A conserved molecular logic for neurogenesis to gliogenesis switch in the cerebral cortex.

During development, neural stem cells in the cerebral cortex, also known as radial glial cells (RGCs), generate excitatory neurons, followed by production of cortical macroglia and inhibitory neurons that migrate to the olfactory bulb (OB). Understanding the mechanisms for this lineage switch is fundamental for unraveling how proper numbers of diverse neuronal and glial cell types are controlled. We and others recently showed that Sonic Hedgehog (Shh) signaling promotes the cortical RGC lineage switch to generate cortical oligodendrocytes and OB interneurons. During this process, cortical RGCs generate intermediate progenitor cells that express critical gliogenesis genes Ascl1, Egfr, and Olig2. The increased Ascl1 expression and appearance of Egfr+ and Olig2+ cortical progenitors are concurrent with the switch from excitatory neurogenesis to gliogenesis and OB interneuron neurogenesis in the cortex. While Shh signaling promotes Olig2 expression in the developing spinal cord, the exact mechanism for this transcriptional regulation is not known. Furthermore, the transcriptional regulation of Olig2 and Egfr has not been explored. Here, we show that in cortical progenitor cells, multiple regulatory programs, including Pax6 and Gli3, prevent precocious expression of Olig2, a gene essential for production of cortical oligodendrocytes and astrocytes. We identify multiple enhancers that control Olig2 expression in cortical progenitors and show that the mechanisms for regulating Olig2 expression are conserved between the mouse and human. Our study reveals evolutionarily conserved regulatory logic controlling the lineage switch of cortical neural stem cells.

Population genomics provides insights into the population structure and temperature-driven adaptation of Collichthys lucidus.

BACKGROUND: Understanding the genetic structure and local adaptive evolutionary mechanisms of marine organisms is crucial for the management of biological resources. As the ecologically and commercially important small-sized shallow-sea fish, Collichthys lucidus plays a vital role in the structure and functioning of marine ecosystem processes. C. lucidus has been shown to have an obvious population structure. Therefore, it is an ideal candidate for investigating population differentiation and local adaptation under heterogeneous environmental pressure. RESULTS: A total of 184,708 high-quality single nucleotide polymorphisms (SNPs) were identified and applied to elucidate the fine-scale genetic structure and local thermal adaptation of 8 C. lucidus populations. Population structure analysis based on all SNPs indicated that the northern group and southern group of C. lucidus have a strong differentiation. Moreover, 314 SNPs were found to be significantly associated with temperature variation, and annotations of genes containing temperature-related SNPs suggested that genes were involved in material (protein, lipid, and carbohydrate) metabolism and immune responses. CONCLUSION: The high genetic differentiation of 8 C. lucidus populations may have been caused by long-term geographic isolation during the glacial period. Moreover, we suspected that variation in these genes associated with material (protein, lipid, and carbohydrate) metabolism and immune responses was critical for adaptation to spatially heterogeneous temperatures in natural C. lucidus populations. In conclusion, this study could help us determine how C. lucidus populations will respond to future ocean temperature rising.

Radiomics analysis of apparent diffusion coefficient in cervical cancer: A preliminary study on histological grade evaluation.

BACKGROUND: The role of apparent diffusion coefficient (ADC)-based radiomics features in evaluating histopathological grade of cervical cancer is unresolved. PURPOSE: To determine if there is a difference between radiomics features derived from center-slice 2D versus whole-tumor volumetric 3D for ADC measurements in patients with cervical cancer regarding tumor histopathological grade, and systematically assess the impact of the b value on radiomics analysis in ADC quantifications. STUDY TYPE: Prospective. SUBJECTS: In all, 160 patients with histopathologically confirmed squamous cell carcinoma of uterine cervix. FIELD STRENGTH/SEQUENCE: Conventional and diffusion-weighted MR images (b values = 0, 800, 1000 s/mm2 ) were acquired on a 3.0T MR scanner. ASSESSMENT: Regions of interest (ROIs) were drawn manually along the margin of tumor on each slice, and then the center slice of the tumor was selected with naked eyes in the course of whole-tumor segmentation. A total of 624 radiomics features were derived from T2 -weighted images and ADC maps. We randomly selected 50 cases and did the reproducibility analysis. STATISTICAL TESTS: Parameters were compared using Wilcoxon signed rank test, Bland-Altman analysis, t-test, and least absolute shrinkage and selection operator (LASSO) regression with crossvalidation. RESULTS: In all, 95 radiomics features were insensitive to ROI variation among T2 images, ADC map of b800, and ADC map of b1000 (P > 0.0002). There was a significant statistical difference between the performances of 2D center-slice and 3D whole-tumor radiomics models in both ADC feature sets of b800 and b1000 (P < 0.0001, P < 0.0001). Compared with ADC features of b800 (0.3758 ± 0.0118), the model of b1000 ADC features appeared to be slightly lower in overall misclassification error (0.3642 ± 0.0162) (P = 0.0076). DATA CONCLUSION: Several radiomics features extracted from T2 images and ADC maps were highly reproducible. Whole-tumor volumetric 3D radiomics analysis had a better performance than using the 2D center-slice of tumor in stratifying the histological grade of cervical cancer. A b value of 1000 s/mm2 is suggested as the optimal parameter in pelvic DWI scans. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;49:280-290.

CT Features Associated with Epidermal Growth Factor Receptor Mutation Status in Patients with Lung Adenocarcinoma.

Purpose To retrospectively identify the relationship between epidermal growth factor receptor (EGFR) mutation status, predominant histologic subtype, and computed tomographic (CT) characteristics in surgically resected lung adenocarcinomas in a cohort of Asian patients. materials and Methods This study was approved by the institutional review board, with waiver of informed consent. Preoperative chest CT findings were retrospectively evaluated in 385 surgically resected lung adenocarcinomas. A total of 30 CT descriptors were assessed. EGFR mutations at exons 18-21 were determined by using the amplification refractory mutation system. Multiple logistic regression analyses were performed to identify independent factors of harboring EGFR mutation status. The final model was selected by using the backward elimination method, and two areas under the receiver operating characteristic curve (ROC) were compared with the nonparametric approach of DeLong, DeLong, and Clarke-Pearson. Results EGFR mutations were found in 168 (43.6%) of 385 patients. Mutations were found more frequently in (a) female patients (P < .001); (b)those who had never smoked (P < .001); (c)those with lepidic predominant adenocarcinomas (P = .001) or intermediate pathologic grade (P < .001); (e) smaller tumors (P < .001); (f)tumors with spiculation (P = .019), ground-glass opacity (GGO) or mixed GGO (P < .001), air bronchogram (P = .006), bubblelike lucency (P < .001), vascular convergence (P = .024), thickened adjacent bronchovascular bundles (P = .027), or pleural retraction (P < .001); and (g) tumors without pleural attachment (P = .004), a well-defined margin (P = .010), marked heterogeneous enhancement (P = .001), severe peripheral emphysema (P = .002), severe peripheral fibrosis (P = .013), or lymphadenopathy (P = .028). The most important and significantly independent prognostic factors of harboring EGFR-activating mutation for the model with both clinical variables and CT features were those who had never smoked and those with smaller tumors, bubblelike lucency, homogeneous enhancement, or pleural retraction when adjusting for histologic subtype, pathologic grade, or thickened adjacent bronchovascular bundles. ROC curve analysis showed that use of clinical variables combined with CT features (area under the ROC curve = 0.778) was superior to use of clinical variables alone (area under the ROC curve = 0.690). Conclusion CT imaging features of lung adenocarcinomas in combination with clinical variables can be used to prognosticate EGFR mutation status better than use of clinical variables alone. (©) RSNA, 2016 Online supplemental material is available for this article.

CT-imaging features of renal epithelioid angiomyolipoma.

BACKGROUND: The aim of this study was to describe the computed tomography (CT)-imaging features of renal epithelioid angiomyolipomas (E-AMLs) to understand and recognize this new category of renal tumors. METHODS: Institutional review board approval was obtained for this retrospective study. Clinical data and preoperative CT images of 11 cases of E-AML were retrospectively analyzed. All patients had unenhanced and tri-phase dynamic enhanced CT examination. CT-imaging features including tumor size, existence of fat and calcification, enhancement degree, enhancement pattern, and enhancement heterogeneity were evaluated. RESULTS: The patients were ten women and one man. The size of tumor ranged from 1.8 to 10.3 cm. All of them had distinct edges; one had a lobulated appearance, ten had bulging contour of the involved kidney, and four lesions had intratumoral fat. Eight of the E-AMLs demonstrated hyper-attenuation, two as iso-attenuation, and one as hypo-attenuation compared with renal parenchyma on unenhanced CT images. Contrast-enhanced CT features were markedly heterogeneous in eight cases (73 %). The predominant enhancement pattern was rapid wash-in to slow wash-out (91 %). CONCLUSIONS: The radiological appearance of most E-AMLs has a tendency to be hyper-attenuated on precontrast CT with or without fat component and demonstrates a rapid wash-in to slow wash-out dynamic enhancement pattern.

Spatial-temporal shifting patterns and in situ conservation of spotted seal (Phoca largha) populations in the Yellow Sea ecoregion.

Understanding the habitat shifting pattern is a prerequisite for implementing in situ conservation of migratory species. Spotted seals (Phoca largha) inhabiting the Yellow Sea ecoregion (YSE) comprise a small population with independent genes and represent a charismatic flagship species in this region. However, this population has declined by 80% since the 1940s, and increased support from the countries around the YSE is urgently needed to address the potential local extinction risk. A time-series niche model and life-history weighted systematic conservation planning were designed on the basis of a satellite beacon tracking survey (2010-2020) of the YSE population. The results showed clustering and spreading shifting patterns during the breeding and migratory seasons, respectively. The closed-loop migration route formed in the YSE indicated that this population might be geographically isolated from populations in other breeding areas around the world. The conservation priority area (CPA), with an area of 19 632 km2 (3.58% of the total YSE area), was the most effective response to the potential in situ risk. However, nearly 80% of the CPA was exposed outside the existing marine protected areas (MPAs). Future establishment of MPAs in China should strategically consider the conservation gap identified herein, and it is recommended for Korea's closed fishing season to be spatially set in the western Korean Peninsula from May to August. This study also exemplified that the lack of temporal information would lead to the dislocation of niche modeling for migratory species represented by spotted seals. Attention should be paid to protecting small and migratory populations in marine biodiversity conservation planning.

A genetic assessment of the population structure and demographic history of Odontamblyopuslacepedii (Perciformes, Amblyopinae) from the northwestern Pacific.

Coupled with geological and geographical history, climatic oscillations during the Pleistocene period had remarkable effects on species biodiversity and distribution along the northwestern Pacific. To detect the population structure and demographic history of Odontamblyopuslacepedii, 547-bp fragments of the mitochondrial DNA control region were sequenced. A low level of nucleotide diversity (0.0065 ± 0.0037) and a high level of haplotype diversity (0.98 ± 0.01) was observed. The Maximum Likelihood (ML) and Bayesian Inference phylogenetic trees showed no significant genealogical structure corresponding to sampling locations. The results of AMOVA and pairwise F ST values revealed some significant genetic differentiation among populations, and the isolation by distance (IBD) analysis supported that the genetic differentiation was associated with the geographic distances. The demographic history of O.lacepedii examined by neutrality tests, mismatch distribution analysis, and Bayesian Skyline Plots (BSP) analysis suggested a sudden population expansion, and the expansion time was estimated to be around the Pleistocene. We hypothesize that the climate changes during the Pleistocene, ocean currents, and larval dispersal capabilities have played an important role in shaping contemporary phylogeographic pattern and population structure of O.lacepedii.

Natural distinction of carbon and nitrogen isotopic niches in common fish species across marine biotopes in the Yellow River estuary.

Stable isotope analysis is a universally recognized and efficient method of indicating trophic relationships that is widely applied in research. However, variation in stable isotope ratios may lead to inaccuracies due to the effects of complex environmental conditions. This research compared the carbon and nitrogen isotopic niches of fish communities between diverse biotopes around the Yellow River estuary and adjacent sea areas, with the aim of revealing distinctions in stable isotopic niche metrics, trophic positions, and feeding preferences. Our analysis of the food source contribution indicated that allochthonous sources were considered major energy sources in estuarine areas directly affected by Yellow River-diluted water, while autochthonous benthic and pelagic producers dominated carbon input into the food web in Laizhou Bay and the open water. A significant variation in the fish δ15N characteristic was found within estuarine adjacent regions, so, together with the results from previous studies, we deemed the local high concentration of dissolved inorganic nitrogen as the original trigger of the abnormal δ15N characteristic in fishes via a transport process along food chains. These results provide a new perspective on the natural distinction of carbon and nitrogen isotopic niches. The detailed data reported here enhance our understanding of variations in fish communities in estuarine ecosystems.

A non-exhaustive survey revealed possible genetic similarity in mitochondrial adaptive evolution of marine fish species in the northwestern Pacific.

Mitochondrial coding genes involved in the oxidative phosphorylation pathway play vitally important roles in energy production and thermal adaptation. Investigating the underlying molecular mechanism of mitochondrial adaptive evolution is crucial for understanding biodiversity and ecological radiation. In this study, we collated population genetic studies of marine fish species in the northwestern Pacific based on mitochondrial cytochrome b gene sequences, to investigate whether similar patterns could be detected in mitochondrial adaptive evolution. After filtering, nine studies containing eight marine fish species (Ammodytes personatus, Boleophthalmus pectinirostris, Larimichthys polyactis, Mugil cephalus, Pampus argenteus, Platycephalus sp.1, Sebastiscus marmoratus, and Trachidermus fasciatus) belonging to eight different families were retained. Multiple codon-based approaches were used to identify potential sites under selection in each species. By comparison, our results showed that the posterior part of the mitochondrial cytochrome b gene (particularly codon 372 and its neighboring sites) seemed to be involved in the adaptive evolution process, suggesting potential genetic similarity among distantly related species. We also summarized four types of adaptive patterns in the reviewed species, and suggest that the level of genetic differentiation and mitochondrial adaptive evolution might be correlated. Further studies are needed to confirm such relationship by detecting RNA-level evidence and investigating more species and samples.

ROS-mediated programmed cell death (PCD) of Thalassiosira pseudonana under the stress of BDE-47.

Polybrominated diphenyl ethers (PBDEs) are a series of highly persistent organic pollutants (POPs) ubiquitously distributed in marine environments. As key primary producers, microalgae are the start of PBDEs bioaccumulations and vulnerable to their toxicities. In order to deeply investigate the toxic mechanism of PBDEs on microalgal cells, the occurrence of programmed cell death (PCD) in a model diatom Thalassiosira pseudonana and its possible mediating mechanism were studied. The results indicated: cell death of T. pseudonana happened under the stress of BDE-47, which was proved to be PCD based on the correlations with three biochemical markers (DNA fragmentation, phosphatidylserine externalization and caspase activity) and three molecular markers [Metacaspase 2 gene (TpMC2), Death-associated protein gene (DAP3) and Death-specific protein 1 gene (TpDSP1)]; Furthermore, the changes of cellular ROS levels were correlated with the PCD markers and the dead cell rates, and the cell membrane and the chloroplast were identified as the major ROS production sites. Therefore, we concluded that PCD might be an important toxic mechanism of PBDEs on microalgal cells, and that chloroplast- and cell membrane-produced ROS was an important signaling molecule to mediate the PCD activation process. Our research firstly indicated microalgal PCD could be induced by PBDEs, and increased our knowledge of the toxic mechanisms by which POPs affect microalgal cells.

Prediction of pathological nodal involvement by CT-based Radiomic features of the primary tumor in patients with clinically node-negative peripheral lung adenocarcinomas.

PURPOSE: The purpose of this study was to investigate the potential of computed tomography (CT) based radiomic features of primary tumors to predict pathological nodal involvement in clinically node-negative (N0) peripheral lung adenocarcinomas. METHODS: A total of 187 patients with clinical N0 peripheral lung adenocarcinomas who underwent preoperative CT scan and subsequently received systematic lymph node dissection were retrospectively reviewed. 219 quantitative 3D radiomic features of primary lung tumor were extracted; meanwhile, nine radiological semantic features were evaluated. Univariate and multivariate logistic regression analysis were used to explore the role of these features in predicting pathological nodal involvement. The areas under the ROC curves (AUCs) were compared between multivariate logistic regression models. RESULTS: A total of 153 patients had pathological N0 status and 34 had pathological lymph node metastasis. On univariate analysis, fissure attachment and 17 radiomic features were significantly associated with pathological nodal involvement. Multivariate analysis revealed that semantic features of pleural retraction (P = 0.048) and fissure attachment (P = 0.023) were significant predictors of pathological nodal involvement (AUC = 0.659); and the radiomic feature F185 (Histogram SD Layer 1) (P = 0.0001) was an independent prognostic factor of pathological nodal involvement (AUC = 0.73). A logistic regression model produced from combining radiomic feature and semantic feature showed the highest AUC of 0.758 (95% CI: 0.685-0.831), and the AUC value computed by fivefold cross-validation method was 0.737 (95% CI: 0.73-0.744). CONCLUSIONS: Features derived on primary lung tumor described by semantic and radiomic could provide information of pathological nodal involvement in clinical N0 peripheral lung adenocarcinomas.

Tumor heterogeneity assessed by texture analysis on contrast-enhanced CT in lung adenocarcinoma: association with pathologic grade.

Objectives To investigate whether texture features on contrast-enhanced computed tomography (CECT) images of lung adenocarcinoma have association with pathologic grade. Methods A cohort of 148 patients with surgically operated adenocarcinoma was retrospectively reviewed. Fifty-four CT features of the primary lung tumor were extracted from CECT images using open-source 3D Slicer software; meanwhile, enhancement homogeneity was evaluated by two radiologists using visual assessment. Multivariate logistic regression analysis was performed to determine significant image indicator of pathologic grade. Results Tumors of intermediate grade were more likely to be never smokers (P=0.020). Enhancement heterogeneity by visual assessment showed no statistical difference between intermediate grade and high grade (P=0.671). Among those 54 features, 29 of them were significantly associated with pathologic grade. Multivariate logistic regression analyses identified F33 (Homogeneity 1) (P=0.005) and F38 (Inverse Variance) (P=0.032) as unique independent image indicators of pathologic grade, and the AUC calculated from this model (AUC=0.834) was higher than clinical model (AUC=0.615) (P=0.0001). Conclusions Our study revealed that texture analysis on CECT images could be helpful in predicting pathologic grade of lung adenocarcinoma.

Associations between radiologist-defined semantic and automatically computed radiomic features in non-small cell lung cancer.

Tumor phenotypes captured in computed tomography (CT) images can be described qualitatively and quantitatively using radiologist-defined "semantic" and computer-derived "radiomic" features, respectively. While both types of features have shown to be promising predictors of prognosis, the association between these groups of features remains unclear. We investigated the associations between semantic and radiomic features in CT images of 258 non-small cell lung adenocarcinomas. The tumor imaging phenotypes were described using 9 qualitative semantic features that were scored by radiologists, and 57 quantitative radiomic features that were automatically calculated using mathematical algorithms. Of the 9 semantic features, 3 were rated on a binary scale (cavitation, air bronchogram, and calcification) and 6 were rated on a categorical scale (texture, border definition, contour, lobulation, spiculation, and concavity). 32-41 radiomic features were associated with the binary semantic features (AUC = 0.56-0.76). The relationship between all radiomic features and the categorical semantic features ranged from weak to moderate (|Spearmen's correlation| = 0.002-0.65). There are associations between semantic and radiomic features, however the associations were not strong despite being significant. Our results indicate that radiomic features may capture distinct tumor phenotypes that fail to be perceived by naked eye that semantic features do not describe and vice versa.

Global patterns and predictions of seafloor biomass using random forests.

A comprehensive seafloor biomass and abundance database has been constructed from 24 oceanographic institutions worldwide within the Census of Marine Life (CoML) field projects. The machine-learning algorithm, Random Forests, was employed to model and predict seafloor standing stocks from surface primary production, water-column integrated and export particulate organic matter (POM), seafloor relief, and bottom water properties. The predictive models explain 63% to 88% of stock variance among the major size groups. Individual and composite maps of predicted global seafloor biomass and abundance are generated for bacteria, meiofauna, macrofauna, and megafauna (invertebrates and fishes). Patterns of benthic standing stocks were positive functions of surface primary production and delivery of the particulate organic carbon (POC) flux to the seafloor. At a regional scale, the census maps illustrate that integrated biomass is highest at the poles, on continental margins associated with coastal upwelling and with broad zones associated with equatorial divergence. Lowest values are consistently encountered on the central abyssal plains of major ocean basins The shift of biomass dominance groups with depth is shown to be affected by the decrease in average body size rather than abundance, presumably due to decrease in quantity and quality of food supply. This biomass census and associated maps are vital components of mechanistic deep-sea food web models and global carbon cycling, and as such provide fundamental information that can be incorporated into evidence-based management.