A Series of N-terminal Epitope Tagged Hdh Knock-In Alleles Expressing Normal and Mutant Huntingtin: Their Application to Understanding the Effect of Increasing the Length of Normal Huntingtin’s Polyglutamine Stretch on CAG140 Mouse Model Pathogenesis

Background: Huntington’s disease (HD) is an autosomal dominant neurodegenerative disease that is caused by the expansion of a polyglutamine (polyQ) stretch within Huntingtin (htt), the protein product of the HD gene. Although studies in vitro have suggested that the mutant htt can act in a potentially dominant negative fashion by sequestering wild-type htt into insoluble protein aggregates, the role of the length of the normal htt polyQ stretch, and the adjacent proline-rich region (PRR) in modulating HD mouse model pathogenesis is currently unknown. Results: We describe the generation and characterization of a series of knock-in HD mouse models that express versions of the mouse HD gene (Hdh) encoding N-terminal hemaglutinin (HA) or 3xFlag epitope tagged full-length htt with different polyQ lengths (HA7Q-, 3xFlag7Q-, 3xFlag20Q-, and 3xFlag140Q-htt) and substitution of the adjacent mouse PRR with the human PRR (3xFlag20Q- and 3xFlag140Q-htt). Using co-immunoprecipitation and immunohistochemistry analyses, we detect no significant interaction between soluble full-length normal 7Q- htt and mutant (140Q) htt, but we do observe N-terminal fragments of epitope-tagged normal htt in mutant htt aggregates. When the sequences encoding normal mouse htt’s polyQ stretch and PRR are replaced with non-pathogenic human sequence in mice also expressing 140Q-htt, aggregation foci within the striatum, and the mean size of htt inclusions are increased, along with an increase in striatal lipofuscin and gliosis. Conclusion: In mice, soluble full-length normal and mutant htt are predominantly monomeric. In heterozygous knock-in HD mouse models, substituting the normal mouse polyQ and PRR with normal human sequence can exacerbate some neuropathological phenotypes

Sodomy of Adolescent Males Presented to Pediatric Psychiatric Outpatient Clinic: A Case Series

Traditional Arab culture hides male sexual abuse and considers it a shame. Instead of treating male victims of sexual assault, they are often stigmatized as homosexual individuals. Moreover, guardians of sexually abused boys are also negatively affected. They have to choose between reporting abuse to a legal authority with the risk of labeling their child or keeping a close eye on them to prevent further abuse. However, reporting abuse to healthcare authorities does take place. Disclosing sexual abuse in the privacy of a psychiatric clinic is often the only way for victims to be successfully treated for the psychological effects of such abuse

The signaling lipid sphingosine 1-phosphate regulates mechanical pain

Somatosensory neurons mediate responses to diverse mechanical stimuli, from innocuous touch to noxious pain. While recent studies have identified distinct populations of A mechanonociceptors (AMs) that are required for mechanical pain, the molecular underpinnings of mechanonociception remain unknown. Here, we show that the bioactive lipid sphingosine 1-phosphate (S1P) and S1P Receptor 3 (S1PR3) are critical regulators of acute mechanonociception. Genetic or pharmacological ablation of S1PR3, or blockade of S1P production, significantly impaired the behavioral response to noxious mechanical stimuli, with no effect on responses to innocuous touch or thermal stimuli. These effects are mediated by fast-conducting A mechanonociceptors, which displayed a significant decrease in mechanosensitivity in S1PR3 mutant mice. We show that S1PR3 signaling tunes mechanonociceptor excitability via modulation of KCNQ2/3 channels. Our findings define a new role for S1PR3 in regulating neuronal excitability and establish the importance of S1P/S1PR3 signaling in the setting of mechanical pain thresholds

LBIC ANALYSIS FOR GRAIN-BOUNDARY CHARACTERIZATION IN INHOMOGENEOUS MATERIALS

The interfacial recombination velocity S of Grain-Boundaries (G.B.'s) may be evaluated by means of LBIC scan line at wavelength λ ≥ 940 nm using a finite diameter light spot. ZOOK /1/ has proposed a method to determine S, based on the photocurrent attenuation within a G.B., assuming that the minority carrier diffusion length L in the grains is constant. This assumption is not experimentally verified and causes large errors in the S evaluation

Caracterisation, passivation et modelisation de l'influence de defauts cristallographiques sur les proprietes de jonctions NP

CNRS T Bordereau / INIST-CNRS - Institut de l'Information Scientifique et TechniqueSIGLEFRFranc

The legend of Cairo : kisah penguasa agung kota seribu menara

Berlatar Kairo awal abad ke-16, sejak masa akhir Dinasti Mamluk hingga Mesir jatuh di bawah kekuasaan Utsmani pada 1517, novel ini menceritakan kiprah seorang muhtasib Mesir terkemuka, Zayni Barakat bin Musa, yang juga menjabat gubernur Kairo. Di era Mamluk, seorang muhtasib tidak saja bertugas mengontrol harga dan kualitas barang di pasaran tetapi juga bertanggung jawab memonitor perilaku masyarakat agar sesuai dengan kaidah moral. Di tengah situasi politik dan keamaanan yang tak menentu, ia mengendalikan kota yang korup melalui jaringan rumit mata-mata dan para pelapor. Sebagai pemimpin yang saleh dan terpuji, jujur dan adil, bijaksana dan berintegritas, kuat dan tegas, serta disiplin dan efektif, ia dipuji dan dicintai banyak orang. Keberpihakannya pada rakyat ditunjukkan antara lain dengan sikap tidak pandang bulu terhadap si kaya dan si miskin atau si kuat dan si lemah, serta kesediaan berkomunikasi secara langsung dengan masyarakat lapisan bawah, sesuatu yang tidak pernah dilakukan muhtasib mana pun sebelumnya. Sejumlah narator, di antaranya seorang petualang dari Venesia dan beberapa narator Muslim, menuturkan kisah kebangkitan sang tokoh yang tegas, enigmatik, dan puritan ini. Dengan beberapa karakter yang diangkat dari tokoh nyata, termasuk Zayni Barakat sendiri, novel ini menjadi bacaan yang memancarkan informasi penting ihwal situasi sebenarnya Mesir kala itu. Inilah epos tentang sang tokoh sekaligus serpihan sejarah Kota Seribu Menara, Kairo

The Legend of Cairo Kisah Penguasa Agung Kota Seribu Manara

376 hlm.; 20 cm

Influence of dislocations on dark current of multicrystalline silicon N+^+ P junction

A detailed characterization of the dark current in large grained polycristalline silicon cells is given. This current is greatly influenced by the presence of dislocations. A new model for the shunt current transmitted by these defects is given. It is found that this current is proportional to $\exp(qV/2 kT)$. The comparison between the three essential components of the dark current (diffusion, recombination and shunt component) indicates that the shunt component is the dominant one at low applied voltage ($V < 300$ mV ). Even at higher voltage ($V >300$ mV ) the shunt component is comparable to the diffusion one when the dislocation density is greater than $10^5$ cm$^{-2}$. The computed results are in agreement with experimental ones.Une analyse détaillée des composantes du courant d'obscurité en polarisation directe dans des jonctions N$^+$ P au silicium multicristallin est proposée. Elle tient compte des dislocations qui traversent la jonction et sa région de charge d'espace. Un modèle a été établi, attribuant une conductibilité aux dislocations. Le courant traversant ces défauts varierait comme $\exp(qV/2 kT)$, et serait le courant dominant aux faibles tensions de polarisation ($V < 300$ mV). Toutefois pour des tensions supérieures à 300 mV, ce courant peut être comparable au courant de diffusion provenant des régions neutres de la jonction, lorsque la densité des dislocations est supérieure à $10^5$ cm$^{-2}$. Les prévisions du modèle sont en bon accord avec les résultats expérimentaux