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Nonsyndromic hereditary thoracic aortic aneurysm and dissection (TAAD) is an autosomal dominant disease; however, it is frequently difficult to identify the causative genes. We report in this study a 33‐year‐old Japanese male with TAAD (Stanford type A) that is complicated with severe aortic regurgitation. There was no family history of aortic diseases in the patient nor any specific clinical features suggestive of connective tissue diseases, such as Marfan syndrome. Genetic testing identified candidate causative variants in two different genes: MYLK (c.4819G > A, p.[Gly1607Ser]) and FBN1 (c.365G > A, p.[Arg122His]). Familial cosegregation analysis revealed that the novel de novo MYLK variant was present only in the proband, and the FBN1 variant was also found in his nonaffected mother, and thus the MYLK variant was classified as likely pathogenic. MYLK is a causative gene for nonsyndromic TAAD that requires careful management; however, the number of reports is limited. Accumulating data on the pathogenicity of rare variants by performing a comprehensive pedigree analysis would help establish better treatment strategies for life‐threatening hereditary TAAD cases. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Genetic variants associated with hereditary TAAD may contribute to nonsyndromic TAAD. We present the case of a 72‐year‐old man with nonsyndromic TAAD undergoing prophylactic surgery after a gene panel test revealed a pathogenic variant in TGFBR1, but the indication for genetic testing in such elderly‐onset cases still warrants further discussion. Hereditary thoracic aortic aneurysm and dissection (TAAD) is a serious clinical condition resulting in a fatal outcome. Recently, variants in causative genes for syndromic hereditary TAAD, such as Marfan syndrome and Loeys–Dietz syndrome (LDS), have been reported to predispose to the development of nonsyndromic TAAD; however, genetic testing for patients with elderly‐onset nonsyndromic TAAD warrants further discussion. We present a 72‐year‐old nonsyndromic Japanese man with moderate‐sized aortic annulus ectasia (AAE) with moderate aortic regurgitation and ascending to distal arch aortic dilatation (maximum diameter: 46 mm). He had been treated for hypertension and dyslipidemia for 7 years, and his eldest son had AAE at 33 years old and type A aortic dissection at 43 years old. Surgical repair was considered a treatment option because the patient potentially had a nonsyndromic hereditary aortic disease, and genetic panel testing for TAAD identified a pathogenic missense variant in TGFBR1 (c.934G > A, p.[Gly312Ser]), previously reported in patients with LDS type 1. He was diagnosed with nonsyndromic TGFBR1‐related aortopathy and underwent prophylactic surgery using a modified Bentall operation and total arch replacement with open stent graft implantation. Genetic testing was useful in guiding the treatment strategy, but further analysis is warranted to establish the clinical value in the treatment plan for patients with elderly‐onset nonsyndromic TAAD. [ABSTRACT FROM AUTHOR]

Young seedlings use nutrients stored in the seeds to grow and acquire photosynthetic potential. This process, called seedling establishment, involves a developmental phase transition from heterotrophic to autotrophic growth. Some membrane-trafficking mutants of Arabidopsis (Arabidopsis thaliana), such as the katamari2 (kam2) mutant, exhibit growth arrest during seedling development, with a portion of individuals failing to develop true leaves on sucrose-free solid medium. However, the reason for this seedling arrest is unclear. In this study, we show that seedling arrest is a temporal growth arrest response that occurs not only in kam2 but also in wild-type (WT) Arabidopsis; however, the threshold for this response is lower in kam2 than in the WT. A subset of the arrested kam2 seedlings resumed growth after transfer to fresh sucrose-free medium. Growth arrest in kam2 on sucrose-free medium was restored by increasing the gel concentration of the medium or covering the surface of the medium with a perforated plastic sheet. WT Arabidopsis seedlings were also arrested when the gel concentration of sucrose-free medium was reduced. RNA sequencing revealed that transcriptomic changes associated with the rate of seedling establishment were observed as early as 4 d after sowing. Our results suggest that the growth arrest of both kam2 and WT seedlings is an adaptive stress response and is not simply caused by the lack of a carbon source in the medium. This study provides a new perspective on an environmental stress response under unfavorable conditions during the phase transition from heterotrophic to autotrophic growth in Arabidopsis. [ABSTRACT FROM AUTHOR]

Aim: We investigated the effects of pre‐transplantation renal dysfunction under left ventricular assisted device (LVAD) support on post‐transplantation cardiac function, and patient prognosis after heart transplantation (HTx). Method: All patients who were bridged by LVAD and underwent HTx at our hospital between 2007 and 2022 were included in this study. Patients were classified into two groups based on estimated glomerular filtration rate (eGFR) before HTx: renal dysfunction (RD) group (eGFR < 60 mL/min/1.73 m2) and non‐renal dysfunction (NRD) group. Result: A total of 132 patients were analyzed, of whom 48 were classified into the RD group and 84 into the NRD group (RD group, 47.9 ± 10.1 years; NRD group, 38.4 ± 11.9 years, p <.0001). Under LVAD support before HTx, the RD group tended to have a history of right ventricular failure (RD group, nine (19%); NRD group, seven (8%); p =.098). After HTx, the echocardiographic parameters did not differ between the two groups in the long term. Furthermore, more concise hemodynamic parameters, exemplified by right heart catheterization, were not significantly different between the two groups. Regarding graft rejection, no significant differences were found in acute cellular rejection and cardiac allograft vasculopathy following HTx. In contrast, patients with RD before HTx had significantly increased mortality in the chronic phase after HTx and initiation of maintenance dialysis, without any overt changes in cardiac function. Conclusion: Pre‐transplantation renal dysfunction under LVAD support significantly affected clinical course after HTx without any overt changes in graft cardiac function. [ABSTRACT FROM AUTHOR]

Objective: Loeys–Dietz syndrome (LDS) is a heritable disorder of connective tissue closely related to Marfan syndrome (MFS). LDS is caused by loss‐of‐function variants of genes that encode components of transforming growth factor‐β (TGF‐β) signaling; nevertheless, LDS type 1/2 caused by TGFBR1/2 pathogenic variants is frequently found to have paradoxical increases in TGF‐β signaling in the aneurysmal aortic wall. Here, we present a Japanese LDS family having a novel SMAD3 variant. Methods: The proband was tested via clinical, genetic, and histological analyses. In vitro analysis was performed for pathogenic evaluation. Results: The novel heterozygous missense variant of SMAD3 [c.1262G>A, p.(Cys421Tyr)], located just upstream of the C‐terminal Ser423‐X‐Ser425 phosphorylation motif, was found in this instance of LDS type 3. This variant led to reduced phospho‐SMAD3 (Ser423/Ser425) levels and transcription activity in vitro; however, a paradoxical upregulation of TGF‐β signaling was evident in the aortic wall. Conclusions: Our results revealed the presence of TGF‐β paradox in this case with the novel loss‐of‐function SMAD3 variant. The precise mechanism underlying the paradox is unknown, but further research is warranted to clarify the influence of the SMAD3 variant type and location on the LDS3 phenotype as well as the molecular mechanism leading to LDS3 aortopathy. [ABSTRACT FROM AUTHOR]

Hydathodes are typically found at leaf teeth in vascular plants and are involved in water release to the outside. Although morphological and physiological analysis of hydathodes has been performed in various plants, little is known about the genes involved in hydathode function. In this study, we performed fluorescent protein-based imaging and tissue-specific RNA-seq analysis in Arabidopsis hydathodes. We used the enhancer trap line E325, which has been reported to express green fluorescent protein (GFP) at its hydathodes. We found that E325-GFP was expressed in small cells found inside the hydathodes (named E cells) that were distributed between the water pores and xylem ends. No fluorescence of the phloem markers pSUC2:GFP and pSEOR1:SEOR1-YFP was observed in the hydathodes. These observations indicate that Arabidopsis hydathodes are composed of three major components: water pores, xylem ends, and E cells. In addition, we performed transcriptome analysis of the hydathode using the E325-GFP line. Microsamples were collected from GFP-positive or -negative regions of E325 leaf margins with a needle-based device (~130 µm in diameter). RNA-seq was performed with each single microsample using a high-throughput library preparation method called Lasy-Seq. We identified 72 differentially expressed genes. Among them, 68 genes showed significantly higher and four genes showed significantly lower expression in the hydathode. Our results provide new insights into the molecular basis for hydathode physiology and development. [ABSTRACT FROM AUTHOR]