The first Japanese familial sotos syndrome with a novel mutation of the NSD1 gene

Sotos syndrome is caused by the haploinsufficiency of the NSD1 gene located in5q35. More than 70% of the Japanese cases carry microdeletions encompassing ofthis gene, while point mutations are common in Caucasians. Only 15 familial cases ofSotos syndrome have been reported and all cases shown to have not microdeletions butpoint mutations. We identified the first Japanese familial case (mother and 3children). They carry the same mutation at splice donor site of intron 13(IVS13+1G>A), which results in the in-frame skipping of exon 13. This is also the firstfamilial case caused by the mutation of the splice donor site. Each member of thisfamily showed variable phenotypes and mental development. The present report willcontribute to further understanding of genotype-phenotype correlation in Sotossyndrome

Possible Realization of Topological Crystalline Superconductivity with Time-Reversal Symmetry in UTe2

The recent measurement of the de Haas-van Alphen effect in the spin-triplet superconductor UTe2 [D. Aoki et al., J. Phys. Soc. Jpn. 91, 083704 (2022)] supports cylindrical electron and hole Fermi surfaces, which implies that UTe2 is trivial as a 3D time-reversal-invariant topological superconductor. Inspired by this observation, we investigate the possible realization of a topological crystalline superconductor protected by the crystalline symmetry of UTe2. We examine Majorana surface states protected by mirror and two-fold rotational symmetries for all symmetry-allowed odd-parity pairing states with time-reversal symmetry and clarify the corresponding topological invariants. It is found that topological crystalline superconductivity can be realized for all irreducible representations of odd-parity pairing states of UTe2 even for cylindrical Fermi surfaces.Comment: 12 pages, 7 figure

Virulent Strain of Hepatitis E Virus Genotype 3, Japan

Virulence may be associated with mutation of the helicase domain (V239A), and source of the human infection may be swine

Effect of Nasal Continuous Positive Airway Pressure in Men on Global Left Ventricular Myocardial Performance in Patients With Obstructive Sleep Apnea Syndrome

The influence of obstructive sleep apnea syndrome (OSAS) on left ventricular function remains controversial. We examined the influence of OSAS on global left ventricular function using the myocardial performance index (Tei index) and plasma brain natriuretic peptide (BNP) level and investigated the effect of nasal continuous positive airway pressure (nCPAP) on these parameters. We obtained echocardiographic indexes including the Tei index and BNP concentrations from 27 patients with OSAS whose mean apnea--hypopnea index was 42.2 ± 21.5 events/hour and who were undergoing nCPAP and from 22 control subjects. We defined global left ventricular dysfunction (GLVD) as a Tei index ?0.50 and high BNP as ?20 pg/ml. Compared with controls, the Tei index of patients with OSAS was significantly increased (p <0.01) and prevalence of GLVD was high (19%, p <0.05). The correlation between the Tei index and apnea--hypopnea index was significant (r = 0.447, p <0.05). Although BNP levels were higher in patients with OSAS than in controls, the difference did not reach significance. BNP level was high in 37% of patients with OSAS and in only 9% of controls (p <0.05). The Tei index of patients with OSAS was significantly decreased after 1 month and 3 months of nCPAP (p <0.01), and prevalence of GLVD significantly decreased from 19% to 4% (p <0.05). In contrast, BNP significantly decreased at 3 months after nCPAP (p <0.05). In conclusion, patients with moderate to severe OSAS frequently have impaired global left ventricular myocardial performance, which can be reversed at the early stage after starting nCPAP.Without Table

B-MYB Is Essential for Normal Cell Cycle Progression and Chromosomal Stability of Embryonic Stem Cells

Background: The transcription factor B-Myb is present in all proliferating cells, and in mice engineered to remove this gene, embryos die in utero just after implantation due to inner cell mass defects. This lethal phenotype has generally been attributed to a proliferation defect in the cell cycle phase of G1. Methodology/Principal Findings: In the present study, we show that the major cell cycle defect in murine embryonic stem (mES) cells occurs in G2/M. Specifically, knockdown of B-Myb by short-hairpin RNAs results in delayed transit through G2/M, severe mitotic spindle and centrosome defects, and in polyploidy. Moreover, many euploid mES cells that are transiently deficient in B-Myb become aneuploid and can no longer be considered viable. Knockdown of B-Myb in mES cells also decreases Oct4 RNA and protein abundance, while over-expression of B-MYB modestly up-regulates pou5f1 gene expression. The coordinated changes in B-Myb and Oct4 expression are due, at least partly, to the ability of B-Myb to directly modulate pou5f1 gene promoter activity in vitro. Ultimately, the loss of B-Myb and associated loss of Oct4 lead to an increase in early markers of differentiation prior to the activation of caspase-mediated programmed cell death. Conclusions/Significance: Appropriate B-Myb expression is critical to the maintenance of chromosomally stable and pluripotent ES cells, but its absence promotes chromosomal instability that results in either aneuploidy or differentiation-associated cell death

Dissecting Oct3/4-Regulated Gene Networks in Embryonic Stem Cells by Expression Profiling

POU transcription factor Pou5f1 (Oct3/4) is required to maintain ES cells in an undifferentiated state. Here we show that global expression profiling of Oct3/4-manipulated ES cells delineates the downstream target genes of Oct3/4. Combined with data from genome-wide chromatin-immunoprecipitation (ChIP) assays, this analysis identifies not only primary downstream targets of Oct3/4, but also secondary or tertiary targets. Furthermore, the analysis also reveals that downstream target genes are regulated either positively or negatively by Oct3/4. Identification of a group of genes that show both activation and repression depending on Oct3/4 expression levels provides a possible mechanism for the requirement of appropriate Oct3/4 expression to maintain undifferentiated ES cells. As a proof-of-principle study, one of the downstream genes, Tcl1, has been analyzed in detail. We show that Oct3/4 binds to the promoter region of Tcl1 and activates its transcription. We also show that Tcl1 is involved in the regulation of proliferation, but not differentiation, in ES cells. These findings suggest that the global expression profiling of gene-manipulated ES cells can help to delineate the structure and dynamics of gene regulatory networks

Six RNA Viruses and Forty-One Hosts: Viral Small RNAs and Modulation of Small RNA Repertoires in Vertebrate and Invertebrate Systems

We have used multiplexed high-throughput sequencing to characterize changes in small RNA populations that occur during viral infection in animal cells. Small RNA-based mechanisms such as RNA interference (RNAi) have been shown in plant and invertebrate systems to play a key role in host responses to viral infection. Although homologs of the key RNAi effector pathways are present in mammalian cells, and can launch an RNAi-mediated degradation of experimentally targeted mRNAs, any role for such responses in mammalian host-virus interactions remains to be characterized. Six different viruses were examined in 41 experimentally susceptible and resistant host systems. We identified virus-derived small RNAs (vsRNAs) from all six viruses, with total abundance varying from “vanishingly rare” (less than 0.1% of cellular small RNA) to highly abundant (comparable to abundant micro-RNAs “miRNAs”). In addition to the appearance of vsRNAs during infection, we saw a number of specific changes in host miRNA profiles. For several infection models investigated in more detail, the RNAi and Interferon pathways modulated the abundance of vsRNAs. We also found evidence for populations of vsRNAs that exist as duplexed siRNAs with zero to three nucleotide 3′ overhangs. Using populations of cells carrying a Hepatitis C replicon, we observed strand-selective loading of siRNAs onto Argonaute complexes. These experiments define vsRNAs as one possible component of the interplay between animal viruses and their hosts