RASopathies for Radiologists.

RASopathies are a heterogeneous group of genetic syndromes caused by germline mutations in a group of genes that encode components or regulators of the Ras/mitogen-activated protein kinase (MAPK) signaling pathway. RASopathies include neurofibromatosis type 1, Legius syndrome, Noonan syndrome, Costello syndrome, cardiofaciocutaneous syndrome, central conducting lymphatic anomaly, and capillary malformation-arteriovenous malformation syndrome. These disorders are grouped together as RASopathies based on our current understanding of the Ras/MAPK pathway. Abnormal activation of the Ras/MAPK pathway plays a major role in development of RASopathies. The individual disorders of RASopathies are rare, but collectively they are the most common genetic condition (one in 1000 newborns). Activation or dysregulation of the common Ras/MAPK pathway gives rise to overlapping clinical features of RASopathies, involving the cardiovascular, lymphatic, musculoskeletal, cutaneous, and central nervous systems. At the same time, there is much phenotypic variability in this group of disorders. Benign and malignant tumors are associated with certain disorders. Recently, many institutions have established multidisciplinary RASopathy clinics to address unique therapeutic challenges for patients with RASopathies. Medications developed for Ras/MAPK pathway-related cancer treatment may also control the clinical symptoms due to an abnormal Ras/MAPK pathway in RASopathies. Therefore, radiologists need to be aware of the concept of RASopathies to participate in multidisciplinary care. As with the clinical manifestations, imaging features of RASopathies are overlapping and at the same time diverse. As an introduction to the concept of RASopathies, the authors present major representative RASopathies, with emphasis on their imaging similarities and differences. ©RSNA, 2024 Test Your Knowledge questions for this article are available in the supplemental material.

Urologic Presentation of Unicentric Pediatric Castleman Disease in the Setting of Acute Renal Colic.

An 11-year-old otherwise healthy female presented with renal colic and during computed tomography imaging evaluation, she was found to have a right distal ureteral stone with associated hydroureteronephrosis, medially deviated ureter, and 4-cm solid retroperitoneal mass. The mass was palpable on physical exam and was further categorized with magnetic resonance imaging, ultrasound, and laboratory testing. A multidisciplinary team approach, including pediatric surgery, radiology, oncology, and urology, led to the patient undergoing a right retrograde pyelogram, ureteroscopy with stent placement, and laparoscopic excision of retroperitoneal mass. Her pathology revealed lymphoid hyperplasia with histologic features of Castleman disease.

Transcriptome analysis of rice root tips reveals auxin, gibberellin, and ethylene signalling underlying nutritropism.

Nutritropism is a positive tropism towards nutrients in plant roots. An NH4+ gradient is a nutritropic stimulus in rice (Oryza sativa L.). When rice roots are exposed to an NH4+ gradient generated around nutrient sources, root tips bend towards and coil around the sources. The molecular mechanisms are largely unknown. Here, we analysed the transcriptomes of the inside and outside of bending root tips exhibiting nutritropism to reveal nutritropic signal transduction. Tissues facing the nutrient sources (inside) and away (outside) were separately collected by laser microdissection. Principal component analysis revealed distinct transcriptome patterns between the two tissues. Annotations of 153 differentially expressed genes implied that auxin, gibberellin, and ethylene signalling were activated differentially between the sides of the root tips under nutritropism. Exogenous application of transport and/or biosynthesis inhibitors of these phytohormones largely inhibited the nutritropism. Thus, signalling and de novo biosynthesis of the three phytohormones is necessary for nutritropism. Expression patterns of IAA genes implied that auxins accumulated more in the inside tissues, meaning that ammonium stimulus is transduced to auxin signalling in nutritropism as same as gravity stimulus in gravitropism. SAUR and expansin genes, which are known to control cell wall modification and to promote cell elongation in shoot gravitropism, were highly expressed in the inside tissues rather than the outside tissues, and our transcriptome data are unexplainable for differential elongation in root nutritropism.

Neuroimaging of Neonatal Stroke: Venous Focus.

Perinatal venous infarcts are underrecognized clinically and at imaging. Neonates may be susceptible to venous infarcts because of hypercoagulable state, compressibility of the dural sinuses and superficial veins due to patent sutures, immature cerebral venous drainage pathways, and drastic physiologic changes of the brain circulation in the perinatal period. About 43% of cases of pediatric cerebral sinovenous thrombosis occur in the neonatal period. Venous infarcts can be recognized by ischemia or hemorrhage that does not respect an arterial territory. Knowledge of venous drainage pathways and territories can help radiologists recognize characteristic venous infarct patterns. Intraventricular hemorrhage in a term neonate with thalamocaudate hemorrhage should raise concern for internal cerebral vein thrombosis. A striato-hippocampal pattern of hemorrhage indicates basal vein of Rosenthal thrombosis. Choroid plexus hemorrhage may be due to obstruction of choroidal veins that drain the internal cerebral vein or basal vein of Rosenthal. Fan-shaped deep medullary venous congestion or thrombosis is due to impaired venous drainage into the subependymal veins, most commonly caused by germinal matrix hemorrhage in the premature infant and impeded flow in the deep venous system in the term infant. Subpial hemorrhage, an underrecognized hemorrhage stroke type, is often observed in the superficial temporal region, and its cause is probably multifactorial. The treatment of cerebral sinovenous thrombosis is anticoagulation, which should be considered even in the presence of intracranial hemorrhage. ©RSNA, 2024 Test Your Knowledge questions in the supplemental material and the slide presentation from the RSNA Annual Meeting are available for this article.

MiRiQ Database: A Platform for In Silico Rice Mutant Screening.

Genetic studies using mutant resources have significantly contributed to elucidating plant gene function. Massive mutant libraries sequenced by next-generation sequencing technology facilitate mutant identification and functional analysis of genes of interest. Here, we report the creation and release of an open-access database (https://miriq.agr.kyushu-u.ac.jp/index.php), called Mutation-induced Rice in Kyushu University (MiRiQ), designed for in silico mutant screening based on a whole-genome-sequenced mutant library. This database allows any user to easily find mutants of interest without laborious efforts such as large-scale screening by PCR. The initial version of the MiRiQ database (version 1.0) harbors a total of 1.6 million single-nucleotide variants (SNVs) and InDels of 721 M1 plants that were mutagenized by N-methyl-N-nitrosourea treatment of the rice cultivar Nipponbare (Oryza sativa ssp. japonica). The SNVs were distributed among 87% of all 35,630 annotated protein-coding genes of the Nipponbare genome and were predicted to induce missense and nonsense mutations. The MiRiQ database provides built-in tools, such as a search tool by keywords and JBrowse for mutation searches. Users can request mutant seeds in the M2 or M3 generations from a request form linked to this database. We believe that the availability of a wide range of gene mutations in this database will benefit the plant science community and breeders worldwide by accelerating functional genomic research and crop improvement.

Pediatric focal calvarial lesions: an illustrated review.

Focal skull lesions in children can be diagnostically challenging with a wide variety of potential etiologies. Understanding the diverse pathologies and recognizing their associated clinical and imaging characteristics is crucial for accurate diagnosis and appropriate treatment planning. We review pertinent anatomy of the scalp and calvarium and review different pathologies that can present with focal skull lesions in pediatric patients. These include neoplastic, non-neoplastic tumor-like, congenital, post traumatic, and vascular-associated etiologies. We review the key clinical and imaging features associated with these pathologies and present teaching points to help make the correct diagnosis. It is important for radiologists to be aware of the common and rare etiologies of skull lesions as well as the clinical and imaging characteristics which can be used to develop an accurate differential to ensure a timely diagnosis and initiate appropriate management.

Designing rice panicle architecture via developmental regulatory genes.

Rice panicle architecture displays remarkable diversity in branch number, branch length, and grain arrangement; however, much remains unknown about how such diversity in patterns is generated. Although several genes related to panicle branch number and panicle length have been identified, how panicle branch number and panicle length are coordinately regulated is unclear. Here, we show that panicle length and panicle branch number are independently regulated by the genes Prl5/OsGA20ox4, Pbl6/APO1, and Gn1a/OsCKX2. We produced near-isogenic lines (NILs) in the Koshihikari genetic background harboring the elite alleles for Prl5, regulating panicle rachis length; Pbl6, regulating primary branch length; and Gn1a, regulating panicle branching in various combinations. A pyramiding line carrying Prl5, Pbl6, and Gn1a showed increased panicle length and branching without any trade-off relationship between branch length or number. We successfully produced various arrangement patterns of grains by changing the combination of alleles at these three loci. Improvement of panicle architecture raised yield without associated negative effects on yield-related traits except for panicle number. Three-dimensional (3D) analyses by X-ray computed tomography (CT) of panicles revealed that differences in panicle architecture affect grain filling. Importantly, we determined that Prl5 improves grain filling without affecting grain number.

A leaf-emanated signal orchestrates grain size and number in response to maternal resources.

In plants, variations in seed size and number are outcomes of different reproductive strategies. Both traits are often environmentally influenced, suggesting that a mechanism exists to coordinate these phenotypes in response to available maternal resources. Yet, how maternal resources are sensed and influence seed size and number is largely unknown. Here, we report a mechanism that senses maternal resources and coordinates grain size and number in the wild rice Oryza rufipogon, a wild progenitor of Asian cultivated rice. We showed that FT-like 9 (FTL9) regulates both grain size and number and that maternal photosynthetic assimilates induce FTL9 expression in leaves to act as a long-range signal that increases grain number and reduces size. Our findings highlight a strategy that benefits wild plants to survive in a fluctuating environment. In this strategy, when maternal resources are sufficient, wild plants increase their offspring number while preventing an increase in offspring size by the action of FTL9, which helps expand their habitats. In addition, we found that a loss-of-function allele (ftl9) is prevalent among wild and cultivated populations, offering a new scenario in the history of rice domestication.

Ventriculus terminalis cyst in an infant: a case report.

BACKGROUND: Filar cysts are frequently found on neonatal ultrasound and are physiologically involuting structures with natural resolution. Hence, there has been no previous histologic correlation. Ventriculus terminalis is a focal central canal dilation in the conus medullaris and usually not clinically significant. Extra-axial cyst at the conus-filum junction connected to ventriculus terminalis is extremely rare, especially when associated with tethered lipomatous filum terminale and with progressive cyst enlargement. CASE PRESENTATION: A Caucasian female neonate with abnormal gluteal cleft had ventriculus terminalis cyst with an extra-axial cyst at the conus-filar junction and taut lipomatous filum on ultrasound examination and magnetic resonance imaging. This persisted at 6-month follow up imaging. In light of the nonresolving extra-axial mass and thick taut lipomatous filum, the child underwent L1-L3 osteoplastic laminectomies. The extra-axial cyst expanded after bony decompression and furthermore on dural opening; visualized on ultrasound. It communicated with the central canal and was documented with intraoperative photomicrographs. It was excised and filum sectioned. Histological immunostaining of the cyst wall showed neuroglial and axonal elements. The child did well without deficits at 4-year follow up with normal urodynamics. CONCLUSION: Progression dilation of ventriculus terminalis and extra-axial conofilar cyst with tethered lipomatous filum will likely progress to clinical significance and require surgical intervention. The embryologic basis for this pathology is discussed, with literature review.

Control of Plant Cell Growth and Proliferation by MO25A, a Conserved Major Component of the Mammalian Sterile 20-Like Kinase Pathway.

The precise control of cell growth and proliferation underpins the development of plants and animals. These factors affect the development and size of organs and the body. In plants, the growth and proliferation of cells are regulated by environmental stimuli and intrinsic signaling, allowing different cell types to have specific growth and proliferation characteristics. An increasing number of factors that control cell division and growth have been identified. However, the mechanisms underlying cell type-specific cell growth and proliferation characteristics in the normal developmental context are poorly understood. Here, we analyzed the rice mutant osmo25a1, which is defective in the progression of embryogenesis. The osmo25a1 mutant embryo developed incomplete embryonic organs, such as the shoot and root apical meristems. It showed a delayed progression of embryogenesis, associated with the reduced mitotic activity. The causal gene of this mutation encodes a member of the Mouse protein-25A (MO25A) family of proteins that have pivotal functions in a signaling pathway that governs cell proliferation and polarity in animals, yeasts and filamentous fungi. To elucidate the function of plant MO25A at the cellular level, we performed a functional analysis of MO25A in the moss Physcomitrium patens. Physcomitrium patens MO25A was uniformly distributed in the cytoplasm and functioned in cell tip growth and the initiation of cell division in stem cells. Overall, we demonstrated that MO25A proteins are conserved factors that control cell proliferation and growth.

Post-embryonic function of GLOBULAR EMBRYO 4 (GLE4)/OsMPK6 in rice development.

In plants, mitogen activated protein kinases (MPKs) are involved in various signaling pathways that lead to biotic and abiotic responses as well as that regulate developmental processes. Among them, MPK6 and its closely related homologue, MPK3, act redundantly and are known to be involved in asymmetric cell divisions of meristemoid mother cells in stomata development and of zygotes in Arabidopsis. Loss-of-function mutants of GLE4/OsMPK6, which is an orthologue of MPK6 in rice, showed a defect in polarity establishment in early stage of embryogenesis. However, because of the embryo lethality of the mutations, the function of GLE4/OsMPK6 in post-embryonic development is not clarified. Here, we report the analysis of post embryonic function of GLE4/OsMPK6 in vegetative stage of rice using regenerated gle4/osmpk6 homozygous plants from tissue culture. The regenerated plants are dwarf and produce multiple shoots with small leaves. These shoots never develop into reproductive stage, instead, proliferate vegetative shoots repeatedly. Leaves of gle4/osmpk6 have small leaf blade at the tip and blade-sheath boundary become obscure. Stomata arrangement is also disturbed in gle4/osmpk6 leaf blade. The shape of shoot apical meristem of gle4/osmpk6 become disorganized. Thus, GLE4/OsMPK6 functions in shoot organization and stomata patterning in the post embryonic development in rice.

Measurements of Antibacterial Activity of Seed Crude Extracts in Cultivated Rice and Wild Oryza Species.

Seeds are continuously exposed to a wide variety of microorganisms in the soil. In addition, seeds contain large amounts of carbon and nitrogen sources that support initial growth after germination. Thus, seeds in the soil can easily promote microbial growth, and seeds are susceptible to decay. Therefore, seed defense against microorganisms is important for plant survival. Seed-microbe interactions are also important issues from the perspective of food production, in seed quality and shelf life. However, seed-microbe interactions remain largely unexplored. In this study, we established a simple and rapid assay system for the antibacterial activity of rice seed crude extracts by colorimetric quantification methods by the reduction of tetrazolium compound. Using this experimental system, the diversity of effects of rice seed extracts on microbial growth was analyzed using Escherichia coli as a bacterial model. We used collections of cultivated rice, comprising 50 accessions of Japanese landraces, 52 accessions of world rice core collections, and of 30 wild Oryza accessions. Furthermore, we attempted to find genetic factors responsible for the diversity by genome-wide association analysis. Our results demonstrate that this experimental system can easily analyze the effects of seed extracts on bacterial growth. It also suggests that there are various compounds in rice seeds that affect microbial growth. Overall, this experimental system can be used to clarify the chemical entities and genetic control of seed-microbe interactions and will open the door for understanding the diverse seed-microbe interactions through metabolites.

Whole-Genome Sequencing of Rice Mutant Library Members Induced by N-Methyl-N-Nitrosourea Mutagenesis of Fertilized Egg Cells.

Although targeted genome editing technology has become a powerful reverse genetic approach for accelerating functional genomics, conventional mutant libraries induced by chemical mutagens remain valuable for plant studies. Plants containing chemically induced mutations are simple yet effective genetic tools that can be grown without regard for biosafety issues. Whole-genome sequencing of mutant individuals reduces the effort required for mutant screening, thereby increasing their utility. In this study, we sequenced members of a mutant library of Oryza sativa cv. Nipponbare derived from treating single fertilized egg cells with N-methyl-N-nitrosourea (MNU). By whole-genome sequencing 266 M1 plants in this mutant library, we identified a total of 0.66 million induced point mutations. This result represented one mutation in every 146-kb of genome sequence in the 373 Mb assembled rice genome. These point mutations were uniformly distributed throughout the rice genome, and over 70,000 point mutations were located within coding sequences. Although this mutant library was a small population, nonsynonymous mutations were found in nearly 61% of all annotated rice genes, and 8.6% (3248 genes) had point mutations with large effects on gene function, such as gaining a stop codon or losing a start codon. WGS showed MNU-mutagenesis using rice fertilized egg cells induces mutations efficiently and is suitable for constructing mutant libraries for an in silico mutant screening system. Expanding this mutant library and its database will provide a useful in silico screening tool that facilitates functional genomics studies with a special emphasis on rice.

Measurements of the number of specified and unspecified cells in the shoot apical meristem during a plastochron in rice (Oryza sativa) reveal the robustness of cellular specification process in plant development.

The shoot apical meristem (SAM) is composed of a population of stem cells giving rise to the aboveground parts of plants. It maintains itself by controlling the balance of cell proliferation and specification. Although knowledge of the mechanisms maintaining the SAM has been accumulating, the processes of cellular specification to form leaves and replenishment of unspecified cells in the SAM during a plastochron (the time interval between which two successive leaf primordia are formed) is still obscure. In this study, we developed a method to quantify the number of specified and unspecified cells in the SAM and used it to elucidate the dynamics of cellular specification in the SAM during a plastochron in rice. OSH1 is a KNOX (KNOTTED1-like homeobox) gene in rice that is expressed in the unspecified cells in the SAM, but not in specified cells. Thus, we could visualize and count the nuclei of unspecified cells by fluorescent immunohistochemical staining with an anti-OSH1 antibody followed by fluorescein isothiocyanate detection. By double-staining with propidium iodide (which stains all nuclei) and then overlaying the images, we could also detect and count the specified cells. By using these measurements in combination with morphological observation, we defined four developmental stages of SAM that portray cellular specification and replenishment of unspecified cells in the SAM during a plastochron. In addition, through the analysis of mutant lines with altered size and shape of the SAM, we found that the number of specified cells destined to form a leaf primordium is not affected by mild perturbations of meristem size and shape. Our study highlights the dynamism and flexibility in stem cell maintenance in the SAM during a plastochron and the robustness of plant development.

Measuring Factor XIII Inhibitors in Patients with Factor XIII Deficiency: A Case Report and Systematic Review of Current Practices in Japan.

Factor XIII (FXIII) deficiency is a rare but serious coagulopathy. FXIII is critical in blood coagulation, and FXIII deficiencies can lead to uncontrolled or spontaneous bleeding. FXIII deficiencies can be congenital or acquired; acquired FXIII deficiency can be categorized as autoimmune and non-autoimmune. Immunological tests to measure FXIII inhibitors are required to diagnose acquired FXIII deficiency; however, appropriate test facilities are limited, which increases the turnaround time of these tests. In the case of critical bleeding, delayed test results may worsen prognosis due to delayed treatment. Here, we report a case of acquired FXIII deficiency, followed by a review of FXIII deficiency cases in Japan. We performed a systematic review to investigate the present conditions of the diagnosis and treatment of FXIII deficiency, including the measurement of FXIII inhibitors in Japan. FXIII inhibitor testing was only performed in 29.7 of acquired FXIII deficiency cases. Clinical departments other than internal medicine and pediatrics were often involved in medical treatment at the time of onset. Therefore, it is important for doctors in clinical departments other than internal medicine and pediatrics to consider FXIII deficiency and perform FXIII inhibitor testing when examining patients with prolonged bleeding of unknown cause or persistent bleeding after trauma.

Transcriptome and hyperspectral profiling allows assessment of phosphorus nutrient status in rice under field conditions.

Phosphorus (P) is one of the macronutrients indispensable for crop production, and therefore it is important to understand the potential of plants to adapt to low P conditions. We compared growth and leaf genome-wide transcriptome of four rice cultivars during growth between two fields with different amount of available phosphate and further analysed the acceptable range of P levels for normal growth from the view of both appearance traits and internal P nutrient status, which was measured by profiling the expression of the P indicator gene. This demonstrated that rice plants have a robustness to moderate P-deficient conditions expressing a system for P acquisition and usage without any effects on yield potential and that P indicator gene expression could be a useful index for early diagnosis of P status in plants. To develop a simple method for assessment of P status, we tried to predict the expression level using reflectance spectroscopy and hyperspectral imaging, thereby providing models with good performance. Our findings suggest that rice plants have the potential to adapt to moderate low P conditions in the field and showed that the hyperspectral technique is one of the useful tools for simple measurement of molecular-level dynamics reflecting internal nutrient conditions.

Temporal changes in transcripts of miniature inverted-repeat transposable elements during rice endosperm development.

The repression of transcription from transposable elements (TEs) by DNA methylation is necessary to maintain genome integrity and prevent harmful mutations. However, under certain circumstances, TEs may escape from the host defense system and reactivate their transcription. In Arabidopsis (Arabidopsis thaliana) and rice (Oryza sativa), DNA demethylases target the sequences derived from TEs in the central cell, the progenitor cell for the endosperm in the female gametophyte. Genome-wide DNA demethylation is also observed in the endosperm after fertilization. In the present study, we used a custom microarray to survey the transcripts generated from TEs during rice endosperm development and at selected time points in the embryo as a control. The expression patterns of TE transcripts are dynamically up- and downregulated during endosperm development, especially those of miniature inverted-repeat TEs (MITEs). Some TE transcripts were directionally controlled, whereas the other DNA transposons and retrotransposons were not. We also discovered the NUCLEAR FACTOR Y binding motif, CCAAT, in the region near the 5' terminal inverted repeat of Youren, one of the transcribed MITEs in the endosperm. Our results uncover dynamic changes in TE activity during endosperm development in rice.

NARROW AND DWARF LEAF 1, the Ortholog of Arabidopsis ENHANCER OF SHOOT REGENERATION1/DORNRÖSCHEN, Mediates Leaf Development and Maintenance of the Shoot Apical Meristem in Oryza sativa L.

The molecular basis for leaf development, a major focus in developmental biology, remains unclear in the monocotyledonous grass, rice (Oryza sativa). Here, we performed a mutant screen in rice and identified an AP2-type transcription factor family protein, NARROW AND DWARF LEAF1 (NDL1). NDL1 is the ortholog of Arabidopsis thaliana (subsequently called Arabidopsis) ENHANCER OF SHOOT REGENERATION1 (ESR1)/DORNRÖSCHEN (DRN) and mediates leaf development and maintenance of the shoot apical meristem (SAM). Loss of function of NDL1 results in bladeless leaves and SAMs that are flat, rather than dome-shaped, and lack cell proliferation activity. This loss of function also causes reduced auxin signaling. Moreover, as is the case with Arabidopsis ESR1/DRN, NDL1 plays crucial roles in shoot regeneration. Importantly, we found that NDL1 is not expressed in the SAM but is expressed in leaf primordia. We propose that NDL1 cell autonomously regulates leaf development, but non-cell autonomously regulates SAM maintenance in rice.