TALEN-mediated single-base-pair editing identification of an intergenic mutation upstream of BUB1B as causative of PCS (MVA) syndrome.

Cancer-prone syndrome of premature chromatid separation with mosaic variegated aneuploidy [PCS (MVA) syndrome] is a rare autosomal recessive disorder characterized by constitutional aneuploidy and a high risk of childhood cancer. We previously reported monoallelic mutations in the BUB1B gene (encoding BUBR1) in seven Japanese families with the syndrome. No second mutation was found in the opposite allele of any of the families studied, although a conserved BUB1B haplotype and a decreased transcript were identified.

Effect of botulinum toxin A on urothelial-release of ATP and expression of SNARE targets within the urothelium.

Aims: Botulinum neurotoxin serotype A (BoNT/A) has emerged as an effective treatment of urinary bladder overactivity. Intravesical lipotoxin (BoNT/A delivery using liposomes), which may target the urothelium, is effective in blocking acetic acid induced hyperactivity in animals. The objective of this study was to assess the possible site of toxin action within the urothelium.

Aminergic control of social status in crayfish agonistic encounters.

Using pairings of male crayfish Procambarus clarkii with a 3-7% difference in size, we confirmed that physically larger crayfish were more likely to win encounters (winning probability of over 80%). Despite a physical disadvantage, small winners of the first pairings were more likely to win their subsequent conflicts with larger naive animals (winning probability was about 70%). By contrast, the losers of the first pairings rarely won their subsequent conflicts with smaller naive animals (winning probability of 6%).

Haploinsufficiency of SAMD9L, an endosome fusion facilitator, causes myeloid malignancies in mice mimicking human diseases with monosomy 7.

Monosomy 7 and interstitial deletion of 7q (-7/7q-) are well-recognized nonrandom chromosomal abnormalities frequently found among patients with myelodysplastic syndromes (MDSs) and myeloid leukemias. We previously identified candidate myeloid tumor suppressor genes (SAMD9, SAMD9-like = SAMD9L, and Miki) in the 7q21.3 subband.

Identification of highly-disrupted tRNA genes in nuclear genome of the red alga, Cyanidioschyzon merolae 10D.

The limited locations of tRNA introns are crucial for eukaryal tRNA-splicing endonuclease recognition. However, our analysis of the nuclear genome of an early-diverged red alga, Cyanidioschyzon merolae, demonstrated the first evidence of nuclear-encoded tRNA genes that contain ectopic and/or multiple introns. Some genes exhibited both intronic and permuted structures in which the 3'-half of the tRNA coding sequence lies upstream of the 5'-half, and an intron is inserted into either half.

Alternative genetic code for amino acids and transfer RNA revisited.

The genetic code is highly conserved among all organisms and its evolution is thought to be strictly limited. However, an increasing number of studies have reported non-standard codes in prokaryotic and eukaryotic genomes. Most of these deviations from the standard code are attributable to tRNA changes relating to, for example, codon/anticodon base pairing and tRNA/aminoacyl-tRNA synthetase recognition.

Functionally distinct Gata3/Chd4 complexes coordinately establish T helper 2 (Th2) cell identity.

GATA binding protein 3 (Gata3) is a GATA family transcription factor that controls differentiation of naïve CD4 T cells into T helper 2 (Th2) cells. However, it is unknown how Gata3 simultaneously activates Th2-specific genes while repressing those of other Th lineages. Here we show that chromodomain helicase DNA-binding protein 4 (Chd4) forms a complex with Gata3 in Th2 cells that both activates Th2 cytokine transcription and represses the Th1 cytokine IFN-γ.

[Three patients with cervical disc herniation whose severe pain was relieved with oral mini-pulse therapy of betamethasone].

Three patients with severe neck and radicular pain due to cervical disc herniation was not relieved of pain by common drug medication such as NSAIDs and anticonvulsants. Patients underwent oral mini-pulse therapy of betamethasone as the initial dose of 8 mg x day(-1) in the form of 8 tablets of 0.5 mg in a single dose twice a day (after breakfast and after lunch).

Combination therapies with NS5A, NS3 and NS5B inhibitors on different genotypes of hepatitis C virus in human hepatocyte chimeric mice.

Objective: We recently demonstrated that combination treatment with NS3 protease and NS5B polymerase inhibitors succeeded in eradicating the virus in genotype 1b hepatitis C virus (HCV)-infected mice. In this study, we investigated the effect of combining an NS5A replication complex inhibitor (RCI) with either NS3 protease or NS5B inhibitors on elimination of HCV genotypes 1b, 2a and 2b.

Design: The effects of Bristol-Myers Squibb (BMS)-605339 (NS3 protease inhibitor; PI), BMS-788329 (NS5A RCI) and BMS-821095 (NS5B non-nucleoside analogue inhibitor) on HCV genotypes 1b and 2a were examined using subgenomic HCV replicon cells.

Comprehensive computational analysis of bacterial CRP/FNR superfamily and its target motifs reveals stepwise evolution of transcriptional networks.

The cAMP receptor protein (CRP)/fumarate and nitrate reduction regulatory protein (FNR)-type transcription factors (TFs) are members of a well-characterized global TF family in bacteria and have two conserved domains: the N-terminal ligand-binding domain for small molecules (e.g., cAMP, NO, or O(2)) and the C-terminal DNA-binding domain.

Identification of the integrin β3 L718P mutation in a pedigree with autosomal dominant thrombocytopenia with anisocytosis.

αIIbβ3 integrin mutations that result in the complete loss of expression of this molecule on the platelet surface cause Glanzmann thrombasthenia. This is usually autosomal recessive, while other mutations are known to cause dominantly inherited macrothrombocytopenia (although such cases are rare). Here, we report a 4-generation pedigree including 10 individuals affected by dominantly inherited thrombocytopenia with anisocytosis.

The postpartum depressive state in relation to perceived rearing: a prospective cohort study.

Background: The relationship between perceived rearing and the postpartum depressive state remains unclear. We aimed to examine whether perceived rearing is a risk factor for postpartum depression as measured by the Edinburgh Postnatal Depression Scale (EPDS), and whether the score of perceived rearing is affected by depressive mood (the state dependency of perceived rearing).

Methods: Pregnant women (n = 448, mean age 31.

The effects of vitamin A compounds on hyaluronic acid released from cultured rabbit corneal epithelial cells and keratocytes.

A role of vitamin A in the synthesis of hyaluronic acid by skin cells is well known. Hyaluronic acid is produced by corneal epithelial cells and keratocytes in the eye. We investigated whether rabbit corneal epithelial cells and keratocytes release hyaluronic acid after exposure to vitamin A compounds.

X-ray structure of the fourth type of archaeal tRNA splicing endonuclease: insights into the evolution of a novel three-unit composition and a unique loop involved in broad substrate specificity.

Cleavage of introns from precursor transfer RNAs (tRNAs) by tRNA splicing endonuclease (EndA) is essential for tRNA maturation in Archaea and Eukarya. In the past, archaeal EndAs were classified into three types (α'2, α4 and α2β2) according to subunit composition. Recently, we have identified a fourth type of archaeal EndA from an uncultivated archaeon Candidatus Micrarchaeum acidiphilum, referred to as ARMAN-2, which is deeply branched within Euryarchaea.

[Xenon light therapy].

The xenon light, generated by high-intensity electrical stimulation of xenon gas, is used to sterilize wounds, aid tissue repair, and relieve pain as a low-level light therapy. The light produced consists of non-coherent beams of multiple wavelengths in the ultraviolet to infrared spectrum. This broad-band light can be emitted in a continuous wave or pulsed mode, with the wave band chosen and the energy distribution controlled for the purpose.

A crucial role of bone morphogenetic protein signaling in the wound healing response in acute liver injury induced by carbon tetrachloride.

Background. Acute liver injury induced by administration of carbon tetrachloride (CCl(4)) has used a model of wound repair in the rat liver. Previously, we reported transient expression of bone morphogenetic protein (Bmp) 2 or Bmp4 at 6-24 h after CCl(4) treatment, suggesting a role of BMP signaling in the wound healing response in the injured liver.

Prospective study on the association between harm avoidance and postpartum depressive state in a maternal cohort of Japanese women.

Background: Recent studies have displayed increased interest in examining the relationship between personality traits and the onset, treatment response patterns, and relapse of depression. This study aimed to examine whether or not harm avoidance (HA) was a risk factor for postpartum depression measured by the Edinburgh Postnatal Depression Scale (EPDS) and the state dependency of HA.

Methods: Pregnant women (n=460; mean age 31.

Botulinum neurotoxin serotype A suppresses neurotransmitter release from afferent as well as efferent nerves in the urinary bladder.

Background: Botulinum neurotoxin A (BoNTA), which alleviates overactive bladder symptoms, is thought to act predominantly via the inhibition of transmitter release from parasympathetic nerves. However, actions at other sites such as afferent nerve terminals are possible.

Objective: To evaluate the effects of BoNTA on bladder afferent neuropeptide release and firing.

Genomic heterogeneity in a natural archaeal population suggests a model of tRNA gene disruption.

Understanding the mechanistic basis of the disruption of tRNA genes, as manifested in the intron-containing and split tRNAs found in Archaea, will provide considerable insight into the evolution of the tRNA molecule. However, the evolutionary processes underlying these disruptions have not yet been identified. Previously, a composite genome of the deep-branching archaeon Caldiarchaeum subterraneum was reconstructed from a community genomic library prepared from a C.

Modulation of spontaneous activity in the overactive bladder: the role of P2Y agonists.

Spinal cord transection (SCT) leads to an increase in spontaneous contractile activity in the isolated bladder that is reminiscent of an overactive bladder syndrome in patients with similar damage to the central nervous system. An increase in interstitial cell number in the suburothelial space between the urothelium and detrusor smooth muscle layer occurs in SCT bladders, and these cells elicit excitatory responses to purines and pyrimidines such as ATP, ADP, and UTP. We have investigated the hypothesis that these agents underlie the increase in spontaneous activity.

Systems Biology Reveals MicroRNA-Mediated Gene Regulation.

MicroRNAs (miRNAs) are members of the small non-coding RNAs, which are principally known for their functions as post-transcriptional regulators of target genes. Regulation by miRNAs is triggered by the translational repression or degradation of their complementary target messenger RNAs (mRNAs). The growing number of reported miRNAs and the estimate that hundreds or thousands of genes are regulated by them suggest a magnificent gene regulatory network in which these molecules are embedded.

Mechanisms of action of botulinum neurotoxins, β3-adrenergic receptor agonists, and PDE5 inhibitors in modulating detrusor function in overactive bladders: ICI-RS 2011.

Background: Botulinum neurotoxins type A (BoNT/A), β(3)-adrenergic receptor agonists, and phosphodiesterase type 5 (PDE5) inhibitors are promising agents that mitigate lower urinary tract symptoms by attenuating the sensory system. However, whether they act directly on afferent nerves or indirectly through the other cell types is unclear.

Methods: Spinal cord transected female mice were used as a model for neurogenic bladder overactivity.

Nematode-specific tRNAs that decode an alternative genetic code for leucine.

Class II transfer RNAs (tRNAs), including tRNA(Leu) and tRNA(Ser), have an additional stem and loop structure, the long variable arm (V-arm). Here, we describe Class II tRNAs with a unique anticodon corresponding to neither leucine nor serine. Because these tRNAs are specifically conserved among the nematodes, we have called them 'nematode-specific V-arm-containing tRNAs' (nev-tRNAs).

Facile synthesis and evaluation of C-functionalized benzyl-1-oxa-4,7,10-triazacyclododecane-N,N',N″-triacetic acid as chelating agent for ¹¹¹In-labeled polypeptides.

A 12-membered polyazamacrocycle, 1-oxa-4,7,10-triazacyclododecane-N,N',N″-triacetic acid (ODTA), has been reported to provide an indium chelate of net neutral charge with thermodynamic stability higher than 1,4,7,10-tetraazacyclododecane-N,N',N″,N‴-tetraacetic acid (DOTA). However, neither synthetic procedure for a C-functionalized ODTA (C-ODTA) nor its chelating ability with a trace amount of radioactive indium-111 ((111)In) has been elucidated. We herein present a facile synthetic procedure for C-ODTA, and estimated its ability as a chelating agent for radiolabeling peptides and proteins with (111)In.