Spatial Origin Research Articles

Abstract A006: Cancer origin tracing and timing in two high risk prostate cancers using multisample whole genome analysis: Potential clinical value

Abstract Prostate cancer (PrCa) genomic heterogeneity causes resistance to therapies such as androgen deprivation. Such heterogeneity can be deciphered in the context of evolutionary principles, but current clinical trials do not include evolution as an essential feature. Understanding the evolution of an individual PrCa through serial analysis in space and time may be more important than identifying actionable targets for therapy from single samples as in current practice. The most prominent recent example of this is our recent evolution-based discovery of subclone eradication in a metastatic PrCa, with subsequent identification of a novel method to compare eradicated and resistant subclones to better resolve actionable targets for therapy. Whether or not analysis of genomic data in an evolutionary context in primary prostate cancer can provide unique added value in the research and clinical domains remains an open question. We used novel processing techniques to obtain whole genome data together with 3D anatomic and histomorphologic analysis in two men (GP5 and GP12) with high risk PrCa undergoing radical prostatectomy. A total of 22 whole genome-sequenced sites (16 primary cancer foci and 6 lymph node metastatic) were analyzed using evolutionary reconstruction tools and spatio-evolutionary models. Probability models were used to trace spatial and chronological origins of the primary tumor and metastases, chart their genetic drivers, and distinguish metastatic and non-metastatic subclones. In patient GP5, CDK12 inactivation was among the first mutations, leading to a PrCa tandem duplicator phenotype and initiating the cancer around age 50, followed by rapid cancer evolution after age 57, and metastasis around age 59, five years prior to prostatectomy. In patient GP12, accelerated cancer progression was detected after age 54, and metastasis occurred around age 56, three years prior to prostatectomy. Multiple metastasis-originating events were identified in each patient and tracked anatomically. Metastasis from prostate to lymph nodes occurred strictly ipsilaterally in all 12 detected events. In this pilot, metastatic subclone content analysis appears to substantially enhance identification of key drivers. Evolutionary analysis’ potential impact on therapy selection appears positive in these pilot cases. Taken together with our recent discovery that solid tumor subclones can be eradicated, and that comparison of eradicated and resistant subclones could guide therapy, we believe the case for embarking on clinical trials testing evolutionary-analysis informed PrCa care is compelling. PrCa evolutionary analysis allows tracking of anatomic site of origin, timing of cancer origin and spread, and distinction of metastatic-capable from non-metastatic subclones. This enables better identification of actionable targets for therapy. If extended to larger cohorts, it appears likely that similar analyses could add substantial biological insight and clinically relevant value. Citation Format: Anssi Nurminen, Serafiina Jaatinen, Sinja Taavitsainen, Gunilla Högnäs, Tom Lesluyes, Naser Ansari-Pour, Teemu Tolonen, Kerstin Haase, Antti Koskenalho, Matti Kankainen, Juho Jasu, Hanna Rauhala, Jenni Kesäniemi, Tiia Nikupaavola, Paula Kujala, Irina Rinta-Kiikka, Jarno Riikonen, Antti Kaipia, Teemu Murtola, Teuvo L. Tammela, Tapio Visakorpi, Matti Nykter, David C. Wedge, Peter Van Loo, G. Steven Bova. Cancer origin tracing and timing in two high risk prostate cancers using multisample whole genome analysis: Potential clinical value [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Translating Cancer Evolution and Data Science: The Next Frontier; 2023 Dec 3-6; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(3 Suppl_2):Abstract nr A006.

Impaired oligodendrogenesis in the white matter of aged mice following diffuse traumatic brain injury.

Senescence is a negative prognostic factor for outcome and recovery following traumatic brain injury (TBI). TBI-induced white matter injury may be partially due to oligodendrocyte demise. We hypothesized that the regenerative capacity of oligodendrocyte precursor cells (OPCs) declines with age. To test this hypothesis, the regenerative capability of OPCs in young [(10 weeks ±2 (SD)] and aged [(62 weeks ±10 (SD)] mice was studied in mice subjected to central fluid percussion injury (cFPI), a TBI model causing widespread white matter injury. Proliferating OPCs were assessed by immunohistochemistry for the proliferating cell nuclear antigen (PCNA) marker and labeled by 5-ethynyl-2'-deoxyuridine (EdU) administered daily through intraperitoneal injections (50 mg/kg) from day 2 to day 6 after cFPI. Proliferating OPCs were quantified in the corpus callosum and external capsule on day 2 and 7 post-injury (dpi). The number of PCNA/Olig2-positive and EdU/Olig2-positive cells were increased at 2dpi (p < .01) and 7dpi (p < .01), respectively, in young mice subjected to cFPI, changes not observed in aged mice. Proliferating Olig2+/Nestin+ cells were less common (p < .05) in the white matter of brain-injured aged mice, without difference in proliferating Olig2+/PDGFRα+ cells, indicating a diminished proliferation of progenitors with different spatial origin. Following TBI, co-staining for EdU/CC1/Olig2 revealed a reduced number of newly generated mature oligodendrocytes in the white matter of aged mice when compared to the young, brain-injured mice (p < .05). We observed an age-related decline of oligodendrogenesis following experimental TBI that may contribute to the worse outcome of elderly patients following TBI.

Genomic Architecture Predicts Tree Topology, Population Structuring, and Demographic History in Amazonian Birds.

Geographic barriers are frequently invoked to explain genetic structuring across the landscape. However, inferences on the spatial and temporal origins of population variation have been largely limited to evolutionary neutral models, ignoring the potential role of natural selection and intrinsic genomic processes known as genomic architecture in producing heterogeneity in differentiation across the genome. To test how variation in genomic characteristics (e.g. recombination rate) impacts our ability to reconstruct general patterns of differentiation between species that cooccur across geographic barriers, we sequenced the whole genomes of multiple bird populations that are distributed across rivers in southeastern Amazonia. We found that phylogenetic relationships within species and demographic parameters varied across the genome in predictable ways. Genetic diversity was positively associated with recombination rate and negatively associated with species tree support. Gene flow was less pervasive in genomic regions of low recombination, making these windows more likely to retain patterns of population structuring that matched the species tree. We further found that approximately a third of the genome showed evidence of selective sweeps and linked selection, skewing genome-wide estimates of effective population sizes and gene flow between populations toward lower values. In sum, we showed that the effects of intrinsic genomic characteristics and selection can be disentangled from neutral processes to elucidate spatial patterns of population differentiation.

A Guinea Pig Model Suggests That Objective Assessment of Acoustic Hearing Preservation in Human Ears With Cochlear Implants Is Confounded by Shifts in the Spatial Origin of Acoustically Evoked Potential Measurements Along the Cochlear Length.

Our recent empirical findings have shown that the auditory nerve compound action potential (CAP) evoked by a low-level tone burst originates from a narrow cochlear region tuned to the tone burst frequency. At moderate to high sound levels, the origins shift to the most sensitive audiometric regions rather than the extended high-frequency regions of the cochlear base. This means that measurements evoked from extended high-frequency sound stimuli can shift toward the apex with increasing level. Here we translate this study to understand the spatial origin of acoustically evoked responses from ears that receive cochlear implants, an emerging area of research and clinical practice that is not completely understood. An essential step is to first understand the influence of the cochlear implant in otherwise naive ears. Our objective was to understand how function of the high-frequency cochlear base, which can be excited by the intense low-frequency sounds that are frequently used for objective intra- and postoperative monitoring, can be influenced by the presence of the cochlear implant. We acoustically evoked responses and made measurements with an electrode placed near the guinea pig round window. The cochlear implant was not utilized for either electrical stimulation or recording purposes. With the cochlear implant in situ, CAPs were acoustically evoked from 2 to 16 kHz tone bursts of various levels while utilizing the slow perfusion of a kainic acid solution from the cochlear apex to the cochlear aqueduct in the base, which sequentially reduced neural responses from finely spaced cochlear frequency regions. This cochlear perfusion technique reveals the spatial origin of evoked potential measurements and provides insight on what influence the presence of an implant has on acoustical hearing. Threshold measurements at 3 to 11 kHz were elevated by implantation. In an individual ear, thresholds were elevated and lowered as cochlear implant was respectively inserted and removed, indicative of "conductive hearing loss" induced by the implant. The maximum threshold elevation occurred at most sensitive region of the naive guinea pig ear (33.66 dB at 8 kHz), making 11 kHz the most sensitive region to acoustic sounds for guinea pig ears with cochlear implants. Conversely, the acute implantation did not affect the low-frequency, 500 Hz thresholds and suprathreshold function, as shown by the auditory nerve overlapped waveform. As the sound pressure level of the tone bursts increased, mean data show that the spatial origin of CAPs along the cochlear length shifted toward the most sensitive cochlear region of implanted ears, not the extended high-frequency cochlear regions. However, data from individual ears showed that after implantation, measurements from moderate to high sound pressure levels originate in places that are unique to each ear. Alterations to function of the cochlear base from the in situ cochlear implant may influence objective measurements of implanted ears that are frequently made with intense low-frequency sound stimuli. Our results from guinea pigs advance the interpretation of measurements used to understand how and when residual acoustic hearing is lost in human ears receiving a cochlear implant.

Assessment of heavy metals at mangrove ecosystem, applying multiple approaches using in-situ and remote sensing techniques, Red Sea, Egypt.

Mangrove areas are considered the most retention zone for heavy metal pollution as it work as an edge that aggregates land and sea sediments. This study aims to examine if the heavy metals' existence in the mangrove sediment is related to contamination or natural resources. In addition, it gives an interpretation of the origin of these metals along the Egyptian Red Sea coast. Twenty-two samples of mangrove sediments were collected and then, analyzed for metals (Mn, Ni, Cu, Fe, Cd, Ag, and Pb) using inductively coupled plasma mass spectroscopy (ICP-MS). Integration between the in-situ data, contamination indices, and remote sensing and geographical information science (GIS), and multivariate statistical analysis techniques (PCA) were analyzed to assess and clarify the spatial origin of heavy metals in sediment at a regional scale. The average concentration of heavy metals from mangrove sediments were shown to be substantially lower than the referenced value, ranging from moderate to significant except the levels of Ag were very high. The heavy metals concentrations were expected to be naturally origin rather than anthropogenic and that be confirmed by mapping of Red Sea alteration zones spots. These alteration zones are parallel to mangrove sites and rich by several mineralization types including heavy metals that are carried by flooding to the coastline. Remote sensing and GIS techniques successfully contributed to interpreting the pattern of the origin of heavy metals and discharging systems that control the heavy metals concentration along the Red Sea coast.

Material-agnostic characterization of spatially offset Raman spectroscopy in turbid media via Monte Carlo simulations.

Spatially offset Raman spectroscopy (SORS) is a transformative method for probing subsurface chemical compositions in turbid media. This systematic study of Monte Carlo simulations provides closed-form characterizations of key SORS parameters, such as the distribution of spatial origins of collected Raman photons and optimal SORS geometry to selectively interrogate a subsurface region of interest. These results are unified across an extensive range of material properties by multiplying spatial dimensions by the medium's effective attenuation coefficient, which can be calculated when the absorption and reduced scattering coefficients are known from the literature or experimentation. This method of spatial nondimensionalization is validated via goodness-of-fit analysis on the aggregate models and by training a subsurface sample localization model on a heterogeneous population of materials. The findings reported here advance the understanding of SORS phenomena while providing a quantitative and widely applicable foundation for designing and interpreting SORS experiments, facilitating its application in disciplines such as biomedical, materials science, and cultural heritage fields.

Craniological analysis of the muskrat (Ondatra zibethicus) from different river basins of Ukraine

The paper presents the results of a comprehensive craniological analysis of muskrats (Ondatra zibethicus Linnaeus, 1766) from five river basins of Ukraine: Dnipro (Lower Dnipro, Kherson Oblast), Snihurivka (irrigation canal, Mykolaiv Oblast), Danube (Lower Danube, Odesa Oblast), Dnister (Middle Dnister, Lviv and Ternopil oblasts), and Donets (Siversky Donets, Luhansk and Kharkiv oblasts). In total, 72 skulls were analysed using methods of traditional and geometric morphometrics. The craniometrical analysis included 14 measurements that describe general dimensions of the skull and its elements, whereas shape analysis was carried out separately for the dorsal and ventral surfaces of the skull and the buccal surface of the left mandible. The study revealed that muskrats from the Donets basin have the smallest skulls, whereas the other four samples greatly overlap. According to the results of multivariate analyses (PCA, CVA), the length and height of the mandible contribute the most into the differentiation of the samples. Geometric morphometrics showed that the most important distinguishing features include the shape of the nasal and parietal bones on the dorsal side, and of structures mainly related to the diastema and proximal part of the hard palatine on the ventral side. The most significant differences between the five samples, however, depend on the shape and relative orientation of the elements of the ascending ramus of the jaw—the coronoid, condylar, and angular processes, as well as the shape of bights between them and of the adjacent curvatures on the dorsal and ventral sides of the ascending ramus. The revealed features allow suggesting that the main contributing factors into the variation of geographically distinct populations include diet and feeding adaptations on the one hand, and possible spatial relationships and origin on the other. The Ukrainian sample also notably differs from muskrats from geographically distant regions by the mean values of several craniometrical characters, also indicating that animals in areas of secondary introduction have smaller cranial dimensions.

Laure Prouvost’s Deep See Blue Surrounding You

This paper aims to demonstrate how Laure Prouvost’s artistic practice requires an immersion of the viewer in intermedial installations composed of objects from the most disparate spatial and temporal origins. Since the early 2000s, the French artist has intentionally created surreal mise-en-scenes which, by blending video, painting, drawing, sculpture, and performance, can be understood as compositions or collages made of visual references taken from different contexts such as pop culture, the web, and private photo albums. Prouvost’s works are “unstable visual entities,” made of images that aggregate in heterogeneous configurations, generating eccentric atmospheres and cancelling every hierarchical order between the observer and the observed. Viewers are encouraged to fill the space by becoming objects among other objects. By using the Object-Oriented Ontology (OOO) as philosophical and methodological support, this paper will focus more closely on the analysis of Deep See Blue Surrounding You / Vois Ce Bleu Profond Te Fondre (2019), the project Prouvost produced for the French Pavilion at the 58th Venice Biennale. On this occasion, her work They Parlaient Idéale (2019) – a video documenting the Mediterranean Sea journey that brings her to the Venetian lagoon – was the cornerstone of a multifaceted environmental installation. Assuming a critical and analytical approach, this contribution then discusses the role Deep See Blue Surrounding You plays as a “hyper-enactment:” it is a mise-en-scene that consists of interrelationships between “things/images” that aggregate as objects, but it is also a composition in which the viewers are “viscously” asked to generate their personal, non-linear narration.

Descriptions and patterns in opportunistic marine debris collected near Palmer Station, Antarctica

Observations of marine debris in Antarctica have been increasing; however, impacts, distributions, sources, and transport pathways of debris remain poorly understood. Here, we describe the spatial distribution, types, and potential origins of marine debris in 2022/2023 near Palmer Station, Antarctica. We opportunistically collected 135 pieces of marine debris with the majority of items found along shorelines (90 %), some found in/near seabird nests/colonies (7 %) and few on inland rocky terrain (3 %). Plastic and abandoned, lost, or discarded fishing gear dominated observed debris. Results suggest that wind and the Antarctic Coastal Current may be a major pathway for debris. This study is the first assessment of marine debris in this region and suggests that oceanography, weather patterns, and shoreline geomorphology could play a role in determining where debris will accumulate. Continued tracking of debris and development of structured surveys is important for understanding the impacts of human activities in a biological hotspot.

Identifying the pathways of extreme rainfall in South Africa using storm trajectory analysis and unsupervised machine learning techniques

Abstract This study has utilised National Oceanic and Atmospheric Administration (NOAA) NCEP/NCAR Reanalysis 1 project meteorological data and the HYSPLIT model to extract the air parcel trajectories for selected historical extreme rainfall events in South Africa. The k-means unsupervised machine learning algorithm has been used to cluster the resulting trajectories, and from this, the spatial origin of moisture for each of the rainfall events has been determined. It has been demonstrated that rainfall events on the east coast with moisture originating from the Indian Ocean have distinctly larger average maximum daily rainfall magnitudes (279 mm) compared to those that occur on the west coast with Atlantic Ocean influences (149 mm) and those events occurring in the central plateau (150 mm) where moisture has been continentally recirculated. Further, this study has suggested new metrics by which the HYSPLIT trajectories may be assessed and demonstrated the applicability of trajectory clustering in a region not previously studied. This insight may in future facilitate improved early warning systems based on monitoring of atmospheric systems, and an understanding of rainfall magnitudes and origins can be used to improve the prediction of design floods for infrastructure design.

Spatial Variation, Ecological Risk, and Point Sources of Environmental Trace Metals in Lacustrine Ecosystems: An Assessment of Natural and Urban Inputs

ABSTRACT To gain insights into the spatial distribution, ecological risk and origins of heavy metals in surface sediments of lacustrine ecosystems in Cameroon, the content of 7 trace metals (Fe, Cr, Zn, Cu, Ni, Pb and Cd) in sediments from 60 sampling stations in 5 lacustrine environments of different formation contexts. The selected metals were investigated based on inductively coupled plasma mass spectrometry. The results revealed that the average concentrations of Cr, Cu and Cd were higher than the geochemical Threshold values. On the basis of the spatial variation, the studied metals vary quantitatively in the following order: Fe > Cr > Zn > Cu > Ni > Pb > Cd. The calculated enrichment factor (EF) and geo-accumulation index (Igeo) showed that, sediments from large cities and industrial sites had moderate enrichment (3 < EF ≤ 5) and were moderately to severely contaminated (2 < Igeo < 3) while those from low population and rural areas had minor enrichment (1 < EF ≤ 3) and were moderately contaminated (1 < Igeo < 2). With regards to cumulative pollution, the pollution load index (PLI) and the sediment pollution index (SPI) coupled with the potential ecological risk factor (Er) and the potential ecological risk index (RI), the sediments of the lakes are polluted (SPI and PLI > 1) to some extent but with a low ecological risk (Er < 40 and RI < 150). The results of Pearson correlation, principal component analysis (PCA), and cluster analysis (CA) identified three main sources: Ni would have a natural source; Pb from anthropogenic sources, and the other metals (Fe, Cr, Zn, Cu, and Cd) could have a mixed source (anthropogenic and natural). These findings serve as a scientific foundation for the advancement and use of these lake environments, which are the most attractive sites.

Range of chromatin accessibility configurations are permissive of GABAergic fate acquisition in developing mouse brain

In recent single-cell -omics studies, both the differential activity of transcription factors regulating cell fate determination and differential genome activation have been tested for utility as descriptors of cell types. Naturally, genome accessibility and gene expression are interlinked. To understand the variability in genomic feature activation in the GABAergic neurons of different spatial origins, we have mapped accessible chromatin regions and mRNA expression in single cells derived from the developing mouse central nervous system (CNS). We first defined a reference set of open chromatin regions for scATAC-seq read quantitation across samples, allowing comparison of chromatin accessibility between brain regions and cell types directly. Second, we integrated the scATAC-seq and scRNA-seq data to form a unified resource of transcriptome and chromatin accessibility landscape for the cell types in di- and telencephalon, midbrain and anterior hindbrain of E14.5 mouse embryo. Importantly, we implemented resolution optimization at the clustering, and automatized the cell typing step. We show high level of concordance between the cell clustering based on the chromatin accessibility and the transcriptome in analyzed neuronal lineages, indicating that both genome and transcriptome features can be used for cell type definition. Hierarchical clustering by the similarity in accessible chromatin reveals that the genomic feature activation correlates with neurotransmitter phenotype, selector gene expression, cell differentiation stage and neuromere origins.

Spatial transcriptomics and the anatomical pathologist: Molecular meets morphology.

In recent years anatomical pathology has been revolutionised by the incorporation of molecular findings into routine diagnostic practice, and in some diseases the presence of specific molecular alterations are nowessential for diagnosis. Spatial transcriptomics describes a group of technologies that provide up to transcriptome-wide expression profiling while preserving the spatial origin of the data, with many of these technologies able to provide these data using a single tissue section. Spatial transcriptomics allows expression profiling of highly specific areas within a tissue section potentially to subcellular resolution, and allows correlation of expression data with morphology, tissue type and location relative to other structures. While largely still research laboratory-based, several spatial transcriptomics methods have now achieved compatibility with formalin-fixed paraffin-embedded tissue (FFPE), allowing their use in diagnostic tissue samples, and with further development potentially leading to their incorporation in routine anatomical pathology practice. This mini review provides an overview of spatial transcriptomics methods, with an emphasis on platforms compatible with FFPE tissue, approaches to assess the data and potential applications in anatomical pathology practice.

Spatial distribution, ecological risk and origin of soil heavy metals in Laoguanhe watershed of China's South-to-North Water Diversion Middle Route Project

The central section of China's South-to-North Water Diversion Project has been designated as a national water conservation area, and the soil ecological security in its associated watersheds is of great importance. A total of 204 soil samples (0–20 cm depth) were obtained from the Laoguanhe River Basin. The concentrations of seven elements (Cd, Cr, Cu, Ni, Zn, Pb and Hg) were determined using inductively coupled plasma mass spectrometry and atomic fluorescence spectrometry following a near-total acid dissolution. Data analyses (including potential ecological risk, principal component analysis, geostatistical analysis and the positive matrix factorization model) were applied to evaluate the contamination of soil heavy metals and to identify their sources. The research results demonstrated that the mean contents of these seven elements exceeded background values for Henan Province, China, indicating human disturbance. Ecological risk evaluation revealed that Cd was the most frequently detected and the heavy metal causing the most pollution. Principal component analysis indicated that Cr, Ni and Cu stem from natural sources, while Zn and Cd are predominantly influenced by agricultural activities. Additionally, industrial activities and atmospheric deposition were responsible for the excess presence of Pb and Hg. The study suggests taking measures to control Cd sources in agricultural areas, reducing input of heavy metals into the river and providing scientific support for managing water quality.

Immune cell abundance and T cell receptor landscapes suggest new patient stratification strategies in head and neck squamous cell carcinoma.

Head and neck squamous cell carcinoma (HNSCC) is a molecularly and spatially heterogeneous disease frequently characterized by impairment of immunosurveillance mechanisms. Despite recent success with immunotherapy treatment, disease progression still occurs quickly after treatment in the majority of cases, suggesting the need to improve patient selection strategies. In the quest for biomarkers that may help inform response to checkpoint blockade, we characterized the tumour microenvironment (TME) of 162 HNSCC primary tumours of diverse aetiological and spatial origin, through gene expression and immunohistochemistry (IHC) profiling of relevant immune proteins, T cell receptor (TCR) repertoire analysis and whole-exome sequencing. We identified five HNSCC TME categories based on immune/stromal composition: (1) cytotoxic, (2) plasma cell rich, (3) dendritic cell rich, (4) macrophage rich and (5) immune-excluded. Remarkably, the cytotoxic and plasma cell rich subgroups exhibited a phenotype similar to tertiary lymphoid structures (TLS), which have been previously linked to immunotherapy response. We also found an increased richness of the TCR repertoire in these two subgroups and in never smokers. Mutational patterns evidencing APOBEC activity were enriched in the plasma cell high subgroup. Furthermore, specific signal propagation patterns within the Ras/ERK and PI3K/AKT pathways associated with distinct immune phenotypes. While traditionally CD8/CD3 T cell infiltration and immune checkpoint expression (e.g. PD-L1) have been used in the patient selection process for checkpoint blockade treatment, we suggest that additional biomarkers, such as TCR productive clonality, smoking history and TLS index, may have the ability to pull out potential responders to benefit from immunotherapeutic agents.

Variations in triple oxygen isotope of speleothems from the Asian monsoon region reveal moisture sources over the past 300 years

Characterization of moisture origins is crucial to understanding hydroclimatic processes. Nevertheless, documenting past atmospheric moisture contents and their sources remains challenging partially due to insufficient moisture-tracing proxies. Here, we present triple oxygen isotope compositions in 21 cave speleothems from monsoonal Asia to examine spatial moisture origin differences in eastern Asia over the past 300 years. Our data suggest an isotopic equilibrium fractionation during speleothem formation, and thus parent water 17O anomalies (Δ′17O) values reconstructed from speleothems preserve information on moisture origins and recycling across space. Notably, speleothem Δ′17O records exhibit a distinct geographical distribution, with low values in central-eastern and southern China, high values in northwestern and northern China, and relatively high values in the Yangtze River region. This spatial pattern underscores the diverse influence of different moisture sources regulated by regional hydrological circulation, and demonstrates the potential use of speleothem Δ′17O in reconstructing the moisture cycle at spatial scales.

Concentration, Spatial Distribution, and Source Analysis of Trace Elements in the Yarlung Zangbo River Basin and Its Two Tributaries

The Yarlung Zangbo River (YZR) is the longest plateau river in China and has famous tributaries, the Lhasa River and the Nianchu River. A total of 75 water samples were collected from the Yarlung Zangbo River Basin (YZRB) in this study to investigate the dissolved concentration, spatial distribution, and source of trace elements (Fe, V, Be, Ti, Mo, Se, Cd, Zn, Cu, Ni, Co, Mn, Cr, Ba, Tl, Pb, Hg, As, and Sb). The results indicate that only Cr and Tl contaminate water, while the other trace elements were in an unpolluted state. In addition, correlation analysis showed that there was a highly significant positive correlation between the concentrations of As, Sb, and Mo; there was also a highly significant positive correlation between the concentrations of Fe, Mn, Ti, Pb, Ni, Co, and Ba. The results of Positive Matrix Factorization (PMF) showed that there were four sources of trace elements in the YZRB, including the resuspension and dissolution of sediments (16.283%), agricultural source (11.436%), lithological source (47.418%), and soil-forming rocks (6.374%). Cluster analysis combined with PMF normalized contribution analysis, which showed that the trace elements found in the YZR’s mainstream were predominantly influenced by the surrounding rocks composition. Meanwhile, both the discharge of mining wastewater and sediments were marked in the Lhasa River. Additionally, agricultural activities were the chief contributors to the trace elements in the Nianchu River. Furthermore, the entire basin was subjected to the influence of soil-forming rocks. This study comprehensively analyzed and evaluated the physicochemical properties of water, the spatial distribution, and the pollution degree, and performed source analysis of trace elements in the YZRB. This research provides a foundational reference for further investigation of the spatial distribution and origins of trace elements in the rivers of the Qinghai–Tibet Plateau (QTP).

Cancer origin tracing and timing in two high-risk prostate cancers using multisample whole genome analysis: prospects for personalized medicine

BackgroundProstate cancer (PrCa) genomic heterogeneity causes resistance to therapies such as androgen deprivation. Such heterogeneity can be deciphered in the context of evolutionary principles, but current clinical trials do not include evolution as an essential feature. Whether or not analysis of genomic data in an evolutionary context in primary prostate cancer can provide unique added value in the research and clinical domains remains an open question.MethodsWe used novel processing techniques to obtain whole genome data together with 3D anatomic and histomorphologic analysis in two men (GP5 and GP12) with high-risk PrCa undergoing radical prostatectomy. A total of 22 whole genome-sequenced sites (16 primary cancer foci and 6 lymph node metastatic) were analyzed using evolutionary reconstruction tools and spatio-evolutionary models. Probability models were used to trace spatial and chronological origins of the primary tumor and metastases, chart their genetic drivers, and distinguish metastatic and non-metastatic subclones.ResultsIn patient GP5, CDK12 inactivation was among the first mutations, leading to a PrCa tandem duplicator phenotype and initiating the cancer around age 50, followed by rapid cancer evolution after age 57, and metastasis around age 59, 5 years prior to prostatectomy. In patient GP12, accelerated cancer progression was detected after age 54, and metastasis occurred around age 56, 3 years prior to prostatectomy. Multiple metastasis-originating events were identified in each patient and tracked anatomically. Metastasis from prostate to lymph nodes occurred strictly ipsilaterally in all 12 detected events. In this pilot, metastatic subclone content analysis appears to substantially enhance the identification of key drivers. Evolutionary analysis’ potential impact on therapy selection appears positive in these pilot cases.ConclusionsPrCa evolutionary analysis allows tracking of anatomic site of origin, timing of cancer origin and spread, and distinction of metastatic-capable from non-metastatic subclones. This enables better identification of actionable targets for therapy. If extended to larger cohorts, it appears likely that similar analyses could add substantial biological insight and clinically relevant value.

Dermomyotome-derived endothelial cells migrate to the dorsal aorta to support hematopoietic stem cell emergence.

Development of the dorsal aorta is a key step in the establishment of the adult blood-forming system, since hematopoietic stem and progenitor cells (HSPCs) arise from ventral aortic endothelium in all vertebrate animals studied. Work in zebrafish has demonstrated that arterial and venous endothelial precursors arise from distinct subsets of lateral plate mesoderm. Here, we profile the transcriptome of the earliest detectable endothelial cells (ECs) during zebrafish embryogenesis to demonstrate that tissue-specific EC programs initiate much earlier than previously appreciated, by the end of gastrulation. Classic studies in the chick embryo showed that paraxial mesoderm generates a subset of somite-derived endothelial cells (SDECs) that incorporate into the dorsal aorta to replace HSPCs as they exit the aorta and enter circulation. We describe a conserved program in the zebrafish, where a rare population of endothelial precursors delaminates from the dermomyotome to incorporate exclusively into the developing dorsal aorta. Although SDECs lack hematopoietic potential, they act as a local niche to support the emergence of HSPCs from neighboring hemogenic endothelium. Thus, at least three subsets of ECs contribute to the developing dorsal aorta: vascular ECs, hemogenic ECs, and SDECs. Taken together, our findings indicate that the distinct spatial origins of endothelial precursors dictate different cellular potentials within the developing dorsal aorta.

Gentrification and the Origin and Destination of Movers: A Systematic Review

AbstractGentrification is a process whereby neighbourhoods and their socio‐economic composition upgrade through residential moves and social mobility. Relatively little attention has been paid to the spatial aspect of gentrification‐induced residential moves. This systematic literature review focuses on the origin and destination of moves to and from gentrifying neighbourhoods, by gentrifiers (movers in) and displacees (movers out). It identifies where, when, and how such research has been conducted and highlights gaps in the literature. Our results suggest that the destination of displaced households has been studied extensively, while an understanding of the spatial origins of gentrifiers is lacking. The few studies dedicated to gentrifiers' origins mostly focus on intra‐urban environments, overlooking potential mobility dynamics from outside the city‐region. We highlight that capturing both origins and destinations of movers at different spatial scales is necessary to demonstrate how residential mobility creates interactions and demographic interdependencies between neighbourhoods and cities.