Hormad1 mutation disrupts synaptonemal complex formation, recombination, and chromosome segregation in mammalian meiosis

Meiosis is unique to germ cells and essential for reproduction. During the first meiotic division, homologous chromosomes pair, recombine, and form chiasmata. The homologues connect via axial elements and numerous transverse filaments to form the synaptonemal complex. The synaptonemal complex is a critical component for chromosome pairing, segregation, and recombination. We previously identified a novel germ cell-specific HORMA domain encoding gene, Hormad1, a member of the synaptonemal complex and a mammalian counterpart to the yeast meiotic HORMA domain protein Hop1. Hormad1 is essential for mammalian gametogenesis as knockout male and female mice are infertile. Hormad1 deficient (Hormad1-/-) testes exhibit meiotic arrest in the early pachytene stage, and synaptonemal complexes cannot be visualized by electron microscopy. Hormad1 deficiency does not affect localization of other synaptonemal complex proteins, SYCP2 and SYCP3, but disrupts homologous chromosome pairing. Double stranded break formation and early recombination events are disrupted in Hormad1-/- testes and ovaries as shown by the drastic decrease in the γH2AX, DMC1, RAD51, and RPA foci. HORMAD1 co-localizes with cH2AX to the sex body during pachytene. BRCA1, ATR, and γH2AX co-localize to the sex body and participate in meiotic sex chromosome inactivation and transcriptional silencing. Hormad1 deficiency abolishes γH2AX, ATR, and BRCA1 localization to the sex chromosomes and causes transcriptional de-repression on the X chromosome. Unlike testes, Hormad1-/- ovaries have seemingly normal ovarian folliculogenesis after puberty. However, embryos generated from Hormad1-/- oocytes are hyper- and hypodiploid at the 2 cell and 8 cell stage, and they arrest at the blastocyst stage. HORMAD1 is therefore a critical component of the synaptonemal complex that affects synapsis, recombination, and meiotic sex chromosome inactivation and transcriptional silencing. © 2010 Shin et al

Elevated blood pressure aggravates intracerebral hemorrhage-induced brain injury

Elevated blood pressure (BP) is commonly seen in patients with intracerebral hemorrhage (ICH), and is independently associated with poor functional outcomes. Little is known about how elevated BP influences ICH-related brain injury. In the present study, we investigated the physiological and brain histological changes, as well as functional recovery following ICH in renovascular hypertensive rats. Renovascular hypertension (RVHT) was achieved by applying a silver clip onto the left renal artery of adult Sprague-Dawley rats. ICH was induced by an intrastriatal injection of bacterial collagenase IV about 5-6 weeks after left renal artery clipping or the sham operation. Following induction of ICH, both the normotensive and RVHT rats demonstrated an ultra-acute elevation in BP. Elevated BP increased hematoma volume, brain swelling, and apoptosis in the perihematomal areas. Brain degeneration, including local atrophy and lateral ventricle enlargement, was greater in the RVHT rats. In addition, many proliferating cells were seen over the ipsilateral striatum in the RVHT rats after ICH. The modified limb placing tests were done weekly for 3 weeks. In line with the histological damage, elevated BP worsened neurological deficits. These results suggest that ICH in the hypertensive rats mimics the clinical scenario of hypertensive ICH and may provide a platform to study the mechanisms of ICH-induced brain injury and potential therapies for ICH. © 2011, Mary Ann Liebert, Inc.published_or_final_versio

Orbital and Spin Parameter Variations of Partial Eclipsing Low Mass X-ray Binary X 1822-371

We report our measurements for orbital and spin parameters of X 1822-371 using its X-ray partial eclipsing profile and pulsar timing from data collected by the Rossi X-ray Timing Explorer (RXTE). Four more X-ray eclipse times obtained by the RXTE 2011 observations were combined with historical records to trace evolution of orbital period. We found that a cubic ephemeris likely better describes evolution of the X-ray eclipse times during a time span of about 34 years with a marginal second order derivative of $ddot{P}_{orb}=(-1.05 pm 0.59) imes 10^{-19}$ s$^{-1}$. Using the pulse arrival time delay technique, the orbital and spin parameters were obtained from RXTE observations from 1998 to 2011. The detected pulse periods show that the neutron star in X 1822-371 is continuously spun-up with a rate of $dot{P}_{s}=(-2.6288 pm 0.0095) imes 10^{-12}$ s s$^{-1}$. Evolution of the epoch of the mean longitude $l=pi /2$ (i.e. $T_{pi / 2}$) gives an orbital period derivative value consistent with that obtained from the quadratic ephemeris evaluated by the X-ray eclipse but the detected $T_{pi / 2}$ values are significantly and systematically earlier than the corresponding expected X-ray eclipse times by $90 pm 11$ s. This deviation is probably caused by asymmetric X-ray emissions. We also attempted to constrain the mass and radius of the neutron star using the spin period change rate and concluded that the intrinsic luminosity of X 1822-371 is likely more than $10^{38}$ ergs s$^{-1}$.postprin

QTL analysis of production traits on SSC3 in a Large White×Meishan pig resource family

In order to locate the genetic regions that are responsible for economically important traits, a resource population was established by crossing Large White boars and Meishan sows. Phenotypic data of a total of 287 F2 offspring were collected from 1998 to 2000 and QTL analysis conducted using nine microsatellites on Sus scrofa chromosome 3 (SSC3). Least square regression interval mapping revealed two significant QTL effects on dressing percentage and moisture in m. longissimus dorsi, respectively. They were located at 136 cM and 22 cM in the genetic linkage map, near the marker Sw349 and Swr1637, respectively. QTL for dressing percentage had an additive effect of -1.035 ± 0.296% and a dominance effect of 1.056 ± 0.481%, and the explained phenotypic variance was 15.9%. The additive and dominance effects of QTL for moisture in m. longissimus dorsi were -0.025 ± 0.076% and 0.365 ± 0.101%, respectively, indicating that this QTL seemed to be significantly dominant in action. The present study confirms previously identified QTL and provides an important step in the search for the actual major genes involved in the traits of economic interest. South African Journal of Animal Science Vol. 36(2) 2006: 122-12

Forehead EEG in Support of Future Feasible Personal Healthcare Solutions: Sleep Management, Headache Prevention, and Depression Treatment

© 2013 IEEE. There are current limitations in the recording technologies for measuring EEG activity in clinical and experimental applications. Acquisition systems involving wet electrodes are time-consuming and uncomfortable for the user. Furthermore, dehydration of the gel affects the quality of the acquired data and reliability of long-term monitoring. As a result, dry electrodes may be used to facilitate the transition from neuroscience research or clinical practice to real-life applications. EEG signals can be easily obtained using dry electrodes on the forehead, which provides extensive information concerning various cognitive dysfunctions and disorders. This paper presents the usefulness of the forehead EEG with advanced sensing technology and signal processing algorithms to support people with healthcare needs, such as monitoring sleep, predicting headaches, and treating depression. The proposed system for evaluating sleep quality is capable of identifying five sleep stages to track nightly sleep patterns. Additionally, people with episodic migraines can be notified of an imminent migraine headache hours in advance through monitoring forehead EEG dynamics. The depression treatment screening system can predict the efficacy of rapid antidepressant agents. It is evident that frontal EEG activity is critically involved in sleep management, headache prevention, and depression treatment. The use of dry electrodes on the forehead allows for easy and rapid monitoring on an everyday basis. The advances in EEG recording and analysis ensure a promising future in support of personal healthcare solutions

Determination and Distribution Study of Pogostone in Rat Tissues by Ultra-Fast Liquid Chromatography

Purpose: To develop and validate a rapid, sensitive and reliable ultra-fast liquid chromatography (UFLC) method with photodiode array (PDA) detection for the determination of pogostone (PO) in rat tissues using honokiol as internal standard (IS).Methods: Rats were randomly divided into two groups (intravenous administration group and oral administration group) and given of a single dose of 10 mg/kg PO by intravenous administration and oral administration, respectively. After intravenous injection, the rats were sacrificed at 15, 60 and 360 min, while rats, after oral administration, were euthanasized at 30, 90 and 360 min, respectively. For the analysis of the preparation, optimal chromatographic conditions were determined using Acquity UPLC BEH C18 column with acetonitrile-water containing 0.1 % formic acid (55:45, v/v) as the mobile phase, at a flow rate of 400 μL/min. UV detection wavelength was set at 310 nm with temperature maintained at 30 °C.Results: Good linear relationship of calibration curve (r > 0.9984) was achieved over the range of 0.1 - 40 μg/mL for all the tissue samples. The limit of quantification (LOQ) and limit of detection (LOD) were 0.1 and 0.05 μg/mL, respectively. This method proved to have good precision, accuracy, stability, extraction recovery and matrix effect for tissue distribution studies of PO in rats.Conclusion: The developed method is suitable for tissue distribution studies in rats following intravenous and oral administration of PO at a dose of 10 mg/kg.Keywords: Ultra-fast liquid chromatography, Tissue distribution, Pogostone, Honokiol, Rat

SWATH-MS Quantitative analysis of proteins in the rice inferior and superior spikelets during grain filling

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Correlation between promoter methylation of p14ARF, TMS1/ASC, and DAPK, and p53 mutation with prognosis in cholangiocarcinoma

<p>Abstract</p> <p>Background</p> <p>To study the methylation status of genes that play a role in the p53-Bax mitochondrial apoptosis pathway and its clinical significance in cholangiocarcinoma.</p> <p>Patients and Methods</p> <p>Out of 36 cases cholangiocarcinoma patients from April 2000 to May 2005 were collected.Promoter hypermethylation of <it>DAPK</it>, <it>p14^ARF</it>, and <it>ASC </it>were detected by methylation-specific PCR on cholangiocarcinoma and normal adjacent tissues samples. Mutation of the p53 gene was examined by automated sequencing. Correlation between methylation of these genes and/or <it>p53 </it>mutation status with clinical characteristics of patients was investigated by statistical analysis.</p> <p>Results</p> <p>We found 66.7% of 36 cholangiocarcinoma patients had methylation of at least one of the tumor suppressor genes analyzed. <it>p53 </it>gene mutation was found in 22 of 36 patients (61.1%). Combined <it>p53 </it>mutation and <it>DAPK, p14^ARF, and/or ASC </it>methylation was detected in 14 cases (38.9%). There were statistically significant differences in the extent of pathologic biology, differentiation, and invasion between patients with combined <it>p53 </it>mutation and <it>DAPK, p14^ARF, and/or ASC </it>methylation compared to those without (P < 0.05). The survival rate of patients with combined <it>DAPK, p14^ARF, and ASC </it>methylation and <it>p53 </it>mutation was poorer than other patients (<it>P </it>< 0.05).</p> <p>Conclusion</p> <p>Our study indicates that methylation of <it>DAPK, p14^ARF, and ASC </it>in cholangiocarcinoma is a common event. Furthermore, <it>p53 </it>mutation combined with <it>DAPK, p14^ARF, and/or ASC </it>methylation correlates with malignancy and poor prognosis.</p

ANALYSIS OF SPONTANEOUS IMBIBITION IN FRACTAL TREE-LIKE NETWORK SYSTEM

Spontaneous imbibition in porous media is common in nature, imbibition potential is very important for understanding the imbibition ability, or the ability to keep high imbibition rate for a long time. Structure parameters have influence on imbibition potential. This work investigates the process of spontaneous imbibition of liquid into a fractal tree-like network, taking fractal structure parameters into consideration. The analytical expression for dimensionless imbibition rate with this fractal tree-like network is derived. The influence of structure parameters on imbibition potential is discussed. It is found that optimal diameter ratio beta is important for networks to have imbibition potential. Moreover, with liquid imbibed in more sub-branches, some structures of parameter combinations will show the characteristic of imbibition potential gradually. Finally, a parameter plane is made to visualize the percentage of good parameter in all possible combinations and to evaluate the imbibition potential of a specific network system more directly. It is also helpful to design and to optimize a fractal network with good imbibition potential

Intervention effects of Ganoderma lucidum spores on epileptiform discharge hippocampal neurons and expression of Neurotrophin-4 and N-Cadherin

Epilepsy can cause cerebral transient dysfunctions. Ganoderma lucidum spores (GLS), a traditional Chinese medicinal herb, has shown some antiepileptic effects in our previous studies. This was the first study of the effects of GLS on cultured primary hippocampal neurons, treated with Mg2+ free medium. This in vitro model of epileptiform discharge hippocampal neurons allowed us to investigate the anti-epileptic effects and mechanism of GLS activity. Primary hippocampal neurons from <1 day old rats were cultured and their morphologies observed under fluorescence microscope. Neurons were confirmed by immunofluorescent staining of neuron specific enolase (NSE). Sterile method for GLS generation was investigated and serial dilutions of GLS were used to test the maximum non-toxic concentration of GLS on hippocampal neurons. The optimized concentration of GLS of 0.122 mg/ml was identified and used for subsequent analysis. Using the in vitro model, hippocampal neurons were divided into 4 groups for subsequent treatment i) control, ii) model (incubated with Mg2+ free medium for 3 hours), iii) GLS group I (incubated with Mg2+ free medium containing GLS for 3 hours and replaced with normal medium and incubated for 6 hours) and iv) GLS group II (neurons incubated with Mg2+ free medium for 3 hours then replaced with a normal medium containing GLS for 6 hours). Neurotrophin-4 and N-Cadherin protein expression were detected using Western blot. The results showed that the number of normal hippocampal neurons increased and the morphologies of hippocampal neurons were well preserved after GLS treatment. Furthermore, the expression of neurotrophin-4 was significantly increased while the expression of N-Cadherin was decreased in the GLS treated group compared with the model group. This data indicates that GLS may protect hippocampal neurons by promoting neurotrophin-4 expression and inhibiting N-Cadherin expression