of photoactive yellow protein, a 2,000-atom protein, passing through a conical intersection. These videos, extracted from experimental data by machine learning, reveal the dynamical trajectories of de-excitation via a conical intersection, yield the key parameters of the conical intersection controlling the de-excitation process and elucidate the topography of the electronic potential energy surfaces involved. Serial femtosecond crystallography (SFX) has provided significant understanding of time-resolved processes of various systems in biology, for example, rhodopsin, which underlies our vision. The approach involves femtosecond-length X-ray pulses directed at protein crystals and has been used to study various photoactive proteins. However, the function of proteins such as rhodopsin requires trans-cis isomerization of a chromophore, which involves crossing of a conical intersection--a funnel separating potential energy surfaces--at timescales faster than what can be achieved experimentally. Here, Ourmazd and colleagues report a machine learning analysis of SFX data of photoactive yellow protein, which resolves the protein passing through a conical intersection, providing information about the potential energy surfaces involved and achieving time resolution of less than 10 fs. This approach offers an opportunity to understand some of the fastest processes in biology by extracting even more information from SFX datasets.

Author(s): Jonnathan Singh Alvarado [sup.1] , Jack Goffinet [sup.2] , Valerie Michael [sup.1] , William Liberti III [sup.3] , Jordan Hatfield [sup.1] , Timothy Gardner [sup.4] , John Pearson [sup.1] [...], Musical and athletic skills are learned and maintained through intensive practice to enable precise and reliable performance for an audience. Consequently, understanding such complex behaviours requires insight into how the brain functions during both practice and performance. Male zebra finches learn to produce courtship songs that are more varied when alone and more stereotyped in the presence of females.sup.1. These differences are thought to reflect song practice and performance, respectively.sup.2,3, providing a useful system in which to explore how neurons encode and regulate motor variability in these two states. Here we show that calcium signals in ensembles of spiny neurons (SNs) in the basal ganglia are highly variable relative to their cortical afferents during song practice. By contrast, SN calcium signals are strongly suppressed during female-directed performance, and optogenetically suppressing SNs during practice strongly reduces vocal variability. Unsupervised learning methods.sup.4,5 show that specific SN activity patterns map onto distinct song practice variants. Finally, we establish that noradrenergic signalling reduces vocal variability by directly suppressing SN activity. Thus, SN ensembles encode and drive vocal exploration during practice, and the noradrenergic suppression of SN activity promotes stereotyped and precise song performance for an audience. In male zebra finches, song practice and courtship song performance are associated with distinct patterns of neural activity in the basal ganglia, resulting in reduced vocal variability during performance.

Author(s): Baihao Zhang [sup.1] , Alexis Vogelzang [sup.1] , Michio Miyajima [sup.1] , Yuki Sugiura [sup.2] , Yibo Wu [sup.3] , Kenji Chamoto [sup.4] , Rei Nakano [sup.5] , Ryusuke [...], Small, soluble metabolites not only are essential intermediates in intracellular biochemical processes, but can also influence neighbouring cells when released into the extracellular milieu.sup.1-3. Here we identify the metabolite and neurotransmitter GABA as a candidate signalling molecule synthesized and secreted by activated B cells and plasma cells. We show that B cell-derived GABA promotes monocyte differentiation into anti-inflammatory macrophages that secrete interleukin-10 and inhibit CD8.sup.+ T cell killer function. In mice, B cell deficiency or B cell-specific inactivation of the GABA-generating enzyme GAD67 enhances anti-tumour responses. Our study reveals that, in addition to cytokines and membrane proteins, small metabolites derived from B-lineage cells have immunoregulatory functions, which may be pharmaceutical targets allowing fine-tuning of immune responses. A paper in Nature demonstrates that B cell-derived GABA promotes monocyte differentiation into anti-inflammatory macrophages able to limit anti-tumour T cell cytotoxicity.

Author(s): Hongtao Zhu [sup.1] , Eric Gouaux [sup.1] [sup.2] Author Affiliations: (1) Vollum Institute, Oregon Health and Science University, Portland, USA (2) Howard Hughes Medical Institute, Oregon Health and Science [...], Glycine receptors (GlyRs) are pentameric, &apos;Cys-loop&apos; receptors that form chloride-permeable channels and mediate fast inhibitory signalling throughout the central nervous system.sup.1,2. In the spinal cord and brainstem, GlyRs regulate locomotion and cause movement disorders when mutated.sup.2,3. However, the stoichiometry of native GlyRs and the mechanism by which they are assembled remain unclear, despite extensive investigation.sup.4-8. Here we report cryo-electron microscopy structures of native GlyRs from pig spinal cord and brainstem, revealing structural insights into heteromeric receptors and their predominant subunit stoichiometry of 4[alpha]:1[beta]. Within the heteromeric pentamer, the [beta](+)-[alpha](-) interface adopts a structure that is distinct from the [alpha](+)-[alpha](-) and [alpha](+)-[beta](-) interfaces. Furthermore, the [beta]-subunit contains a unique phenylalanine residue that resides within the pore and disrupts the canonical picrotoxin site. These results explain why inclusion of the [beta]-subunit breaks receptor symmetry and alters ion channel pharmacology. We also find incomplete receptor complexes and, by elucidating their structures, reveal the architectures of partially assembled [alpha]-trimers and [alpha]-tetramers. Cryo-electron microscopy structures of pig glycine receptors indicate that they are predominantly assembled with 4[alpha]:1[beta] stoichiometry via [alpha]-homotrimer and homotetramer intermediates.

Author(s): Alfonso Ferrández-Roldán [sup.1] [sup.2] , Marc Fabregà-Torrus [sup.1] [sup.2] , Gaspar Sánchez-Serna [sup.1] [sup.2] , Enya Duran-Bello [sup.1] [sup.2] , Martí Joaqui[combining acute accent]n-Llui[combining acute accent]s [sup.1] [sup.2] , [...], A central question in chordate evolution is the origin of sessility in adult ascidians, and whether the appendicularian complete free-living style represents a primitive or derived condition among tunicates.sup.1. According to the &apos;a new heart for a new head&apos; hypothesis, the evolution of the cardiopharyngeal gene regulatory network appears as a pivotal aspect to understand the evolution of the lifestyles of chordates.sup.2-4. Here we show that appendicularians experienced massive ancestral losses of cardiopharyngeal genes and subfunctions, leading to the &apos;deconstruction&apos; of two ancestral modules of the tunicate cardiopharyngeal gene regulatory network. In ascidians, these modules are related to early and late multipotency, which is involved in lineage cell-fate determination towards the first and second heart fields and siphon muscles. Our work shows that the deconstruction of the cardiopharyngeal gene regulatory network involved the regressive loss of the siphon muscle, supporting an evolutionary scenario in which ancestral tunicates had a sessile ascidian-like adult lifestyle. In agreement with this scenario, our findings also suggest that this deconstruction contributed to the acceleration of cardiogenesis and the redesign of the heart into an open-wide laminar structure in appendicularians as evolutionary adaptations during their transition to a complete pelagic free-living style upon the innovation of the food-filtering house.sup.5. The heart of appendicularians has evolved by &apos;deconstructing&apos; an ancestral ascidian-like gene regulatory network.

Author(s): Shunsuke F. Shimobayashi [sup.1] , Pierre Ronceray [sup.2] [sup.3] , David W. Sanders [sup.1] , Mikko P. Haataja [sup.4] [sup.5] , Clifford P. Brangwynne [sup.1] [sup.5] [sup.6] Author Affiliations: [...], All structures within living cells must form at the right time and place. This includes condensates such as the nucleolus, Cajal bodies and stress granules, which form via liquid-liquid phase separation of biomolecules, particularly proteins enriched in intrinsically disordered regions (IDRs).sup.1,2. In non-living systems, the initial stages of nucleated phase separation arise when thermal fluctuations overcome an energy barrier due to surface tension. This phenomenon can be modelled by classical nucleation theory (CNT), which describes how the rate of droplet nucleation depends on the degree of supersaturation, whereas the location at which droplets appear is controlled by interfacial heterogeneities.sup.3,4. However, it remains unknown whether this framework applies in living cells, owing to the multicomponent and highly complex nature of the intracellular environment, including the presence of diverse IDRs, whose specificity of biomolecular interactions is unclear.sup.5-8. Here we show that despite this complexity, nucleation in living cells occurs through a physical process similar to that in inanimate materials, but the efficacy of nucleation sites can be tuned by their biomolecular features. By quantitatively characterizing the nucleation kinetics of endogenous and biomimetic condensates in living cells, we find that key features of condensate nucleation can be quantitatively understood through a CNT-like theoretical framework. Nucleation rates can be substantially enhanced by compatible biomolecular (IDR) seeds, and the kinetics of cellular processes can impact condensate nucleation rates and specificity of location. This quantitative framework sheds light on the intracellular nucleation landscape, and paves the way for engineering synthetic condensates precisely positioned in space and time. Experiments using endogenous and biomimetic condensates in cells show that nucleation in cells resembles the physical process in inanimate materials, but is tuned by biomolecular features.

Author(s): Mikihito Shibata [sup.1] , Kartik Pattabiraman [sup.1] [sup.2] , Belen Lorente-Galdos [sup.1] , David Andrijevic [sup.1] , Suel-Kee Kim [sup.1] , Navjot Kaur [sup.1] , Sydney K. Muchnik [sup.1] [...], The prefrontal cortex (PFC) and its connections with the mediodorsal thalamus are crucial for cognitive flexibility and working memory.sup.1 and are thought to be altered in disorders such as autism.sup.2,3 and schizophrenia.sup.4,5. Although developmental mechanisms that govern the regional patterning of the cerebral cortex have been characterized in rodents.sup.6-9, the mechanisms that underlie the development of PFC-mediodorsal thalamus connectivity and the lateral expansion of the PFC with a distinct granular layer 4 in primates.sup.10,11 remain unknown. Here we report an anterior (frontal) to posterior (temporal), PFC-enriched gradient of retinoic acid, a signalling molecule that regulates neural development and function.sup.12-15, and we identify genes that are regulated by retinoic acid in the neocortex of humans and macaques at the early and middle stages of fetal development. We observed several potential sources of retinoic acid, including the expression and cortical expansion of retinoic-acid-synthesizing enzymes specifically in primates as compared to mice. Furthermore, retinoic acid signalling is largely confined to the prospective PFC by CYP26B1, a retinoic-acid-catabolizing enzyme, which is upregulated in the prospective motor cortex. Genetic deletions in mice revealed that retinoic acid signalling through the retinoic acid receptors RXRG and RARB, as well as CYP26B1-dependent catabolism, are involved in proper molecular patterning of prefrontal and motor areas, development of PFC-mediodorsal thalamus connectivity, intra-PFC dendritic spinogenesis and expression of the layer 4 marker RORB. Together, these findings show that retinoic acid signalling has a critical role in the development of the PFC and, potentially, in its evolutionary expansion. Studies in mice, humans and macaques show that retinoic acid signalling has an important role in the development of the prefrontal cortex (PFC) in primates and may also underlie the evolutionary diversification of the PFC.

Author(s): Alice S. French [sup.1] , Quentin Geissmann [sup.2] , Esteban J. Beckwith [sup.3] , Giorgio F. Gilestro [sup.1] Author Affiliations: (1) Department of Life Sciences, Imperial College London, London, [...], During sleep, most animal species enter a state of reduced consciousness characterized by a marked sensory disconnect. Yet some processing of the external world must remain intact, given that a sleeping animal can be awoken by intense stimuli (for example, a loud noise or a bright light) or by soft but qualitatively salient stimuli (for example, the sound of a baby cooing or hearing one&apos;s own name.sup.1-3). How does a sleeping brain retain the ability to process the quality of sensory information? Here we present a paradigm to study the functional underpinnings of sensory discrimination during sleep in Drosophila melanogaster. We show that sleeping vinegar flies, like humans, discern the quality of sensory stimuli and are more likely to wake up in response to salient stimuli. We also show that the salience of a stimulus during sleep can be modulated by internal states. We offer a prototypical blueprint detailing a circuit involved in this process and its modulation as evidence that the system can be used to explore the cellular underpinnings of how a sleeping brain experiences the world. The authors develop a paradigm to study sensory discrimination during sleep in Drosophila melanogaster.

Author(s): Jason Y. Lee [sup.1] , Heechul Jun [sup.1] , Shogo Soma [sup.1] [sup.3] , Tomoaki Nakazono [sup.1] [sup.4] , Kaori Shiraiwa [sup.1] , Ananya Dasgupta [sup.1] , Tatsuki Nakagawa [...], Mounting evidence shows that dopamine in the striatum is critically involved in reward-based reinforcement learning.sup.1,2. However, it remains unclear how dopamine reward signals influence the entorhinal-hippocampal circuit, another brain network that is crucial for learning and memory.sup.3-5. Here, using cell-type-specific electrophysiological recording.sup.6, we show that dopamine signals from the ventral tegmental area and substantia nigra control the encoding of cue-reward association rules in layer 2a fan cells of the lateral entorhinal cortex (LEC). When mice learned novel olfactory cue-reward associations using a pre-learned association rule, spike representations of LEC fan cells grouped newly learned rewarded cues with a pre-learned rewarded cue, but separated them from a pre-learned unrewarded cue. Optogenetic inhibition of fan cells impaired the learning of new associations while sparing the retrieval of pre-learned memory. Using fibre photometry, we found that dopamine sends novelty-induced reward expectation signals to the LEC. Inhibition of LEC dopamine signals disrupted the associative encoding of fan cells and impaired learning performance. These results suggest that LEC fan cells represent a cognitive map of abstract task rules, and that LEC dopamine facilitates the incorporation of new memories into this map. Cell-type-specific electrophysiological recording, fibre photometry and optogenetic manipulations in mice show that dopamine signals from the ventral tegmental area to the lateral entorhinal cortex have a key role in cue-reward associative learning.

The article is devoted to the work of the Moscow Research Institute of Psychiatry to improve psychiatric care for patients with psychotic disorders. An important feature of this work was an integrated approach, in which the clinical picture of the disease was assessed in close connection with the patient's personal and psychological characteristics, social conditions of his life, therapeutic opportunities, rehabilitation potential and organizational structure of care. The article reflects the results of many years of work of the department of outpatient psychiatry and the organization of psychiatric care under the guidance of Professor I.Ya. Gurovich. The results of scientific research carried out by the staff of the institute in a traditional humanistic manner are presented. The translational nature of the research is emphasized by its inextricable link with clinical and social approaches. As a result of many years of work, a concept was developed to provide assistance to various groups of patients, starting with the first manifestations of the disease and ending with cases of long-term chronic disorders with a pronounced level of social maladaptation. As a result, a whole spectrum of new organizational forms of psychiatric care was proposed, such as departments (clinics) of the first psychotic episode, medical rehabilitation departments, assertive community treatment departments, designed for the most difficult patients. These organizational forms were fixed in the regulatory documents of the Ministry of Health and Social Development of the Russian Federation. To date, the above departments have been established in psychiatric institutions in many regions of the Russian Federation. Further development of this area is associated with neurobiological research to identify complex biomarkers of psychotic spectrum disorders. Thus, the research carried out at the present time preserves the tradition of an integrated clinical and social approach to the study of mental disorders. It is shown that an important advantage of this approach is their translational nature.