Genetic insights on sleep schedules: this time, it's PERsonal.

The study of circadian rhythms is emerging as a fruitful opportunity for understanding cellular mechanisms that govern human physiology and behavior, fueled by evidence directly linking sleep disorders to genetic mutations affecting circadian molecular pathways. Familial advanced sleep-phase disorder (FASPD) is the first recognized Mendelian circadian rhythm trait, and affected individuals exhibit exceptionally early sleep-wake onset due to altered post-translational regulation of period homolog 2 (PER2). Behavioral and cellular circadian rhythms are analogously affected because the circadian period length of behavior is reduced in the absence of environmental time cues, and cycle duration of the molecular clock is likewise shortened. In light of these findings, we review the PER2 dynamics in the context of circadian regulation to reveal the mechanism of sleep-schedule modulation. Understanding PER2 regulation and functionality may shed new light on how our genetic composition can influence our sleep-wake behaviors

Sick and tired: how molecular regulators of human sleep schedules and duration impact immune function.

Why do we need to sleep? What regulates when we sleep? And what dictates the number of hours we require? These are often viewed as three separate biological questions. Here, we propose they share molecular etiologies, whereby regulators of sleep schedules and sleep duration also govern the physiological purposes of sleep. To support our hypothesis, we review Mendelian human genetic variants sufficient to advance sleep-wake onset (PER2) and shorten sleep length (DEC2), and evaluate their emerging roles in immune responses that may rely on a sound night of slumber

Aldose reductase deficiency protects the retinal neurons in a mouse model of retinopathy of prematurity

Poster Presentation: P64PURPOSE: Retinopathy of prematurity (ROP) is a common retinal disease occurred in premature babies. It is found to be related to oxidative stress while dysfunction of the neural retina has also been documented. We previously showed that genetic deletion or pharmacological inhibition of aldose reductase (AR), a rate- limiting enzyme in the polyol pathway, prevented ischemia-induced retinal ganglion cell (RGC) loss and oxidative stress. Here, we assessed the effects of AR deletion on retinal neurons using a mouse model of ROP. METHODS: Seven-day-old mouse pups were exposed to 75% oxygen for five days and returned to room air. The pathological neuronal changes were examined and compared between wild-type (WT) and AR-deficient retinae on P14 and P17 (P, postnatal). Retinal thickness was measured and immunohistochemistry for calbindin, calretinin, PKCα, Tuj1, glial fibrillary acidic protein (GFAP), nitrotyrosine (NT), as well as poly(ADP-ribose) (PAR) was performed. RESULTS: After hyperoxia exposure, significantly reduced inner nuclear layer (INL) and inner plexiform layer (IPL) thickness were found in both genotypes. The intensity of calbindin staining for horizontal cells in INL was reduced in the WT retinae but not in AR-deficient retinae. In addition, significant reduction was found in calretinin-positive amacrine cell bodies in central INL especially in WT retinae. Serious distortion was also observed in the three calretinin-positive strata along IPL in the WT retinae but not AR-deficient retinae on P17. Moreover, increased GFAP intensity across IPL indicating Müller cell processes was observed in AR-deficient retinae on P14 and in WT retinae on P17. Furthermore, increased NT immunoreactivity in INL and nuclear or para-nuclear PAR staining along GCL were observed in WT retina while these changes were not apparent in AR-deficient retina. CONCLUSION: Our observations demonstrated morphological changes of retinal neurons in the mouse model of ROP and indicated that AR deficiency showed neuronal protection in the retina, possibly through modulating glial responses and reducing oxidative stress.postprin

Primary hyperaldosteronism among Chinese hypertensive patients: how are we doing in a local district in Hong Kong

OBJECTIVES: To estimate the point prevalence of primary hyperaldosteronism in a government out-patient setting and to compare associated patient characteristics with those having essential hypertension. DESIGN: Case series with external comparison. SETTING: A single public hospital (Caritas Medical Centre) and all five associated general out-patient clinics in Sham Shui Po district in Hong Kong. PATIENTS: All patients with confirmed primary hyperaldosteronism and randomly selected patients with essential hypertension from a medical specialist clinic and general out-patient clinics, retrieved from a computer database for the period January 2007 to December 2008. MAIN OUTCOME MEASURES: Estimated point prevalence of primary hyperaldosteronism among hypertensive patients treated in the public sector of Sham Shui Po district. Patient age when hypertension was diagnosed, number of antihypertensive drugs used for treatment, and the presence of target organ damage in the patients with primary hyperaldosteronism and those with essential hypertension were compared. RESULTS: Among the 46 012 patients receiving antihypertensive treatment, 49 were confirmed to have primary hyperaldosteronism. The estimated point prevalence of primary hyperaldosteronism among these hypertensive patients was 0.106% only, which was far smaller than figures from other countries. When compared with the 147 patients with essential hypertension by multivariate analysis, those with primary hyperaldosteronism were: (1) associated with longer durations of hypertension (odds ratio=1.14; 95% confidence interval, 1.06-1.24) despite being younger at the time of study, (2) likely to be taking three or more antihypertensive drugs (odds ratio=2.51; 95% confidence interval, 1.59-3.95), and (3) more likely to have left ventricular hypertrophy (odds ratio=5.01; 95% confidence interval, 1.83-13.69). All primary hyperaldosteronism patients studied presented with hypokalaemia. The need for antihypertensive drugs was markedly reduced after adrenalectomy for adrenal adenoma. CONCLUSIONS: Primary hyperaldosteronism, which is potentially a surgically curable cause of hypertension, appeared to be underdiagnosed in our locality. Screening by aldosterone-renin ratio of high-risk individuals may help improve patient outcomes.published_or_final_versio

The space group classification of topological band insulators

Topological band insulators (TBIs) are bulk insulating materials which feature topologically protected metallic states on their boundary. The existing classification departs from time-reversal symmetry, but the role of the crystal lattice symmetries in the physics of these topological states remained elusive. Here we provide the classification of TBIs protected not only by time-reversal, but also by crystalline symmetries. We find three broad classes of topological states: (a) Gamma-states robust against general time-reversal invariant perturbations; (b) Translationally-active states protected from elastic scattering, but susceptible to topological crystalline disorder; (c) Valley topological insulators sensitive to the effects of non-topological and crystalline disorder. These three classes give rise to 18 different two-dimensional, and, at least 70 three-dimensional TBIs, opening up a route for the systematic search for new types of TBIs.Comment: Accepted in Nature Physic

The Effectiveness and Sustainability of a Universal School-Based Programme for Preventing Depression in Chinese Adolescents: A Follow-Up Study Using Quasi-Experimental Design

published_or_final_versio

Anti-inflammatory effects of lutein in retinal ischemic injury: in vivo and in vitro studies

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Strain-induced partially flat band, helical snake states, and interface superconductivity in topological crystalline insulators

Topological crystalline insulators in IV-VI compounds host novel topological surface states consisting of multi-valley massless Dirac fermions at low energy. Here we show that strain generically acts as an effective gauge field on these Dirac fermions and creates pseudo-Landau orbitals without breaking time-reversal symmetry. We predict the realization of this phenomenon in IV-VI semiconductor heterostructures, due to a naturally occurring misfit dislocation array at the interface that produces a periodically varying strain field. Remarkably, the zero-energy Landau orbitals form a flat band in the vicinity of the Dirac point, and coexist with a network of snake states at higher energy. We propose that the high density of states of this flat band gives rise to interface superconductivity observed in IV-VI semiconductor multilayers at unusually high temperatures, with non-BCS behavior. Our work demonstrates a new route to altering macroscopic electronic properties to achieve a partially flat band, and paves the way for realizing novel correlated states of matter.Comment: Accepted by Nature Physic

Nicotinic acetylcholine receptor expression in human airway correlates with lung function

Nicotine and its derivatives, by binding to nicotinic acetylcholine receptors (nAChRs) on bronchial epithelial cells, can regulate cellular signaling and inflammatory processes. Delineation of nAChR subtypes and their responses to nicotine stimulation in bronchial epithelium may provide information for therapeutic targeting in smoking-related inflammation in the airway. Expression of nAChR subunit genes in 60 bronchial epithelial biopsies and immunohistochemical staining for the subcellular locations of nAChR subunit expression were evaluated. Seven human bronchial epithelial cell lines (HBECs) were exposed to nicotine in vitro for their response in nAChR subunit gene expression to nicotine exposure and removal. The relative normalized amount of expression of nAChR α4, α5, and α7 and immunohistochemical staining intensity of nAChR α4, α5, and β3 expression showed significant correlation with lung function parameters. Nicotine stimulation in HBECs resulted in transient increase in the levels of nAChR α5 and α6 but more sustained increase in nAChR α7 expression. nAChR expression in bronchial epithelium was found to correlate with lung function. Nicotine exposure in HBECs resulted in both short and longer term responses in nAChR subunit gene expression. These results gave insight into the potential of targeting nAChRs for therapy in smoking-related inflammation in the airway.postprin

A topological Dirac insulator in a quantum spin Hall phase : Experimental observation of first strong topological insulator

When electrons are subject to a large external magnetic field, the conventional charge quantum Hall effect \cite{Klitzing,Tsui} dictates that an electronic excitation gap is generated in the sample bulk, but metallic conduction is permitted at the boundary. Recent theoretical models suggest that certain bulk insulators with large spin-orbit interactions may also naturally support conducting topological boundary states in the extreme quantum limit, which opens up the possibility for studying unusual quantum Hall-like phenomena in zero external magnetic field. Bulk Bi$_{1-x}$Sb$_x$ single crystals are expected to be prime candidates for one such unusual Hall phase of matter known as the topological insulator. The hallmark of a topological insulator is the existence of metallic surface states that are higher dimensional analogues of the edge states that characterize a spin Hall insulator. In addition to its interesting boundary states, the bulk of Bi$_{1-x}$Sb$_x$ is predicted to exhibit three-dimensional Dirac particles, another topic of heightened current interest. Here, using incident-photon-energy-modulated (IPEM-ARPES), we report the first direct observation of massive Dirac particles in the bulk of Bi$_{0.9}$Sb$_{0.1}$, locate the Kramers' points at the sample's boundary and provide a comprehensive mapping of the topological Dirac insulator's gapless surface modes. These findings taken together suggest that the observed surface state on the boundary of the bulk insulator is a realization of the much sought exotic "topological metal". They also suggest that this material has potential application in developing next-generation quantum computing devices.Comment: 16 pages, 3 Figures. Submitted to NATURE on 25th November(2007