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DExH-box helicases are involved in unwinding of RNA and DNA. Among the 16 DExH-box genes, monoallelic variants of DHX16, DHX30, DHX34, and DHX37 are known to be associated with neurodevelopmental disorders. In particular, DHX30 is well established as a causative gene for neurodevelopmental disorders. Germline variants of DHX9, the closest homolog of DHX30, have not been reported until now as being associated with congenital disorders in humans, except that one de novo heterozygous variant, p.(Arg1052Gln) of the gene was identified during comprehensive screening in a patient with autism; unfortunately, the phenotypic details of this individual are unknown. Herein, we report a patients with a heterozygous de novo missense variant, p.(Gly414Arg) of DHX9 who presented with a short stature, intellectual disability, and ventricular non-compaction cardiomyopathy. The variant was located in the glycine codon of the ATP-binding site, G-C-G-K-T. To assess the pathogenicity of these variants, we generated transgenic Drosophila lines expressing human wild-type and mutant DHX9 proteins: 1) the mutant proteins showed aberrant localization both in the nucleus and the cytoplasm; 2) ectopic expression of wild-type protein in the visual system led to the rough eye phenotype, whereas expression of the mutant proteins had minimal effect; 3) overexpression of the wild-type protein in the retina led to a reduction in axonal numbers, whereas expression of the mutant proteins had a less pronounced effect. Furthermore, in a gene-editing experiment of Dhx9 G416 to R416, corresponding to p.(Gly414Arg) in humans, heterozygous mice showed a reduced body size, reduced emotionality, and cardiac conduction abnormality. In conclusion, we established that heterozygosity for a loss-of-function variant of DHX9 can lead to a new neurodevelopmental disorder., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to disclose., (Copyright © 2023. Published by Elsevier Masson SAS.)

The activating transcription factor (ATF)2 family of transcription factors regulates a variety of metabolic processes, including adipogenesis and adaptive thermogenesis. ATF7 is a member of the ATF2 family, and mediates epigenetic changes induced by environmental stresses, such as social isolation and pathogen infection. However, the metabolic role of ATF7 remains unknown. The aim of the present study is to examine the role of ATF7 in metabolism using ATF7-dificeint mice. Atf7(-/-) mice exhibited lower body weight and resisted diet-induced obesity. Serum triglycerides, resistin, and adipose tissue mass were all significantly lower in ATF7-deficient mice. Fasting glucose levels and glucose tolerance were unaltered, but systemic insulin sensitivity was increased, by ablation of ATF7. Indirect calorimetry revealed that oxygen consumption by Atf7(-/-) mice was comparable to that of wild-type littermates on a standard chow diet, but increased energy expenditure was observed in Atf7(-/-) mice on a high-fat diet. Hence, ATF7 ablation may impair the development and function of adipose tissue and result in elevated energy expenditure in response to high-fat-feeding obesity and insulin resistance, indicating that ATF7 is a potential therapeutic target for diet-induced obesity and insulin resistance., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Faithful transcriptome regulation is important in development and also crucial for applications in reproductive and regenerative medicine. Intracytoplasmic sperm injection (ICSI), one of the human assisted reproductive technologies (ART), has long raised concerns about its influence on development. No clear consensus has been reached, however, in spite of many cohort studies carried out in the last two decades on the children conceived by ICSI and/or in vitro fertilization (IVF). In this study, the pre- and postnatal effects of ICSI were assessed using comprehensive transcriptome and phenotypic analyses in mice under strict conditions. Here we demonstrate that, in contrast to IVF, ICSI induces distinct long-lasting transcriptome change that remains at the neonatal stage. Importantly, no remarkable differences were observed in the ICSI adults in either the gene expression or phenotypic profiles, and there was no indication of transmission to the next generation via natural mating. Our results suggest there are no lifelong or transgenerational effects of ICSI, but the ICSI effects during neonatal period remain to be evaluated., (Copyright © 2011 Elsevier Inc. All rights reserved.)

We developed a simple and easy method for solution mixing based on the heat-induced regulation of capillary action in thermo-responsive polymer-coated microchannels. The channels having two T-junctions were fabricated on a glass plate by a sand-blast technique and then coated with a poly(N-isopropylacrylamide) film. The polymer-coating was performed by the modification with allyltrimethoxysilane and the subsequent radical polymerization of N-isopropylacrylamide and N,N'-methylenebisacrylamide. When the channel was warmed by a Peltier device, a capillarity-based solution flow completely stopped because of the water-repellency of channel surfaces. On the other hand, the cooling of the channels allowed the restart of the solution flow through hydrophilic channels. Solution mixing downstream a T-junction was readily conducted by a Peltier device that had placed at the junction. The technique was applied to the fluorometric analysis of polyamines in saliva. The saliva sample was mixed with nickel(II) chloride solution at the first junction to mask amino acids and then mixed with o-phthalaldehyde solution at the second junction to form the fluorometric derivatives of polyamines. Blue fluorescence was observed downstream the second junction. Linear correlation was obtained between the emission intensity and the spermine concentration in the range of 20-100 microM. No mechanical pump or valve was required for the fluid manipulation.

The pathways of thymic lymphomagenesis are classified as Rag-dependent or -independent according to their dependence on recombination-activating gene (Rag1/2) proteins. The role of the two-lymphoma pathways in oncogene rearrangements and the connection between lymphoma pathways and rearrangement mechanisms, however, remain obscure. We compared the incidence and latency of thymic lymphomas, and associated rearrangements of the representative oncogene Notch1 among Rag2(-/-), ataxia telangiectasia mutated (Atm)(-/-), and severe combined immune deficiency (scid) mice combined with Rag2 deficiency. Contrary to expectations, Rag2(-/-) mice were prone to thymic lymphoma development, suggesting the existence of a Rag2-independent lymphoma pathway in Rag2(-/-) mice. The lymphoma incidence in Rag2(-/-)Atm(-/-) mice was lower than that in Atm(-/-) mice, but higher than that in Rag2(-/-) mice, indicating that Atm(-/-) mice develop lymphomas through both pathways. Scid mice developed lymphomas with an incidence and latency similar to Rag2(-/-)scid mice, suggesting that Rag2-mediated V(D)J recombination-driven events are not necessarily required for lymphomagenesis in scid mice. Notch1 rearrangement mechanisms were classified as Rag2-dependent or Rag2-independent based on the presence of recombination signal-like sequences at rearranged sites. In Rag2(-/-) lymphomas, Notch1 must be rearranged independently of Rag2 function, implying that Rag2(-/-) mice are susceptible to lymphomagenesis due to the presence of other rearrangement mechanisms. The results in Atm(-/-) mice suggest that Notch1 was rearranged through both lymphoma pathways. In scid mice, the frequency of Rag2-mediated rearrangements was relatively low compared with that in wild-type mice, suggesting that the Rag2-independent lymphoma pathway prevails in the development of thymic lymphomas in scid mice. Thus, two rearrangement mechanisms underlie the lymphoma pathways and constitute the mechanistic bases for lymphomagenesis, thereby providing the molecular criteria for distinguishing between Rag2-dependent and Rag2-independent lymphoma pathways.

Background: The modified Harada-Ito procedure has been reported to be an effective treatment for correction of cyclotorsion in bilateral superior oblique palsy. However, there are no reports regarding its use in intraoperative adjustable suture surgery., Methods: The authors performed a retrospective study of 12 patients with traumatic bilateral superior oblique palsy who were classified as having either symmetric or asymmetric palsy according to the symmetry of the alternate hyperdeviation on side gazes. Cyclotorsion and vertical and horizontal deviation in the nine diagnostic positions were measured preoperatively and postoperatively., Results: Of the 12 patients, 6 were determined to have symmetric palsy and 6 asymmetric palsy. Intraoperative adjustable suture surgery with the modified Harada-Ito procedure was performed bilaterally in the six patients with symmetric palsy and unilaterally in those with asymmetric palsy. The median measured value of extorsion in the primary position was reduced from 14.5 degrees to 2.5 degrees in patients with symmetric palsy and from 9.5 degrees to 2.0 degrees in those with asymmetric palsy. In downgaze, some degree of residual extorsion remained, and there was no significant change in esodeviation after surgery. In five patients with symmetric palsy and in all of those with asymmetric palsy, normal single binocular vision in the primary position but did not that in downgaze was restored after surgery., Conclusion: Intraoperative adjustable suture surgery is an effective treatment in correcting torsion, but may not be as effective for esodeviation in downgaze.

Cardiac metastases have been reported increasingly partly because of the longevity of cancer patients, but its antemortem diagnosis is frequently missed. This is due to the nonspecific clinical manifestations or relative lack of characteristic signs which are masked by the underlying disease. This is a report of a 42-year-old man diagnosed as having a metastatic cardiac tumor by echocardiography, six months after operation for squamous cell carcinoma of the gall bladder. Echocardiography revealed abnormal structures in the regions of the posterior and lateral walls of the left ventricle and interventricular septum, suggesting metastatic tumors. The cytological findings of a fine-needle aspiration biopsy specimen were squamous cell carcinoma. The patient died of cardiac failure eight months after the echocardiographic diagnosis. At autopsy, the abnormal structures in the heart were identified as cardiac metastatic tumors from gall bladder cancer. Reports of cardiac metastasis of gall bladder cancer is very rare (0-3%). The myocardial metastasis may have a more serious prognostic importance than the primary neoplasm itself; thus, its definite diagnosis is mandatory.