A γA-Crystallin Mouse Mutant Secc with Small Eye, Cataract and Closed Eyelid

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Analysis of craniofacial defects in Six1/Eya1-associated Branchio-Oto-Renal Syndrome

Poster Session I - Morphogenesis: 205/B10117th ISDB 2013 cum 72nd Annual Meeting of the Society for Developmental Biology, 7th Latin American Society of Developmental Biology Meeting and 11th Congreso de la Sociedad Mexicana de Biologia del Desarrollo.Branchio-Oto-Renal (BOR) syndrome patients exhibit craniofacial and renal anomalies as well as deafness. BOR syndrome is caused by mutations in Six1 or Eya1, both of which regulate cell proliferation and differentiation. The molecular mechanism underlying the craniofacial and branchial arch (BA) defects in BOR syndrome is unclear. We have found that Hoxb3 is up-regulated in the second branchial arch (BA2) of Six1-/- mutants. Moreover, Hoxb3 over-expression in transgenic mice leads to BA abnormalities which are similar to the BA defects in Six1-/- or Eya1-/- mutants, suggesting a regulatory relationship among Six1, Eya1 and Hoxb3 genes. The aim of this study is to investigate the molecular mechanism underlying abnormal BA development in BOR syndrome using Six1 and Eya1 mutant mice. Two potential Six1 binding sites were identified on the Hoxb3 gene. In vitro and in vivo Chromatin IP assays showed that Six1 could directly bind to one of the sites specifically. Furthermore, using a chick in ovo luciferase assay we showed that Six1 could suppress gene expression through one of the specific binding sites. On the other hand, in Six1-/- mutants, we found that the Notch ligand Jag1 was up-regulated in BA2. Similarly, in Hoxb3 transgenic mice, ectopic expression of Jag1 could be also detected in BA2. To investigate the activation of Notch signaling pathway, we found that Notch intracellular domain (NICD), a direct indicator of Notch pathway activation, was up-regulated in BAs of Six1-/-; Eya1-/- double mutants. Our results indicate that Hoxb3 and Notch signaling pathway are involved in mediating the craniofacial defects of Six1/Eya1-associated Branchio-Oto-Renal Syndrome.postprin

Cyp26b1 mediates differential regulation of RA signaling in neural progenitor populations along the anteriorposterior axis of the adult spinal cord

Poster Session - Neural Regeneration: no. 64DMM 2011 entitled: Re-engineering Regenerative MedicineNeural stem cells from the adult subventricular zone (SVZ) are highly heterogeneous, with their position of origin being a key factor in determining the neuronal subtype they can give rise to. Whether this diversity extends to other regions in the adult CNS has not been demonstrated. In vitro studies with directed neuronal differentiation of ES cells suggest that subtype specification may be regulated by the positional identity present in the ES‐derived cell, since altering the positional identity leads to corresponding changes in motor neuron subtype. This limited plasticity suggests the position identity of the original stem cell source is a critical factor for the generation of the desired neuronal subtype. The adult spinal cord consists of endogenous stem/progenitor cells which are …postprin

Cyp26b1 mediates differential neurogenicity in axial-specific populations of adult spinal cord progenitor cells

Utilization of endogenous adult spinal cord progenitor cells (SCPCs) for neuronal regeneration is a promising strategy for spinal cord repair. To mobilize endogenous SCPCs for injury repair, it is necessary to understand their intrinsic properties and to identify signaling factors that can stimulate their neurogenic potential. In this study, we demonstrate that adult mouse SCPCs express distinct combinatorial Hox genes and exhibit axial-specific stem cell properties. Lumbar-derived neurospheres displayed higher primary sphere formation and greater neurogenicity compared with cervical- and thoracic-derived neurospheres. To further understand the mechanisms governing neuronal differentiation of SCPCs from specific axial regions, we examined the neurogenic responses of adult SCPCs to retinoic acid (RA), an essential factor for adult neurogenesis. Although RA is a potent inducer of neuronal differentiation, we found that RA enhanced the generation of neurons specifically in cervical- but not lumbar-derived cells. We further demonstrate that the differential RA response was mediated by the RA-degrading enzyme cytochrome P450 oxidase b1 Cyp26b1. Lumbar cells express high levels of Cyp26b1 and low levels of the RA-synthesizing enzyme retinaldehyde dehydrogenase Raldh2, resulting in limited activation of the RA signaling pathway in these cells. In contrast, low Cyp26b1 expression in cervical spinal cord progenitor cells allows RA signaling to be readily activated upon RA treatment. The intrinsic heterogeneity and signaling factor regulation among adult SCPCs suggest that different niche factor regimens are required for site-specific mobilization of endogenous SCPCs from distinct spatial regions of the spinal cord for injury repair.published_or_final_versio

Predictive factors for extracorporeal shockwave lithotripsy success in ureteric stones, does skin-stone distance and hounsfield unit matter?

OBJECTIVE: To evaluate the usefulness of measuring stone skin distance and stone attenuation values by non-contrast computed tomography for predicting treatment outcome of ureteric stones by extracorporeal shockwave lithotripsy (ESWL). PATIENT AND METHOD : Retrospective review of 66 patients who underwent ESWL for ureteric stones with pre-ESWL NCCT in 2010–2012. Subjects were stratified into 2 groups, successful ESWL and failed ESWL, with ESWL success defined as stone fragment less than 4 mm at 6 weeks after ESWL. Patient age, sex, stone size, stone location, laterality, shockwave energy, number of shockwave administered, Hounsfield unit (HU), skin to stone distance (SSD), presence of hydronephrosis, pre-ESWL JJ stent or PCN were studied as predictive factors. RESULTS : Patient demographics and stone characteristics were similar between the 2 groups. On univariate analysis, the mean stone size for successful ESWL was 7.9 mm compared with 10.2 mm in the failure group (P = 0.02). For the skin-stone distance, the mean distance for the successful group was 95 mm compared with 104 mm in the failure group (P = 0.04). Concerning the Hounsfield Unit, a mean of 1034 HU was found in the successful compared with 1129 HU in the failure group (P = 0.16) CONCLUSION : Skin to stone distance on non-contrast CT scan is a useful predictive factors for ESWL success for ureteric stones.postprin

Validation of the perceived stress scale (Pss-10) in medical and health sciences students in Hong Kong

INTRODUCTION: The demanding nature of medical and health sciences studies can cause stress among students in these disciplines affecting their wellbeing and academic performance. The Perceived Stress Scale (PSS-10) is a widely used measure of perceived stress among medical students and healthcare professionals that has not yet been validated among medical and health sciences students in Hong Kong. The aim of this study is to establish the construct validity and reliability of the PSS-10 in this context. METHODS: 267 final year medical and health sciences students were surveyed using the PSS-10. The data were analysed using exploratory factor analysis for construct validity and Cronbach’s alpha coefficient and corrected item-total correlations for reliability. RESULTS: Exploratory factor analysis revealed a two-factor structure for PSS-10, with Cronbach’s alpha of 0.865 and 0.796, indicating good internal consistency. Corrected item-total correlations showed satisfactory correlation ranged from 0.539 to 0.748 for all items and their respective subscale. Both tests supported PSS-10 as a two-factor scale. CONCLUSIONS: The PSS-10 is a valid measure for assessing perceived stress in Hong Kong medical and health sciences students

Cardiomyocyte Ca2+ handling and structure is regulated by degree and duration of mechanical load variation

Cardiac transverse (t)-tubules are altered during disease and may be regulated by stretch-sensitive molecules. The relationship between variations in the degree and duration of load and t-tubule structure remains unknown, as well as its implications for local Ca2+-induced Ca2+ release (CICR). Rat hearts were studied after 4 or 8 weeks of moderate mechanical unloading [using heterotopic abdominal heart–lung trans-plantation (HAHLT)] and 6 or 10 weeks of pressure overloading using thoracic aortic constriction. CICR, cell and t-tubule structure were assessed using confocal-microscopy, patch-clamping and scanning ion conductance microscopy. Moderate unloading was compared with severe unloading [using heart-only transplantation (HAHT)]. Mechanical unloading reduced cardiomyocyte volume in a time-dependent manner. Ca2+ release synchronicity was reduced at 8 weeks moderate unloading only. Ca2+ sparks increased in frequency and duration at 8 weeks of moderate unloading, which also induced t-tubule disorganization. Overloading increased cardiomyocyte volume and disrupted t-tubule mor-phology at 10 weeks but not 6 weeks. Moderate mechanical unloading for 4 weeks had milder effects compared with severe mechanical unloading (37 % reduction in cell volume at 4 weeks compared to 56 % reduction after severe mechanical unloading) and did not cause depres-sion and delay of the Ca2+ transient, increased Ca2+ spark frequency or impaired t-tubule and cell surface structure. These data suggest that variations in chronic mechanical load influence local CICR and t-tubule structure in a time- and degree-dependent manner, and that physiologi-cal states of increased and reduced cell size, without pathological changes are possible

Occult alpha globin gene mutations are the commonest causes of red cell microcytosis unexplained by phenotypic testing

HAA: Haematology Society of Australia and New Zealand, The Australian & New Zealand Society of Blood Transfusion and The Australasian Society of Thrombosis and HaemostasisAIM: Hypochromic microcytic anaemia is the hallmark phenotype of thalassaemia. Current phenotypic tests do not provide a diagnosis in a small proportion of patients with red cell microcytosis. We investigated the genetic basis of microcytosis in a cohort of such subjects. METHOD: We identified from a large cohort of 1684 unselected requests for thalassaemia testing 25 Chinese subjects who had unexplained microcytosis after phenotypic haemoglobin studies. Extensive genotypic analysis of the α and β globin gene cluster was performed in 20 of these subjects who had adequate DNA. Techniques employed included gap-polymerase chain reaction, amplification-refractory mutation system, Sanger sequencing and multiplex ligation-dependent …postprin

The relationship between renal stone excursion distance and body build during ESWL

香港泌尿外科學會Oral (Free Paper) Session IV - Andrology, Men’s Health and Stone Disease: OP.4-4AIM: To study the relationship between body build and renal stone excursion distance during ESWL. PATIENTS AND METHODS: 88 consecutive patients with different urinary stones underwent ESWL from Oct 2010 to Feb 2011. Patients with ureteric stone, incomplete data, double-J stent and PCN in-situ were excluded. Stone characteristics including burden, position and excursion at deep inspiration and ...published_or_final_versionThe 17th Annual Scientific Meeting of the Hong Kong Urological Association, Hong Kong, 6 November 2011. In Program Book, 2011, p. 5

RingCT 2.0: A Compact Accumulator-Based (Linkable Ring Signature) Protocol for Blockchain Cryptocurrency Monero

In this work, we initially study the necessary properties and security requirements of Ring Confidential Transaction (RingCT) protocol deployed in the popular anonymous cryptocurrency Monero. Firstly, we formalize the syntax of RingCT protocol and present several formal security definitions according to its application in Monero. Based on our observations on the underlying (linkable) ring signature and commitment schemes, we then put forward a new efficient RingCT protocol (RingCT 2.0), which is built upon the well-known Pedersen commitment, accumulator with one-way domain and signature of knowledge (which altogether perform the functions of a linkable ring signature). Besides, we show that it satisfies the security requirements if the underlying building blocks are secure in the random oracle model. In comparison with the original RingCT protocol, our RingCT 2.0 protocol presents a significant space saving, namely, the transaction size is independent of the number of groups of input accounts included in the generalized ring while the original RingCT suffers a linear growth with the number of groups, which would allow each block to process more transactions