The treatment of patients suffering from benign paroxysmal positional vertigo with oscillation

Conference Theme: Challenges to specialists in the 21st centurypublished_or_final_versio

The roles of Irx3 and Irx5 in mammalian inner ear development

Iroquois genes encode a family of transcription factors containing TALE class homeodomain. They are regarded as prepatterning genes in Drosophila sensory organ development. There are six members (Irx1Irx6) of Iroquois genes in mouse and human. Irx3 and Irx5 are linked genes on mouse chromosome 8, which are involved in many mammalian developmental processes. However, the roles of Irx3 and Irx5 in mammalian hearing loss are poorly understood. To identify the function of these two genes in inner ear development, we have investigated two reporter knock‐in mouse mutants: Irx3lacZ, Irx5EGFP, and a double knock‐out mutant: Irx3/5‐/‐. Irx3 and Irx5 have overlapping expression domains in the developing inner ear. Physiological tests indicated that the Irx3lacZ and Irx5EGFP mutant mice displayed hearing defect, while Irx3/5‐/‐ mice were embryonic lethal. Although paint filling analysis showed the normal cochlea morphology of Irx3lacZ and Irx5EGFP mutant mice, ectopic inner hair cells have been discovered in the organ of Corti. Interestingly, the cochlear duct of Irx3/5‐/‐ mice was enlarged and shortened, and the basal part of the cochlea was fused with the saccule. There were also numerous vestibular‐like ectopic hair cells surrounded by ectopic Sox2‐positive cells in the greater epithelial ridge of cochlea. The organ of Corti was malformed with neither hair cell differentiation nor supporting cell differentiation at E16.5. In summary, our results indicate that Irx3 and Irx5 cooperatively pattern the boundary between the vestibule and the cochlea and they are important for the cochlear sensory neural cell specification.postprin

Ribose 2′-O-methylation provides a molecular signature for the distinction of self and non-self mRNA dependent on the RNA sensor Mda5

The 5'-cap-structures of higher eukaryote mRNAs are ribose 2'-O-methylated. Likewise, a number of viruses replicating in the cytoplasm of eukayotes have evolved 2'-O-methyltransferases to modify autonomously their mRNAs. However, a defined biological role of mRNA 2'-O-methylation remains elusive. Here we show that viral mRNA 2'-O-methylation is critically involved in subversion of type-I-interferon (IFN-I) induction. We demonstrate that human and murine coronavirus 2'-O-methyltransferase mutants induce increased IFN-I expression, and are highly IFN-I sensitive. Importantly, IFN-I induction by 2'-O-methyltransferase-deficient viruses is dependent on the cytoplasmic RNA sensor melanoma differentiation-associated gene 5 (MDA5). This link between MDA5-mediated sensing of viral RNA and mRNA 2'-O-methylation suggests that RNA modifications, such as 2'-O-methylation, provide a molecular signature for the discrimination of self and non-self mRNA

The influence of biological soil crusts on dew deposition in Gurbantunggut Desert, Northwestern China

Dew is an important source of moisture for plants, biological soil crusts, invertebrates and small vertebrates in desert environments. In this paper, measurements were taken to investigate the effects of three different types of biological soil crusts (cyanobacteria, lichen and moss) and bare sand on dew deposition in the Gurbantunggut Desert. Dew quantities were measured using micro-lysimeters with a diameter of 6 cm and a height of 3.5 cm. The results showed that the total amount of dew deposited increased with the development of soil crusts, from bare sand to cyanobacterial crust to lichen crust to moss crust. The average amount of dew deposited daily on the moss crust was the highest of all and it was significant higher than the other three soil surfaces (lichen crust, cyanobacterial crust and bare sand) (p < 0.05). During the period of the study, for each type of crust studied, the maximum amount of dew recorded was several times greater than the minimum. Moss crust was characterized by having the greatest amount of dew at dawn and also the maximum amount of dew deposited, whereas bare sand yielded the lowest amount of dew, with lichen crust and cyanobacterial crust exhibiting intermediate values. However, this was not the case for dew duration, as bare sand retained moisture for the longest period of time, followed by cyanobacterial crust, moss crust and finally lichen crust. Dew continued to condense even after sunrise. Furthermore, the differences in dew deposition may be partially attributed to an effect of the biological soil crusts on surface area. This study demonstrates the important effect of biological soil crusts upon dew deposition and may assist in evaluating the role of dew in and and semi-arid environments. (C) 2009 Elsevier B.V. All rights reserved

Poly(ADP-ribose) polymerase family member 14 (PARP14) is a novel effector of the JNK2-dependent pro-survival signal in multiple myeloma

Copyright @ 2013 Macmillan Publishers Limited. This is the author's accepted manuscript. The final published article is available from the link below.Regulation of cell survival is a key part of the pathogenesis of multiple myeloma (MM). Jun N-terminal kinase (JNK) signaling has been implicated in MM pathogenesis, but its function is unclear. To elucidate the role of JNK in MM, we evaluated the specific functions of the two major JNK proteins, JNK1 and JNK2. We show here that JNK2 is constitutively activated in a panel of MM cell lines and primary tumors. Using loss-of-function studies, we demonstrate that JNK2 is required for the survival of myeloma cells and constitutively suppresses JNK1-mediated apoptosis by affecting expression of poly(ADP-ribose) polymerase (PARP)14, a key regulator of B-cell survival. Strikingly, we found that PARP14 is highly expressed in myeloma plasma cells and associated with disease progression and poor survival. Overexpression of PARP14 completely rescued myeloma cells from apoptosis induced by JNK2 knockdown, indicating that PARP14 is critically involved in JNK2-dependent survival. Mechanistically, PARP14 was found to promote the survival of myeloma cells by binding and inhibiting JNK1. Moreover, inhibition of PARP14 enhances the sensitization of MM cells to anti-myeloma agents. Our findings reveal a novel regulatory pathway in myeloma cells through which JNK2 signals cell survival via PARP14, and identify PARP14 as a potential therapeutic target in myeloma.Kay Kendall Leukemia Fund, NIH, Cancer Research UK, Italian Association for Cancer Research and the Foundation for Liver Research

Absence of association between angiotensin converting enzyme polymorphism and development of adult respiratory distress syndrome in patients with severe acute respiratory syndrome: a case control study

BACKGROUND: It has been postulated that genetic predisposition may influence the susceptibility to SARS-coronavirus infection and disease outcomes. A recent study has suggested that the deletion allele (D allele) of the angiotensin converting enzyme (ACE) gene is associated with hypoxemia in SARS patients. Moreover, the ACE D allele has been shown to be more prevalent in patients suffering from adult respiratory distress syndrome (ARDS) in a previous study. Thus, we have investigated the association between ACE insertion/deletion (I/D) polymorphism and the progression to ARDS or requirement of intensive care in SARS patients. METHOD: One hundred and forty genetically unrelated Chinese SARS patients and 326 healthy volunteers were recruited. The ACE I/D genotypes were determined by polymerase chain reaction and agarose gel electrophoresis. RESULTS: There is no significant difference in the genotypic distributions and the allelic frequencies of the ACE I/D polymorphism between the SARS patients and the healthy control subjects. Moreover, there is also no evidence that ACE I/D polymorphism is associated with the progression to ARDS or the requirement of intensive care in the SARS patients. In multivariate logistic analysis, age is the only factor associated with the development of ARDS while age and male sex are independent factors associated with the requirement of intensive care. CONCLUSION: The ACE I/D polymorphism is not directly related to increased susceptibility to SARS-coronavirus infection and is not associated with poor outcomes after SARS-coronavirus infection