Early Branching Research Articles

Neuroblastoma plasticity during metastatic progression stems from the dynamics of an early sympathetic transcriptomic trajectory.

Despite their indisputable importance in neuroblastoma (NB) pathology, knowledge of the bases of NB plasticity and heterogeneity remains incomplete. They may be rooted in developmental trajectories of their lineage of origin, the sympatho-adrenal neural crest. We find that implanting human NB cells in the neural crest of the avian embryo allows recapitulating the metastatic sequence until bone marrow involvement. Using deep single cell RNA sequencing, we characterize transcriptome states of NB cells and their dynamics over time and space, and compare them to those of fetal sympatho-adrenal tissues and patient tumors and bone marrow samples. Here we report remarkable transcriptomic proximities restricted to an early sympathetic neuroblast branch that co-exist with phenotypical adaptations over disease progression and recapitulate intratumor and interpatient heterogeneity. Combining avian and patient datasets, we identify a list of genes upregulated during bone marrow involvement and associated with growth dependency, validating the relevance of our multimodal approach.

Phylogeny, Diversification, and Biogeography of Garra (Cypriniformes: Cyprinidae) Reveals Multiple Cross‐Drainage Dispersals in Southeast Asia

ABSTRACTGarra, a kind of small‐ to medium‐sized fish, is widely distributed from southern Eurasia to central Africa. As one of the most diverse genera of Cyprinidae, investigating the phylogeny and biogeography of Garra remains challenging. In this study, we combined sequences of Garra samples collected from Myanmar with sequences downloaded from GenBank to investigate the phylogeny, diversification, and biogeography of Garra on a global scale, with an emphasis on Southeast Asia. Species delimitation results indicated that there are at least 22 potential species, including eight undescribed species in Myanmar, suggesting that the diversity of Garra in this region have been largely underestimated. Diversification analysis suggested a relatively high diversification rate in the early branches of Garra. Ancestral distribution reconstruction results revealed that Garra originated from the Irrawaddy River basin in the late Eocene, approximately 34 million years ago, with subsequent dispersals across different drainages influenced by the uplift of the Qinghai‐Tibet Plateau. Our study provided a new insight into the evolutionary history of Garra and the basis for further research on this genus.

Lateral cell polarization drives organization of epithelia in sea anemone embryos and embryonic cell aggregates

One of the first organizing processes during animal development is the assembly of embryonic cells into epithelia. Common features unite epithelialization across select bilaterians, however, we know less about the molecular and cellular mechanisms that drive epithelial emergence in early branching nonbilaterians. In sea anemones, epithelia emerge both during embryonic development and after cell aggregation of dissociated tissues. Although adhesion is required to keep cells together, it is not clear whether cell polarization plays a role as epithelia emerge from disordered aggregates. Here, we use the embryos of the sea anemone Nematostella vectensis to investigate the evolutionary origins of epithelial development. We demonstrate that lateral cell polarization is essential for epithelial organization in both embryos and aggregates. With disrupted lateral polarization, cell contact in the aggregate is not sufficient to trigger epithelialization and further tissue development. Specifically, knockdown of the conserved lateral polarity and tumor suppressor protein Lethal giant larvae (Lgl) disrupts epithelia in developing embryos and impairs the capacity of dissociated cells to epithelialize from aggregates. In contrast to other systems, cells in Nematostella lgl knockdown embryos do not undergo excessive proliferation. Cells with reduced Lgl levels lose their columnar shape and proper positioning of their mitotic spindles and basal bodies. Due to misoriented divisions and aberrant shapes, cells arrange nonuniformly without forming a monolayer. Together our data show that, in Nematostella, Lgl drives epithelialization in embryos and cell aggregates through its effect on cell shape and organelle localization.

The osteohistology of Orthosuchus stormbergi using synchrotron radiation microcomputed tomography.

Orthosuchus stormbergi was a small-bodied crocodyliform, representative of a diverse assemblage of Early Jurassic, early branching crocodylomorph taxa from the upper Elliot Formation of South Africa. The life history of these early branching taxa remains poorly understood, with only sparse investigations into their osteohistology, yet species like Orthosuchus have potential to inform about the macroevolution of growth strategies on the stem leading to crown crocodilians. In order to elucidate the growth patterns of Orthosuchus, we used propagation phase contrast X-ray synchrotron micro-computed tomography to virtually image the osteohistology of the postcrania of two specimens, including multiple elements from the type (SAM-PK-K409), and the femur of a referred specimen (BP/1/4242). In total, we scanned nine mid-diaphyseal sections of the humerus, radius, ulna, radiale, femur, tibia, fibula, and a rib. We then compared our results to osteohistological sections of crocodylomorph taxa from the published literature. Our results show that the most predominant bone tissue type in Orthosuchus is lamellar, with a few patches of woven and parallel-fibred bone. The type specimen contains four to five lines of arrested growth and the hindlimb elements present outer circumferential lamellae, whereas the referred specimen contains six to seven. Both specimens grew at similar rates, reaching adult skeletal body size at year four or five. The sectioned bones, most notably the radius and ulna, are comparatively thick walled and compact. Our virtual osteohistological sections are one of the first for an early branching crocodyliform, and the broad sample of skeletal elements makes Orthosuchus a key anchor point for understanding the plesiomorphic life history traits of the clade.

Repeated shifts out of tropical climates preceded by whole genome duplication.

While flowering plants have diversified in virtually every terrestrial clime, climate constrains the distribution of individual lineages. Overcoming climatic constraints may be associated with diverse evolutionary phenomena including whole genome duplication (WGD), gene-tree conflict, and life-history changes. Climatic shifts may also have facilitated increases in flowering plant diversification rates. We investigate climatic shifts in the flowering plant order Ericales, which consists of c. 14 000 species with diverse climatic tolerances. We estimate phylogenetic trees from transcriptomic data, 64 chloroplast loci, and Angiosperms353 nuclear loci that, respectively, incorporate 147, 4508, and 2870 Ericales species. We use these phylogenetic trees to analyse how climatic shifts are associated with WGD, gene-tree conflict, life-history, and diversification rates. Early branches in the phylogenetic trees are extremely short, and have high levels of gene-tree conflict and at least one WGD. On lineages descended from these early branches, there is a significant association between climatic shifts (primarily out of tropical climates), further WGDs, and life-history. Extremely short early branches, and their associated gene-tree conflict and WGDs, appear to underpin the explosive origin of numerous species rich Ericales clades. The evolution of diverse climatic tolerances in these species rich clades is tightly associated with WGD and life-history.

An annotated checklist of Syzygium subgenus Sequestratum (Myrtaceae)

We present an annotated checklist of the 29 species comprising Syzygium subg. Sequestratum. Species in the subgenus were identified through a comprehensive review of herbarium specimens and relevant literature, including both historic taxonomic and regional revisions of Syzygium, and recent molecular phylogenetic analyses. No single character is diagnostic of subg. Sequestratum; instead, a combination of commonly occurring characters is used, including glaucescence in the hypanthium, funnel-shaped flowers <10 mm long and coriaceous leaves with dark drying petioles in contrast to a paler lamina. Species are distributed across East Asia, Malesia and Eastern Australia, with an apparent preference for nutrient-poor habitats. This checklist provides a foundation for future taxonomic revision of this clade, from an early branching node in the tree of life of the world’s largest tropical tree genus.

Early evolutionary branching across spatial domains predisposes to clonal replacement under chemotherapy in neuroblastoma

Neuroblastoma (NB) is one of the most lethal childhood cancers due to its propensity to become treatment resistant. By spatial mapping of subclone geographies before and after chemotherapy across 89 tumor regions from 12 NBs, we find that densely packed territories of closely related subclones present at diagnosis are replaced under effective treatment by islands of distantly related survivor subclones, originating from a different most recent ancestor compared to lineages dominating before treatment. Conversely, in tumors that progressed under treatment, ancestors of subclones dominating later in disease are present already at diagnosis. Chemotherapy treated xenografts and cell culture models replicate these two contrasting scenarios and show branching evolution to be a constant feature of proliferating NB cells. Phylogenies based on whole genome sequencing of 505 individual NB cells indicate that a rich repertoire of parallel subclones emerges already with the first oncogenic mutations and lays the foundation for clonal replacement under treatment.

Proton ingestion in asymptotic giant branch stars as a possible explanation for J-type stars and AB2 grains

J-type stars are a subclass of carbon stars that are generally Li-rich, not enriched in s-elements, and have low 12C/13C ratios. They were suggested to be the manufacturers of the pre-solar grains of type AB2 (having low 12C/13C and supersolar 14N/15N). In this Letter, we investigate the possibility that J-type stars are early asymptotic giant branch (AGB) stars that experienced a proton ingestion event (PIE). We used the stellar evolution code STAREVOL to compute AGB stellar models with initial masses of 1, 2, and 3 and metallicities Fe/H $= -0.5$ and 0.0. We included overshooting above the thermal pulse and used a network of 1160 nuclei coupled to the transport equations. The outputs of these models were compared to observations of J-type stars and AB2 grains. In solar-metallicity AGB stars, PIEs can be triggered if a sufficiently high overshoot is considered. These events lead to low 12C/13C ratios, high Li abundances, and no enrichment in s-elements. We find that the $2-3$ AGB models experiencing a PIE can account for most of the observational features of J-type stars and AB2 grains. The remaining tensions between models and observations are (1) the low 14N/15N ratio of some AB2 grains and of 2 out of 13 J-type stars, (2) the high 26Al/27Al of some AB2 grains, and (3) the J-type stars with A(Li) $<2$. Extra mixing mechanisms can alleviate some of these tensions, such as thermohaline or rotation. This work highlights a possible match between AGB stellar models that undergo a PIE and J-type stars and AB2 grains. To account for other types of carbon stars, such as N-type stars, PIEs should only develop in a fraction of solar-metallicity AGB stars. Additional work is needed to assess how the occurrence of PIEs depends on mixing parameters and initial conditions, and therefore to further confirm or exclude the proposed scenario.

Use of Branched EVAR in Treatment of Juxtarenal Aortic Aneurysm and Essential Accessory Renal Artery: Another Tool on the Shelf? A Case Report.

We present the case of a 58-year-old male patient referred to our department from a smaller facility for further evaluation and treatment strategy regarding the choice between open or endovascular surgery. The patient was diagnosed with a 6cm asymptomatic juxtarenal aortic aneurysm and a 5mm diameter accessory renal artery (ARA) supplying the lower half of left kidney. Further diagnostic assessments indicated that the left ARA was perfusing over 40% of the left kidney. Given the patient's significant pre-existing medical conditions and elevated perioperative risk, the decision was made to proceed with minimally invasive endovascular surgery using a custom-made 5-branches stent graft (BEVAR). In the early postoperative period, the patient reported left flank pain. A subsequent CT scan identified a partial infarction in the left kidney due to the occlusion of an early small branch from the upper left renal artery. However, laboratory results showed no significant change in renal function compared to preoperative values. The patient was discharged 6 days post-surgery, with no additional complications observed during the early postoperative period. This case report demonstrates that BEVAR is acceptable technique with satisfactory early postoperative outcomes for treating juxtarenal aortic aneurysms with an accessory renal artery in patients who are high-risk candidates for open repair and anatomically unsuitable for FEVAR or Ch-EVAR procedures.

Discovery of a Metal-poor Red Giant Star with the Highest Ultralithium Enhancement

We present the discovery of 2MASS J05241392−0336543 (hereafter J0524−0336), a very metal-poor ([Fe/H] = −2.43 ± 0.16), highly r-process-enhanced ([Eu/Fe] = +1.34 ± 0.10) Milky Way halo field red giant star, with an ultrahigh Li abundance of A(Li, 3D, NLTE) = 6.15 ± 0.25 and [Li/Fe] = +7.64 ± 0.25, respectively. This makes J0524−0336 the most lithium-enhanced giant star discovered to date. We present a detailed analysis of the star’s atmospheric stellar parameters and chemical abundance determinations. Additionally, we detect indications of infrared excess, as well as observe variable emission in the wings of the Hα absorption line across multiple epochs, indicative of a potential enhanced mass-loss event with possible outflows. Our analysis reveals that J0524−0336 lies either between the bump and the tip of the red giant branch (RGB), or on the early asymptotic giant branch (e-AGB). We investigate the possible sources of lithium enrichment in J0524−0336, including both internal and external sources. Based on current models and on the observational evidence we have collected, our study shows that J0524−0336 may be undergoing the so-called lithium flash that is expected to occur in low-mass stars when they reach the RGB bump and/or the e-AGB.

A Brown Dwarf Orbiting around the Planetary-nebula Central Binary KV Vel

KV Vel is a noneclipsing short-period (P = 0.3571 days) close binary containing a very hot subdwarf primary (77,000 K) and a cool low-mass secondary star (3400 K) that is located at the center of the planetary nebula DS 1. The changes in the orbital period of the close binary were analyzed based on 262 new times of light maximum together with those compiled from the literature. It is discovered that the O − C curve shows a small-amplitude (0.ͩ0034) cyclic period variation with a period of 29.55 yr. The explanation by the solar-type magnetic activity cycles of the cool component is ruled out because the required energies are much larger than the total radiant energy of this component in a whole cycle. Therefore, the cyclic variation was plausibly explained as the light-travel time effect via the presence of a tertiary component, which is supported by the periodic changes of the O − C curve and the rather symmetric and stable light curves obtained by the Transiting Exoplanet Survey Satellite. The mass of the tertiary companion is determined to be M3sini′=0.060(±0.007) M ⊙. If the third body is coplanar with the central binary (i.e., i′=62.°5 ), the mass of the tertiary component is computed as M 3 ∼ 0.068 M ⊙, and thus it would be below the stable hydrogen-burning limit and is a brown dwarf. The orbital separation is shorter than 9.35 au. KV Vel together with its surrounding planetary nebula and the brown-dwarf companion may be formed through the common-envelope evolution after the primary filled its Roche lobe during the early asymptotic giant branch stage.

Leaf functional trait evolution and its putative climatic drivers in African Coffea species.

Leaf traits are known to be strong predictors of plant performance and can be expected to (co)vary along environmental gradients. We investigated the variation, integration, environmental relationships, and evolutionary history of leaf functional traits in the genus Coffea L., typically a rainforest understory shrub, across Africa. A better understanding of the adaptive processes involved in leaf trait evolution can inform the use and conservation of coffee genetic resources in a changing climate. We used phylogenetic comparative methods to investigate the evolution of six leaf traits measured from herbarium specimens of 58 African Coffea species. We added environmental data and data on maximum plant height for each species to test trait-environment correlations in various (sub)clades, and we compared continuous trait evolution models to identify variables driving trait diversification. A substantial leaf trait variation was detected across the genus Coffea in Africa, which was mostly interspecific. Of these traits, stomatal size and stomatal density exhibited a clear trade-off. We observed low densities of large stomata in early branching lineages and higher densities of smaller stomata in more recent taxa, which we hypothesise to be related to declining CO2 levels since the mid-Miocene. Brownian Motion evolution was rejected in favour of White Noise or Ornstein-Uhlenbeck models for all traits, implying these traits are adaptively significant rather than driven by pure drift. The evolution of leaf area was likely driven by precipitation, with smaller leaves in dryer climates across the genus. Generally, Coffea leaf traits appear to be evolutionarily labile and governed by stabilising selection, though evolutionary patterns and correlations differ depending on the traits and clades considered. Our study highlights the importance of a phylogenetic perspective when studying trait relationships across related taxa, as well as the consideration of various taxonomic ranges.

Preoperative visualization of the greater occipital nerve with magnetic resonance imaging in candidates for occipital nerve decompression for headaches

Occipital nerve decompression is effective in reducing headache symptoms in select patients with migraine and occipital neuralgia. Eligibility for surgery relies on subjective symptoms and responses to nerve blocks and Onabotulinum toxin A (Botox) injections. No validated objective method exists for detecting occipital headache pathologies. The purpose of the study is to explore the potential of high-resolution Magnetic Resolution Imaging (MRI) in identifying greater occipital nerve (GON) pathologies in chronic headache patients. The MRI protocol included three sequences targeting fat-suppressed fluid-sensitive T2-weighted signals. Visualization of the GON involved generating 2-D image slices with sequential rotation to track the nerve course. Twelve patients underwent pre-surgical MRI assessment. MRI identified four main pathologies that were validated against intra-operative examination: GON entanglement by the occipital artery, increased nerve thickness and hyperintensity suggesting inflammation compared to the non-symptomatic contralateral side, early GON branching with rejoining at a distal point, and a connection between the GON and the lesser occipital nerve. MRI possesses the ability to visualize the GON and identify suspected trigger points associated with headache symptoms. This case series highlights MRI's potential to provide objective evidence of nerve pathology. Further research is warranted to establish MRI as a gold standard for diagnosing extracranial contributors in headaches.

Prevalence of Anatomical Variant Renal arterial diameter, Early Prehilar Branching and Multiplicity on Contrast Enhanced Computed Tomography Scans

Prevalence of Anatomical Variant Renal arterial diameter, Early Prehilar Branching and Multiplicity on Contrast Enhanced Computed Tomography Scans

Predicting Occluded Middle Cerebral Artery Morphology for Endovascular Mechanical Thrombectomy: A Contralateral Shape Analysis Approach.

Introduction Predicting the shape of the occluded middle cerebral artery (MCA) from the contralateral MCA might help catheterization in endovascular mechanical thrombectomy (EMT). Materials and Methods We analyzed magnetic resonance (MR) angiography in 100 consecutive patients who had MR imaging for diseases other than acute ischemic stroke. To assess the symmetricity of MCA, the shape of M1, length of M1, number of M2, number of early branches (EBs), and distance from the top of the internal carotid artery to EB were investigated. Results The shape of M1 was upward in 42%, horizontal in 47%, and downward in 11%. The M1 shape was the same on both sides in 64%, which exceeded the probability assumed to be left-right independent. The number of M2 trunks and EBs matched left and right in 86 and 55% of patients, respectively; however, these agreement rates were not higher than those with independent left and right sides. No left-right correlation was found between the M1 length and the distance from the internal carotid artery to EB. Conclusion Based on our data, the symmetry of MCA was observed only in the shape of the M1 segment. This finding could be beneficial for EMT targeting MCA embolisms.

Regeneration in the absence of canonical neoblasts in an early branching flatworm.

The remarkable regenerative abilities of flatworms are closely linked to neoblasts - adult pluripotent stem cells that are the only division-competent cell type outside of the reproductive system. Although the presence of neoblast-like cells and whole-body regeneration in other animals has led to the idea that these features may represent the ancestral metazoan state, the evolutionary origin of both remains unclear. Here we show that the catenulid Stenostomum brevipharyngium, a member of the earliest-branching flatworm lineage, lacks conventional neoblasts despite being capable of whole-body regeneration and asexual reproduction. Using a combination of single-nuclei transcriptomics, in situ gene expression analysis, and functional experiments, we find that cell divisions are not restricted to a single cell type and are associated with multiple fully differentiated somatic tissues. Furthermore, the cohort of germline multipotency genes, which are considered canonical neoblast markers, are not expressed in dividing cells, but in the germline instead, and we experimentally show that they are neither necessary for proliferation nor regeneration. Overall, our results challenge the notion that canonical neoblasts are necessary for flatworm regeneration and open up the possibility that neoblast-like cells may have evolved convergently in different animals, independent of their regenerative capacity.

Floral morphology and development of Pteridophyllum racemosum Siebold & Zucc. (Papaveraceae)

ABSTRACT Papaveraceae are known for their often showy flowers and diverse morphologies. Pteridophyllum racemosum (Siebold & Zucc.) is the only member in the Pteridophylloideae within the Papaveraceae, and its phylogenetic position has long been controversial, and a comprehensive analysis of its floral morphology was lacking. Our study focuses on the floral morphogenesis of P. racemosum. Histological sections complemented with scanning electron microscopy allowed a detailed characterization of P. racemosum floral development including description of the vegetative morphology, showing (1) the fine structure of the unusual pinnate leaves; (2) the well-defined floral structure and disymmetry; (3) a series of landmarks in floral development stages, with emphasis on the development of the gynoecium. Interestingly, the P. racemosum floral architecture is similar to that of the proposed ancestral Papaveraceae flower supporting the phylogenetic placement of P. racemosum as an early branching lineage within the Papaveraceae. Our comprehensive overview adds to the colorful library of floral diversity in Papaveraceae, providing a solid base for comparative analyses.

The complete mitochondrial genome of Neuroctenus taiwanicus (Hemiptera: Aradidae)

Neuroctenus taiwanicus Kormilev, 1955 is a flat-bodied and enigmatic bug that was first discovered on the island of Taiwan, China. In this study, the whole mitochondrial genome of N. taiwanicus was sequenced and annotated for the first time, and its genomic data were uploaded to Genbank feedback number OR675057. The mitochondrial genome of N. taiwanicus is 15,340 bp in length, a typical circular DNA encoding 37 genes and a control region with 68.4% A + T content. The phylogeny reveals the taxonomic status of N. taiwanicus, which is most closely related to N. yunnanensis, and demonstrates the sister relationship among Neuroctenus, Mezira, and Brachyrhynchus. In addition, the results also confirm that Aradinae and Calisiinae are the earliest branching and more primitive in the family Aradidae, which is consistent with the analysis of the traditional classification.

Mining the GALAH Data. I. Study of Five Super Lithium-rich Metal-poor Giants

Abstract The presence of a large amount of Li in giants is still a mystery. Most of the super Li-rich (SLR) giants reported in recent studies are in the solar metallicity regime. Here, we study the five metal-poor SLRs from the Galactic Archeology with HERMES Data Release 3, with their [Fe/H] ranging from −1.35 to −2.38 with lithium abundance of A(Li) ≥ 3.4 dex. The asteroseismic analysis reveals that none are on the red giant branch. The average period spacing (ΔP ) values indicate giants are in the core He-burning phase. All of them are low-mass giants (M < 1.5 M ⊙). Their location in the Hertzsprung–Russell diagram suggests one of them is in the red clump (RC) phase, and interestingly, the other four are much brighter and coincide with the early asymptotic giant branch phase. The analysis of the abundance reveals that C, O, Na, Ba, and Eu are normal in giants of respective metallicities and evolutionary phases. Further, we did not find any strong evidence of the presence of dust in the form of infrared excess or binarity from the available radial velocity data. We discuss a few scenarios for the existence of SLRs at higher luminosity, including past merger events. Our findings will help in understanding the production and evolution of Li among giants, in particular, during the RC phase and the post-RC phase.

Simulation of range code tracking loop for multipath mitigation in NavIC receiver

Abstract The Operational Navigation with Indian Constellation (NavIC) comprises seven satellites in the orbit, including three in geostationary orbit (GEO) and four in geosynchronous orbit (GSO). NavIC provides both Standard Positioning Service and Restricted Service, using L5 (1176.45 MHz) and S1 (2492.028 MHz) frequencies, with coverage extending 1500 km around the mainland of India. In an urban canyon, multipath interference severely reduces the precision and reliability of NavIC positioning. Many current multipath mitigation techniques often exhibit high computational requirements or reliance on external assistance. In this paper, a ranging code tracking loop is proposed that can sustain either a late or early branch in contrast to the Narrow-Spacing (NS) correlation technique for mitigating multipath for NavIC receiver. The design of proposed code tracking loop is based on steepest descent algorithm. The findings demonstrate that, in terms of calculation time and code multipath mitigation, the suggested technique performs better than both Multipath Estimated Delay Locked Loop (MEDL) and NS correlation. The proposed method produces less than 0.016 chips for the tracking error Standard Deviation (STD). In addition, the recommended method takes 24 % less computation time.