Dual Origin Research Articles

ILC WORK ON THE CODIFICATION OF GENERAL LEGAL PRINCIPLES

The codification of sources of international law is a monolith and lengthy project. After many decades of codifying international treaty law and international customary law, the International Law Commission has finally decided to tackle the topic of General principles of law as late as 2018. The codification of general legal principles is challenging for many reasons: the unclear or ambiguous practice of states and international justice, lack of unity of opinion in the doctrine, and terminological inconsistency. However, in the current debate within the International Law Commission, the most controversial issue is the idea of the “two-category” approach which entails their dual origin. Namely, they can be derived not only from national legal systems but also from the international legal order itself. The paper provides an overview of the work of the International Law Commission accomplished so far, with the aim to shed light on certain aspects of the proposed course of action.

Neural crest cell-placodal neuron interactions are mediated by Cadherin-7 and N-cadherin during early chick trigeminal ganglion assembly

Background: Arising at distinct positions in the head, the cranial ganglia are crucial for integrating various sensory inputs. The largest of these ganglia is the trigeminal ganglion, which relays pain, touch and temperature information through its three primary nerve branches to the central nervous system. The trigeminal ganglion and its nerves are composed of derivatives of two critical embryonic cell types, neural crest cells and placode cells, that migrate from different anatomical locations, coalesce together, and differentiate to form trigeminal sensory neurons and supporting glia. While the dual cellular origin of the trigeminal ganglion has been known for over 60 years, molecules expressed by neural crest cells and placode cells that regulate initial ganglion assembly remain obscure. Prior studies revealed the importance of cell surface cadherin proteins during early trigeminal gangliogenesis, with Cadherin-7 and neural cadherin (N-cadherin) expressed in neural crest cells and placode cells, respectively. Although cadherins typically interact in a homophilic ( i.e., like) fashion, the presence of different cadherins on these intermingling cell populations raises the question as to whether heterophilic cadherin interactions may also be occurring during initial trigeminal ganglion formation, which was the aim of this study. Methods: To assess potential interactions between Cadherin-7 and N-cadherin, we used biochemistry and innovative imaging assays conducted in vitro and in vivo, including in the forming chick trigeminal ganglion. Results: Our data revealed a physical interaction between Cadherin-7 and N-cadherin. Conclusions: These studies identify a new molecular basis by which neural crest cells and placode cells can aggregate in vivo to build the trigeminal ganglion during embryogenesis.

Protein folds as synapomorphies of the tree of life.

Several studies showed that folds (topology of protein secondary structures) distribution in proteomes may be a global proxy to build phylogeny. Then, some folds should be synapomorphies (derived characters exclusively shared among taxa). However, previous studies used methods that did not allow synapomorphy identification, which requires congruence analysis of folds as individual characters. Here, we map SCOP folds onto a sample of 210 species across the tree of life (TOL). Congruence is assessed using retention index of each fold for the TOL, and principal component analysis for deeper branches. Using a bicluster mapping approach, we define synapomorphic blocks of folds (SBF) sharing similar presence/absence patterns. Among the 1232 folds, 20% are universally present in our TOL, whereas 54% are reliable synapomorphies. These results are similar with CATH and ECOD databases. Eukaryotes are characterized by a large number of them, and several SBFs clearly support nested eukaryotic clades (divergence times from 1100 to 380 mya). Although clearly separated, the three superkingdoms reveal a strong mosaic pattern. This pattern is consistent with the dual origin of eukaryotes and witness secondary endosymbiosis in their phothosynthetic clades. Our study unveils direct analysis of folds synapomorphies as key characters to unravel evolutionary history of species.

Neural crest cell-placodal neuron interactions are mediated by Cadherin-7 and N-cadherin during early chick trigeminal ganglion assembly.

Background: Arising at distinct positions in the head, the cranial ganglia are crucial for integrating various sensory inputs. The largest of these ganglia is the trigeminal ganglion, which relays pain, touch and temperature information through its three primary nerve branches to the central nervous system. The trigeminal ganglion and its nerves are composed of derivatives of two critical embryonic cell types, neural crest cells and placode cells, that migrate from different anatomical locations, coalesce together, and differentiate to form trigeminal sensory neurons and supporting glia. While the dual cellular origin of the trigeminal ganglion has been known for over 60 years, molecules expressed by neural crest cells and placode cells that regulate initial ganglion assembly remain obscure. Prior studies revealed the importance of cell surface cadherin proteins during early trigeminal gangliogenesis, with Cadherin-7 and neural cadherin (N-cadherin) expressed in neural crest cells and placode cells, respectively. Although cadherins typically interact in a homophilic ( i.e., like) fashion, the presence of different cadherins on these intermingling cell populations raises the question as to whether heterophilic cadherin interactions may also be occurring during initial trigeminal ganglion formation, which was the aim of this study. Methods: To assess potential interactions between Cadherin-7 and N-cadherin, we used biochemistry and innovative imaging assays conducted in vitro and in vivo, including in the forming chick trigeminal ganglion. Results: Our data revealed a physical interaction between Cadherin-7 and N-cadherin. Conclusions: These studies identify a new molecular basis by which neural crest cells and placode cells can aggregate in vivo to build the trigeminal ganglion during embryogenesis.

Genetic tracing reveals transcription factor Foxp3-dependent and Foxp3-independent functionality of peripherally induced Treg cells

Regulatory T (Treg) cells expressing the transcription factor Foxp3 are an essential suppressive Tcell lineage of dual origin: Foxp3 induction in thymocytes and mature CD4+ Tcells gives rise to thymic (tTreg) and peripheral (pTreg) Treg cells, respectively. While tTreg cells suppress autoimmunity, pTreg cells enforce tolerance to food and commensal microbiota. However, the role of Foxp3 in pTreg cells and the mechanisms supporting their differentiation remain poorly understood. Here, we used genetic tracing to identify microbiota-induced pTreg cells and found that many of their distinguishing features were Foxp3 independent. Lineage-committed, microbiota-dependent pTreg-like cells persisted in the colon in the absence of Foxp3. While Foxp3 was critical for the suppression of a Th17 cell program, colitis, and mastocytosis, pTreg cells suppressed colonic effector Tcell expansion in a Foxp3-independent manner. Thus, Foxp3 and the tolerogenic signals that precede and promote its expression independently confer distinct facets of pTreg functionality.

Paratympanic sinuses in juvenile Alligator.

Crocodylia has an extensive epithelial pneumatic space in the middle ear, paratympanic sinus system. Although fossil and extant crocodylian paratympanic sinus systems have been studied recently using the computed tomography (CT) and three-dimensional (3D) reconstruction data, due to the soft tissue nature of the pneumatic system and presence of its surrounding soft tissue structures, some boundaries, and definitions of each extension remain ambiguous. We describe the comprehensive paratympanic sinus system in posthatched alligator using soft tissue enhanced CT data with 3D reconstructions. The data are compared to the available data to discuss the ontogenetic pattern in alligator. We introduce further divided entities of the pneumatic system based on their associated bony and soft tissue structures and epithelial membrane and clarify the pneumatic terminologies. We then re-visit the potential homology of the paratympanic sinus in Archosauria. Epithelial boundaries of the ventral portion of the pneumatic system from the histological data suggest that the dual origin of the basioccipital diverticulum derived from the tympanic sinus and basicranial diverticulum medially. The presence of the epithelial boundary and pneumatic changes in ontogeny suggests that the middle ear may function differently in developmental stages. Lastly, a morphogenetic tree is constructed to help future work of comparative developmental studies of the paratympanic sinus system between crocodiles and birds.

Elp1‐Mediated Mechanisms Underlying Trigeminal Ganglion Development

The trigeminal nerve is the largest of the cranial nerves and relays sensations of pain, touch, and temperature from the face and head back to the brain. Cell bodies for this nerve are positioned in the trigeminal ganglion, which arises from the coalescence of neurons and supporting glia derived from two important embryonic cell populations, neural crest cells and placode cells. While the dual cellular origin of the trigeminal ganglion has been known for over 60 years, the molecular mechanisms controlling trigeminal ganglion development remain obscure. Our prior work has shown that the chick embryonic trigeminal ganglion initially forms from cadherin‐based interactions between neural crest cells and placode cells. In an effort to elucidate pathways regulating cadherin‐mediated trigeminal ganglion assembly, we identified Elongator complex protein 1 (Elp1) as a new regulator of trigeminal ganglion neuron development. Mutations in ELP1cause Familial Dysautonomia, an ultimately fatal disease characterized, in part, by the presence of small trigeminal nerves and a reduced capacity to sense facial pain and temperature. In a mouse model of Familial Dysautonomia, embryos possess trigeminal ganglion innervation deficits and decreased expression of cadherins in trunk neural crest‐derived dorsal root ganglia. While Elp1 is vital for neurogenesis and has been implicated in protein trafficking, cell adhesion, and migration, the role of Elp1 in the trigeminal ganglion is unexplored. We hypothesize that Elp1 regulates trigeminal ganglion development by controlling cadherin levels important for continued interactions between neural crest cell and placode cell derivatives. To address this, we have first generated a spatio‐temporal expression profile of Elp1 in the chick trigeminal ganglion using section immunohistochemistry. Our preliminary data indicate that Elp1 is expressed in migratory neural crest cells, trigeminal placode cells, and trigeminal placode cell‐derived neurons. Additionally, immunocytochemistry of chick trigeminal ganglion explant cultures revealed colocalization of Elp1 and Rab proteins associated with vesicle trafficking. Future experiments will include loss of function assays to investigate the relationship between Elp1 and cadherin trafficking in the trigeminal ganglion. Our results have potential high significance for providing new insights into the function of Elp1 in trigeminal ganglion development and the etiology of diseases like Familial Dysautonomia and others arising from defects in neural crest cells and/or placode cells.

Somatic mosaicism reveals clonal distributions of neocortical development.

The structure of the human neocortex underlies species-specific traits and reflects intricate developmental programs. Here we sought to reconstruct processes that occur during early development by sampling adult human tissues. We analysed neocortical clones in a post-mortem human brain through a comprehensive assessment of brain somatic mosaicism, acting as neutral lineage recorders1,2. We combined the sampling of 25 distinct anatomic locations with deep whole-genome sequencing in a neurotypical deceased individual and confirmed results with 5 samples collected from each of three additional donors. We identified 259 bona fide mosaic variants from the index case, then deconvolved distinct geographical, cell-type and clade organizations across the brain and other organs. We found that clones derived after the accumulation of 90-200 progenitors in the cerebral cortex tended to respect the midline axis, well before the anterior-posterior or ventral-dorsal axes, representing a secondary hierarchy following the overall patterning of forebrain and hindbrain domains. Clones across neocortically derived cells were consistent with a dual origin from both dorsal and ventral cellular populations, similar to rodents, whereas the microglia lineage appeared distinct from other resident brain cells. Our data provide a comprehensive analysis of brain somatic mosaicism across the neocortex and demonstrate cellular origins and progenitor distribution patterns within the human brain.

Dual Origin of Right Vertebral Artery in a Patient with Tetralogy of Fallot.

Dual Origin of Right Vertebral Artery in a Patient with Tetralogy of Fallot.

Intermediate Cells of Dual Embryonic Origin Follow a Basal to Apical Gradient of Ingression Into the Lateral Wall of the Cochlea.

Intermediate cells of the stria vascularis are neural crest derived melanocytes. They are essential for the establishment of the endocochlear potential in the inner ear, which allows mechanosensory hair cells to transduce sound into nerve impulses. Despite their importance for normal hearing, how these cells develop and migrate to their position in the lateral wall of the cochlea has not been studied. We find that as early as E10.5 some Schwann cell precursors in the VIIIth ganglion begin to express melanocyte specific markers while neural crest derived melanoblasts migrate into the otic vesicle. Intermediate cells of both melanoblast and Schwann cell precursor origin ingress into the lateral wall of the cochlea starting at around E15.5 following a basal to apical gradient during embryonic development, and continue to proliferate postnatally.

When did biopolitics begin? Actuality and potentiality in historical events

The article addresses the ongoing debate about the origins of biopolitics. While Foucault’s analysis of biopolitics approached it as a modern rationality of government, Agamben’s Homo Sacer series presented biopolitics as having a longer provenance, dating back to the antiquity. These polar positions are not mutually exclusive but coexist in these and other theories of biopolitics, which approach its object as both modern and ancient, having its chronological origin in the eighteenth to nineteenth centuries yet also possessing a prehistory of precursors. The article interprets this dual origin in terms of Paolo Virno’s theory of historical temporality, which distinguishes between the chronological past of historical events and their potential past, which accompanies and is negated in them. Coexisting with its own unrealized potential, every historical event remains incomplete and extends itself both backwards and forwards, positing its precursors and prefiguring its future outcomes. While modern in the chronological sense, biopolitics is retrospectively inscribed in a longer historical lineage, its antecedents easily identifiable in the history of political thought. Finally, we apply this approach to Virno’s own account of the history of biopolitics, questioning his identification of past potential with labour-power.

Assembly-dependent translation of subunits 6 (Atp6) and 9 (Atp9) of ATP synthase in yeast mitochondria.

The yeast mitochondrial ATP synthase is an assembly of 28 subunits of 17 types of which 3 (subunits 6, 8, and 9) are encoded by mitochondrial genes, while the 14 others have a nuclear genetic origin. Within the membrane domain (FO) of this enzyme, the subunit 6 and a ring of 10 identical subunits 9 transport protons across the mitochondrial inner membrane coupled to ATP synthesis in the extra-membrane structure (F1) of ATP synthase. As a result of their dual genetic origin, the ATP synthase subunits are synthesized in the cytosol and inside the mitochondrion. How they are produced in the proper stoichiometry from two different cellular compartments is still poorly understood. The experiments herein reported show that the rate of translation of the subunits 9 and 6 is enhanced in strains with mutations leading to specific defects in the assembly of these proteins. These translation modifications involve assembly intermediates interacting with subunits 6 and 9 within the final enzyme and cis-regulatory sequences that control gene expression in the organelle. In addition to enabling a balanced output of the ATP synthase subunits, these assembly-dependent feedback loops are presumably important to limit the accumulation of harmful assembly intermediates that have the potential to dissipate the mitochondrial membrane electrical potential and the main source of chemical energy of the cell.

Dual Origin of Left Vertebral Artery- A Case Report of an Uncommon Vascular Variant

Vertebral artery duplication is relatively an uncommon vascular variant. It is a developmental anomaly with a dual origin and has different levels of fusion in the neck. It is usually an incidental finding found during workup of other clinical conditions. Due to its anatomical similarity with arterial dissection it is often misinterpreted on vascular imaging so a thorough understanding of this vascular variant is necessary to avoid diagnostic and therapeutic complications during endovascular interventions. A 43-year-old male presented with complaints of pain and discolouration of fingers of left hand since 2 days. Computed Tomography (CT) angiography of upper limb was done which revealed short segment near complete to complete occlusion/thrombosis of proximal left subclavian artery which was seen 8 mm from its origin with distal reformation by the collaterals. There was an evidence of hypoplastic V1 segment of native left vertebral artery, a small artery was seen arising from the aortic arch in the middle of common carotid and left subclavian artery origins, which was found to be duplicated vertebral artery with dual origin from both the subclavian artery and aorta with fusion of both the limbs at C4-C5 levels.

The Milky Way Revealed by Variable Stars. I. Sample Selection of RR Lyrae Stars and Evidence for Merger History

Abstract In order to study the Milky Way, RR Lyrae (RRL) variable stars identified by Gaia, ASAS-SN, and ZTF sky survey projects have been analyzed as tracers in this work. Photometric and spectroscopic information of 3417 RRLs including proper motions, radial velocity, and metallcity are obtained from observational data of Gaia, LAMOST, GALAH, APOGEE, and RAVE. Precise distances of RRLs with typical uncertainties less than 3% are derived by using a recent comprehensive period–luminosity–metallicity relation. Our results from kinematical and chemical analysis provide important clues for the assembly history of the Milky Way, especially for the Gaia–Sausage ancient merger. The kinematical and chemical trends found in this work are consistent with those of recent simulations that indicated that the Gaia–Sausage merger had a dual origin in the Galactic thick disk and halo. As recent similar works have found, the halo RRL sample in this work contains a subset of radially biased orbits besides a more isotropic component. This higher orbital anisotropy component amounts to β ≃ 0.8, and it contributes between 42% and 83% of the halo RRLs at 4 < R( kpc) < 20.

Assessing contamination sources and environmental hazards for potentially toxic elements and organic compounds in the soils of a heavily anthropized area: the case study of the Acerra plain (Southern Italy)

<abstract> <p>Epidemiological and environmental studies demonstrated that the rate of cancer mortality in the Acerra area, better known as "Triangle of Death", and, more in general, in the Neapolitan metropolitan territory are higher than the regional average values. In the "Triangle of Death" the higher rate of mortality has been mostly related to the presence of toxic wastes illegally buried in agricultural areas which have been contaminating soils and groundwater for decades. Thus, collecting a total of 154 samples over an area of about 100 km<sup>2</sup>, a detailed study was carried out to assess the geochemical-environmental conditions of soils aiming at defining the environmental hazard proceeding from 15 potentially toxic elements (PTEs), 9 polycyclic aromatic hydrocarbons (PAHs) and 14 organochlorine pesticides (OCPs) related with soil contamination. The study was also targeted at discriminating the contamination sources of these pollutants. Results showed that 9 PTEs, 5 PAHs and 6 OCPs are featured by concentrations higher than the guideline values established by the Italian Environmental laws, especially in the proximities of inhabited centers and industrial areas. The contamination source analysis revealed that, as regards the concentrations of chemical elements, they have a dual origin due to both the natural composition of the soils (Co-Fe-V-Tl-Be) and the pressure exerted on the environment by anthropic activities such as vehicular traffic (Pb-Zn-Sb-Sn) and agricultural practices (Cu-P). As far as organic compounds are concerned, the source of hydrocarbons can be mainly attributed to the combustion of biomass (i.e., grass, wood and coal), while for pesticides, although the use of some of them has been prohibited in Italy since the 1980s, it has been found that they are still widely used by local farmers.</p> </abstract>

A rare unclassified coronary anomaly: Right coronary artery with dual ostia origin from the right aortic sinus of Valsalva

The dual ostia of coronary artery is extremely rare entity. We present a case of old woman with right coronary artery with dual ostia origin from the right aortic sinus of Valsalva. A 52-year-old woman presented with discontinuous chest tightness and palpitation. she was referred to coronary computed tomography angiography (CCTA). The CCTA suggested an anomalous right coronary artery (RCA) origin from the right sinus of Valsalva (RSV) with dual ostia. The dual ostia of coronary anomaly is extremely rare entity. Though catheter angiography may be performed for preoperative identification of coronary anomalies, it is limited in the description of the relationship of the coronary arteries to the cardiac structures and great vessels. CCTA can help in noninvasive characterization of coronary anomalies with respect to their origin, course, and spatial relations. Interventional cardiologists and cardiac surgeons should be aware of the new coronary anomaly for appropriate procedural planning and intra-procedural management. The important imaging valueof CCTA can help in noninvasive characterization of coronary anomalies with respect to their origin, course, and spatial relations.

IRC3 Regulates Mitochondrial Translation in Response to Metabolic Cues in Saccharomyces cerevisiae.

Mitochondrial oxidative phosphorylation (OXPHOS) enzymes have a dual genetic origin. Mechanisms regulating the expression of nucleus-encoded OXPHOS subunits in response to metabolic cues (glucose versus glycerol) are well understood, while the regulation of mitochondrially encoded OXPHOS subunits is poorly defined. Here, we show that IRC3, a DEAD/H box helicase gene, previously implicated in mitochondrial DNA maintenance, is central to integrating metabolic cues with mitochondrial translation. Irc3 associates with mitochondrial small ribosomal subunits in cells consistent with its role in regulating translation elongation based on the Arg8m reporter system. IRC3-deleted cells retained mitochondrial DNA despite a growth defect on glycerol plates. Glucose-grown Δirc3ρ+ and irc3 temperature-sensitive cells at 37°C have reduced translation rates from the majority of mRNAs. In contrast, when galactose was the carbon source, a reduction in mitochondrial translation was observed predominantly from Cox1 mRNA in Δirc3ρ+ cells but no defect was observed in irc3 temperature-sensitive cells, at 37°C. In support of a model whereby IRC3 responds to metabolic cues to regulate mitochondrial translation, Δirc3 suppressor strains isolated for restoration of growth on glycerol medium restore mitochondrial protein synthesis differentially in the presence of glucose versus glycerol.

The Cortical Motor System in the Domestic Pig: Origin and Termination of the Corticospinal Tract and Cortico-Brainstem Projections.

The anatomy of the cortical motor system and its relationship to motor repertoire in artiodactyls is for the most part unknown. We studied the origin and termination of the corticospinal tract (CST) and cortico-brainstem projections in domestic pigs. Pyramidal neurons were retrogradely labeled by injecting aminostilbamidine in the spinal segment C1. After identifying the dual origin of the porcine CST in the primary motor cortex (M1) and premotor cortex (PM), the axons descending from those regions to the spinal cord and brainstem were anterogradely labeled by unilateral injections of dextran alexa-594 in M1 and dextran alexa-488 in PM. Numerous corticospinal projections from M1 and PM were detected up to T6 spinal segment and showed a similar pattern of decussation and distribution in the white matter funiculi and the gray matter laminae. They terminated mostly on dendrites of the lateral intermediate laminae and the internal basilar nucleus, and some innervated the ventromedial laminae, but were essentially absent in lateral laminae IX. Corticofugal axons terminated predominantly ipsilaterally in the midbrain and bilaterally in the medulla oblongata. Most corticorubral projections arose from M1, whereas the mesencephalic reticular formation, superior colliculus, lateral reticular nucleus, gigantocellular reticular nucleus, and raphe received abundant axonal contacts from both M1 and PM. Our data suggest that the porcine cortical motor system has some common features with that of primates and humans and may control posture and movement through parallel motor descending pathways. However, less cortical regions project to the spinal cord in pigs, and the CST neither seems to reach the lumbar enlargement nor to have a significant direct innervation of cervical, foreleg motoneurons.

Sox6 expression distinguishes dorsally and ventrally biased dopamine neurons in the substantia nigra with distinctive properties and embryonic origins.

SUMMARYDopamine (DA) neurons in the ventral tier of the substantia nigra pars compacta (SNc) degenerate prominently in Parkinson’s disease, while those in the dorsal tier are relatively spared. Defining the molecular, functional, and developmental characteristics of each SNc tier is crucial to understand their distinct susceptibility. We demonstrate that Sox6 expression distinguishes ventrally and dorsally biased DA neuron populations in the SNc. The Sox6+ population in the ventral SNc includes an Aldh1a1+ subset and is enriched in gene pathways that underpin vulnerability. Sox6+ neurons project to the dorsal striatum and show activity correlated with acceleration. Sox6− neurons project to the medial, ventral, and caudal striatum and respond to rewards. Moreover, we show that this adult division is encoded early in development. Overall, our work demonstrates a dual origin of the SNc that results in DA neuron cohorts with distinct molecular profiles, projections, and functions.

Prenatal and Postnatal Development and also Morphological and Morphometric Indicators of Thymus in Newborns

The thymus is a lymphoepithelial organ located in the mediastinum and reaches its maximum development in youth. While other lymphoid organs develop exclusively from the mesenchyme (mesoderm), the thymus is of dual embryonic origin. Its lymphocytes develop in the bone marrow from cells of mesenchymal origin; they invade the epithelial bud, which has developed from the endoderm of the third and fourth pharyngeal pockets. The thymus is covered with a connective tissue capsule, which is introduced into the parenchyma and divides it into incomplete lobules, so the cortex and medulla of the adjacent lobules are connected to each other.