1,270 research outputs found
Epigenetic Regulation of Neurogenesis By Citron Kinase
No full textPatterns of neural progenitor division are controlled by a combination of asymmetries in cell division, extracellular signals, and changes in gene expression programs. In a screen for proteins that complex with citron kinase (CitK), a protein essential to cell division in developing brain, I identified the histone methyltransferase- euchromatic histone-lysine N-methyltransferse 2 (G9a). CitK is present in the nucleus and binds to positions in the genome clustered around transcription start sites of genes involved in neuronal development and differentiation. CitK and G9a co-occupy these genomic positions in S/G2-phase of the cell cycle in rat neural progenitors, and CitK functions with G9a to repress gene expression in several developmentally important genes including CDKN1a, H2afz, and Pou3f2/Brn2. The study indicates a novel function for citron kinase in gene repression, and contributes additional evidence to the hypothesis that mechanisms that coordinate gene expression states are directly linked to mechanisms that regulate cell division in the developing nervous system
Loss of citron-kinase results in cortical malformation and early-onset epilepsy
No full textDisruptions in the timing and interactions of a single gene or protein can alter the survival and fates of newly generated cells in CNS. In humans these alterations during development can lead to gross malformations of the cerebral cortex and often can be associated with disorders such as epilepsy. In this study, I describe the identification of a novel autosomal recessive mutation in rat, Flathead (fh/fh), which leads to an overall reduction in CNS growth and a cerebral cortex that is one half the size of wildtype. Previous studies in fh/ fh mutants have shown that the fh gene is CNS-specific, and that the reduced brain size correlates with massive apoptosis in proliferative areas during the time of maximal neurogenesis. The group of experiments in this thesis show that homozygous mutants suffer from intractable, spontaneous and high-frequency generalized seizures which begin one week after birth. Throughout the entire cortex of fh/fh mutants, there is a disproportionate loss of inhibitory interneurons which is present before and during the time of seizure generation. Remaining interneurons in fh/fh cortex display dramatic hypertrophy while pyramidal neurons do not show similar changes. The reduction of neocortical interneurons is associated with high levels of cell death in the ganglionic eminence, the primary embryonic source for neocortical interneurons, and the death appears to result from a failed cytokinesis process. Moreover many precursors within the ventricular zone (VZ) are binucleate and binucleate interneurons and pyramidal neurons are observed in postnatal fh/ fh cortex as well. Finally, I show that flathead is caused by a mutation in the first exon of the N-terminal kinase domain in the gene encoding Citron-kinase (Citron-K). Citron-K expression is maximal during neurogenesis and concentrates along the VZ surface where it localizes to cytokinesis furrows and is activated by the small GTPase RhoA. This study shows that Citron-K is required for cytokinesis in neural progenitors and that Citron-K is essential for the survival, fate and differentiation of different cortical neurons. These findings both enhance our understanding of CNS development and provide us with insight into novel pathways which may alter brain excitability and lead to disorders such as epilepsy.
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Hate crimes in cyberspace /
No full textThe author examines the controversies surrounding cyber-harassment, arguing that it should be considered a matter for civil rights law and that social norms of decency and civility must be leveraged to stop it. --Publisher's description.In an in-depth investigation of a problem that is too often trivialized by lawmakers and the media, Citron exposes the startling extent of personal cyber-attacks and proposes practical, lawful ways to prevent and punish online harassment. She reveals the serious emotional, professional, and financial harms incurred by victims. Persistent online attacks disproportionately target women and frequently include detailed fantasies of rape as well as reputation-ruining lies and sexually explicit photographs
Hate crimes in cyberspace /
No full textThe author examines the controversies surrounding cyber-harassment, arguing that it should be considered a matter for civil rights law and that social norms of decency and civility must be leveraged to stop it. --Publisher's description.In an in-depth investigation of a problem that is too often trivialized by lawmakers and the media, Citron exposes the startling extent of personal cyber-attacks and proposes practical, lawful ways to prevent and punish online harassment. She reveals the serious emotional, professional, and financial harms incurred by victims. Persistent online attacks disproportionately target women and frequently include detailed fantasies of rape as well as reputation-ruining lies and sexually explicit photographs
First in the Nation in Education : Final Report,1984.
No full textThis report is one step in an ongoing process of change and is a plea for commitment for high standards in education in Iowa. Contains the final reports of the six subcommittees as adopted by the Excellence in Education Task Force, and the five recommendations made by the Task Force
Les anomalies des voies génitales chez les prostituées qui se douchent en se servant du citron ou du jus de limon au Nigéria
No full textVaginal douche products have been associated with cervical cancer. We
examined female sex workers (FSWs) in Nigeria who douche with lemon or
lime juice and compared the findings with that of nonusers. We obtained
Pap smears and performed colposcopy of the vulva, vagina and cervix. A
total of 374 FSWs comprising 81 Lemon users (LUs) and 293 non lemon
users (NLUs) were examined. Their mean age was 27.8 ± 6.7 (range
16-63) years. At colposcopy, 17(4.5%) had genital warts [LUs 5(6.2%);
NLUs 12(4.1%); p=0.43], 61(16.3%) had suspected squamous
intraepithelial lesions (SILs) [LUs 17(21.0%); NLUs 44(15.0%); p=0.20]
and 65(17.4%) had other findings. Pap smear cytology showed that
87(24.6%) had SILs [LUs 26(33.3%); NLUs 61(22.1%); p=0.03]. Lemon/lime
use was associated with cervical dysplasia after controlling for HIV
status (Adjusted OR=1.8; 95% CI, 1.0-3.0). Our data suggests an
association between the practice of douching with citrus juice and
cervical dysplasia (Afr J Reprod Health 2009; 13[1]:37-45).Les produits de la douche vaginale ont été liés au
cancer du col. Nous avons étudié les prostituées au
Nigéria qui se douchent en se servant du jus de limon et nous les
avons comparées à celles qui ne s’en servent pas. Nous
avons collecté le papanicolaou et nous avons fait la colposcopie
de la vulve, du vagin et du col. Au total, nous avons étudié
374 prostituées qui comprennent 81 qui se servent du citron et 293
qui ne se servent pas du citron. Leur âge moyen s’est
élevé à 27,8 ± 6, 7 (entre 16 et 63 ans). La
colposcopie a montré que 17(4,5%) avaient des verrues
génitales [celles qui se servent du citron = 5(6,2%) ; celles qui
ne s’en servent pas = 12(4,1%) ; p=0,43], 61(16,3% avaient des
lésions intraepitheliales squameuses suspectes (LIS) [celles qui
se servent du citron = 17(21,0%) ; celles qui ne s’en servent pas
= 44(15,0%) ; p = 0,20] et 65 (17,4%) avaient d’autres
résultats. La cytologie du papanicolaou a montré que
87(24,6%) avaient LIS [Celles qui servent du citron = 26(33,3%) ;
celles qui ne s’en servent pas = 61(22,19%) ; p = 0,03].
L’utilisation du citron/du jus de limon a été liée
à la dysplasie cervicale après avoir contrôlé pour
l’état du VIH (OR yiste = 1,8 ; 95% CI, 1,0 – 3,0).
Nos données indiquent un lien entre la pratique de se doucher avec
le jus de limon et la dysplasie cervicale (Afr J Reprod Health 2009;
13[1]:37-45)
Les anomalies des voies génitales chez les prostituées qui se douchent en se servant du citron ou du jus de limon au Nigéria
No full textVaginal douche products have been associated with cervical cancer. We
examined female sex workers (FSWs) in Nigeria who douche with lemon or
lime juice and compared the findings with that of nonusers. We obtained
Pap smears and performed colposcopy of the vulva, vagina and cervix. A
total of 374 FSWs comprising 81 Lemon users (LUs) and 293 non lemon
users (NLUs) were examined. Their mean age was 27.8 ± 6.7 (range
16-63) years. At colposcopy, 17(4.5%) had genital warts [LUs 5(6.2%);
NLUs 12(4.1%); p=0.43], 61(16.3%) had suspected squamous
intraepithelial lesions (SILs) [LUs 17(21.0%); NLUs 44(15.0%); p=0.20]
and 65(17.4%) had other findings. Pap smear cytology showed that
87(24.6%) had SILs [LUs 26(33.3%); NLUs 61(22.1%); p=0.03]. Lemon/lime
use was associated with cervical dysplasia after controlling for HIV
status (Adjusted OR=1.8; 95% CI, 1.0-3.0). Our data suggests an
association between the practice of douching with citrus juice and
cervical dysplasia (Afr J Reprod Health 2009; 13[1]:37-45).Les produits de la douche vaginale ont été liés au
cancer du col. Nous avons étudié les prostituées au
Nigéria qui se douchent en se servant du jus de limon et nous les
avons comparées à celles qui ne s’en servent pas. Nous
avons collecté le papanicolaou et nous avons fait la colposcopie
de la vulve, du vagin et du col. Au total, nous avons étudié
374 prostituées qui comprennent 81 qui se servent du citron et 293
qui ne se servent pas du citron. Leur âge moyen s’est
élevé à 27,8 ± 6, 7 (entre 16 et 63 ans). La
colposcopie a montré que 17(4,5%) avaient des verrues
génitales [celles qui se servent du citron = 5(6,2%) ; celles qui
ne s’en servent pas = 12(4,1%) ; p=0,43], 61(16,3% avaient des
lésions intraepitheliales squameuses suspectes (LIS) [celles qui
se servent du citron = 17(21,0%) ; celles qui ne s’en servent pas
= 44(15,0%) ; p = 0,20] et 65 (17,4%) avaient d’autres
résultats. La cytologie du papanicolaou a montré que
87(24,6%) avaient LIS [Celles qui servent du citron = 26(33,3%) ;
celles qui ne s’en servent pas = 61(22,19%) ; p = 0,03].
L’utilisation du citron/du jus de limon a été liée
à la dysplasie cervicale après avoir contrôlé pour
l’état du VIH (OR yiste = 1,8 ; 95% CI, 1,0 – 3,0).
Nos données indiquent un lien entre la pratique de se doucher avec
le jus de limon et la dysplasie cervicale (Afr J Reprod Health 2009;
13[1]:37-45)
Discovery and Characterization of Selective, First-in-Class Inhibitors of Citron Kinase
No full textCitron
kinase (CITK) is an AGC-family serine/threonine kinase that
regulates cytokinesis. Despite knockdown experiments implicating CITK
as an anticancer target, no selective CITK inhibitors exist. We transformed
a previously reported kinase inhibitor with weak off-target CITK activity
into a first-in-class CITK chemical probe, C3TD879. C3TD879 is a Type I kinase inhibitor which potently inhibits
CITK catalytic activity (biochemical IC50 = 12 nM), binds
directly to full-length human CITK in cells (NanoBRET Kd < 10 nM), and demonstrates favorable DMPK properties
for in vivo evaluation. We engineered exquisite selectivity for CITK
(>17-fold versus 373 other human kinases), making C3TD879 the first chemical probe suitable for interrogating the complex
biology of CITK. Our small-molecule CITK inhibitors could not phenocopy
the effects of CITK knockdown in cell proliferation, cell cycle progression,
or cytokinesis assays, providing preliminary evidence that the structural
roles of CITK may be more important than its kinase activity
Search for millicharged particles at the LHC with the milliQan prototype
No full textWe report on the results of a recent search for fractionally charged particlesusing a data sample of 37.5 proton-proton collisions at TeVprovided by the CERN Large Hadron Collider in 2018. This search was carried out with a prototype scintillator-based detector, which allows the first sensitivity to particles with charges e at a hadron collider. The existence of new particles with masses between 20 and 4700 MeV is excluded at 95\% confidence level for charges between 0.006e and 0.3e, depending on their mass. New sensitivity is achieved for masses larger than 700 MeV. The successful operation of the milliQan prototype provides crucial lessons for the design of the full milliQan detector
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