Dysphagia and disrupted cranial nerve development in a mouse model of DiGeorge (22q11 deletion syndrome

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Beverly A. Karpinski

2014-02-01

Full Text Available We assessed feeding-related developmental anomalies in the LgDel mouse model of chromosome 22q11 deletion syndrome (22q11DS, a common developmental disorder that frequently includes perinatal dysphagia – debilitating feeding, swallowing and nutrition difficulties from birth onward – within its phenotypic spectrum. LgDel pups gain significantly less weight during the first postnatal weeks, and have several signs of respiratory infections due to food aspiration. Most 22q11 genes are expressed in anlagen of craniofacial and brainstem regions critical for feeding and swallowing, and diminished expression in LgDel embryos apparently compromises development of these regions. Palate and jaw anomalies indicate divergent oro-facial morphogenesis. Altered expression and patterning of hindbrain transcriptional regulators, especially those related to retinoic acid (RA signaling, prefigures these disruptions. Subsequently, gene expression, axon growth and sensory ganglion formation in the trigeminal (V, glossopharyngeal (IX or vagus (X cranial nerves (CNs that innervate targets essential for feeding, swallowing and digestion are disrupted. Posterior CN IX and X ganglia anomalies primarily reflect diminished dosage of the 22q11DS candidate gene Tbx1. Genetic modification of RA signaling in LgDel embryos rescues the anterior CN V phenotype and returns expression levels or pattern of RA-sensitive genes to those in wild-type embryos. Thus, diminished 22q11 gene dosage, including but not limited to Tbx1, disrupts oro-facial and CN development by modifying RA-modulated anterior-posterior hindbrain differentiation. These disruptions likely contribute to dysphagia in infants and young children with 22q11DS.

Cross-experimental analysis of coat color variations and morphological characteristics of the japanese wild mouse, Mus musculus.

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Suzuki, Taichi A; Iwasa, Masahiro A

2013-01-01

There are many coat colors in the laboratory mouse, Mus musculus. On the basis of traditional genetics, there are four loci, A-D, related to coat color expressions. As shown by previous studies, Japanese wild mice have gray backs and white bellies and are assumed to carry the A(w) allele at the A (agouti) locus, which is dominant over any other alleles. However, we collected Japanese wild mice from central Honshu with black coats. To understand this black coat expression, we performed cross experiments concerning the four loci using wild-caught mice and DBA/2 laboratory mice from the standpoint of traditional genetics. The offspring of the current crosses showed the wild type, the blackish type, and the intermediate type from some combinations of parents. Considering the coat colors of the offspring, we did not obtain any evidence that the Japanese wild mice always carry the A(w) allele at the A locus. Furthermore, we were not able to explain the current coat color expressions using the traditional logic with regard to the A-D loci and concluded that it is possible for another locus (loci) to be related to the coat color expressions. On the other hand, skull characteristics and external body measurements of the captured wild mice were fundamentally different from those of DBA/2 and offspring from captured wild mice and DBA/2 combinations. Thus, we concluded that the Japanese wild mice had original criteria from a morphological viewpoint.

Oral carcinogenesis is not achieved in different carcinogen-treated PAI-1 transgenic and wild-type mouse models.

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Avgoustidis, Dimitris; Nisyrios, Themistoklis; Nkenke, Emeka; Lijnen, Roger; Ragos, Vassilis; Perrea, Despina; Donta, Ismini; Vaena, Apostolia; Yapijakis, Christos; Vairaktaris, Eleftherios

2012-01-01

In an effort to assess the role of plasminogen activator inhibitor-1 (PAI-1) in oral squamous cancer development and progression, two different carcinogen treatment protocols were conducted. Protocol I included mice from a PAI-1 transgenic (Tg) breed (n=56) and their wild-type (WT) counterparts (n=56), divided into one control group and two main experimental groups, treated with 7,12-dimethylbenz[a]anthracene (DMBA) for 8 and 16 weeks, respectively. Protocol II included the same number and types of animals and groups, which were similarly treated with 4-Nitroquinoline 1-oxide (4-NQO) in drinking water. Two drugs that affect plasma PAI-1 levels, enalapril and pravastatin, were administered to certain subgroups of animals in both protocols. None of the animals developed macroscopically-visible oral cancer lesions. Eleven animals under Protocol I and 52 animals under Protocol II died. Skin lesions were noted only in DMBA-treated animals (n=9). Almost all animals administered with 4-NQO developed alopecia and lost weight, while two of them developed stomach tumours, and one female mouse developed a large ovarian cyst. Transgenic mice may respond differently when used in well-established carcinogen models and oral carcinogenesis is hard to achieve in these rodents.

Chronic activation of wild-type epidermal growth factor receptor and loss of Cdkn2a cause mouse glioblastoma formation.

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Acquaviva, Jaime; Jun, Hyun Jung; Lessard, Julie; Ruiz, Rolando; Zhu, Haihao; Donovan, Melissa; Woolfenden, Steve; Boskovitz, Abraham; Raval, Ami; Bronson, Roderick T; Pfannl, Rolf; Whittaker, Charles A; Housman, David E; Charest, Al

2011-12-01

Glioblastoma multiforme (GBM) is characterized by overexpression of epidermal growth factor receptor (EGFR) and loss of the tumor suppressors Ink4a/Arf. Efforts at modeling GBM using wild-type EGFR in mice have proven unsuccessful. Here, we present a unique mouse model of wild-type EGFR-driven gliomagenesis. We used a combination of somatic conditional overexpression and ligand-mediated chronic activation of EGFR in cooperation with Ink4a/Arf loss in the central nervous system of adult mice to generate tumors with the histopathologic and molecular characteristics of human GBMs. Sustained, ligand-mediated activation of EGFR was necessary for gliomagenesis, functionally substantiating the clinical observation that EGFR-positive GBMs from patients express EGFR ligands. To gain a better understanding of the clinically disappointing EGFR-targeted therapies for GBM, we investigated the molecular responses to EGFR tyrosine kinase inhibitor (TKI) treatment in this model. Gefitinib treatment of primary GBM cells resulted in a robust apoptotic response, partially conveyed by mitogen-activated protein kinase (MAPK) signaling attenuation and accompanied by BIM(EL) expression. In human GBMs, loss-of-function mutations in the tumor suppressor PTEN are a common occurrence. Elimination of PTEN expression in GBM cells posttumor formation did not confer resistance to TKI treatment, showing that PTEN status in our model is not predictive. Together, these findings offer important mechanistic insights into the genetic determinants of EGFR gliomagenesis and sensitivity to TKIs and provide a robust discovery platform to better understand the molecular events that are associated with predictive markers of TKI therapy.

The type III neurofilament peripherin is expressed in the tuberomammillary neurons of the mouse

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Julien Jean-Pierre

2008-02-01

Full Text Available Abstract Background Peripherin, a type III neuronal intermediate filament, is widely expressed in neurons of the peripheral nervous system and in selected central nervous system hindbrain areas with projections towards peripheral structures, such as cranial nerves and spinal cord neurons. Peripherin appears to play a role in neurite elongation during development and axonal regeneration, but its exact function is not known. We noticed high peripherin expression in the posterior hypothalamus of mice, and decided to investigate further the exact location of expression and function of peripherin in the mouse posterior hypothalamus. Results In situ hybridization indicated expression of peripherin in neurons with a distribution reminiscent of the histaminergic neurons, with little signal in any other part of the forebrain. Immunocytochemical staining for histidine decarboxylase and peripherin revealed extensive colocalization, showing that peripherin is produced by histaminergic neurons in all parts of the tuberomammillary nucleus. We next used histamine immunostaining in peripherin knockout, overexpressing and wild type mice to study if altered peripherin expression affects these neurons, but could not detect any visible difference in the appearance of these neurons or their axons. Peripherin knockout mice and heterozygotic littermates were used for measurement of locomotor activity, feeding, drinking, and energy expenditure. Both genotypes displayed diurnal rhythms with all the parameters higher during the dark period. The respiratory quotient, an indicator of the type of substrate being utilized, also exhibited a significant diurnal rhythm in both genotypes. The diurnal patterns and the average values of all the recorded parameters for 24 h, daytime and night time were not significantly different between the genotypes, however. Conclusion In conclusion, we have shown that peripherin is expressed in the tuberomammillary neurons of the mouse

Enhancement of mouse sperm motility by trophinin-binding peptide

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Park Seong

2012-11-01

Full Text Available Abstract Background Trophinin is an intrinsic membrane protein that forms a complex in the cytoplasm with bystin and tastin, linking it microtubule-associated motor dynein (ATPase in some cell types. Previously, we found that human sperm tails contain trophinin, bystin and tastin proteins, and that trophinin-binding GWRQ (glycine, tryptophan, arginine, glutamine peptide enhanced motility of human sperm. Methods Immunohistochemistry was employed to determine trophinin protein in mouse spermatozoa from wild type mouse, by using spermatozoa from trophinin null mutant mice as a negative control. Multivalent 8-branched GWRQ (glycine, tryptophan, arginine, glutamine peptide or GWRQ-MAPS, was chemically synthesized, purified by HPLC and its structure was confirmed by MALDI-TOF mass spectrometry. Effect of GWRQ-MAPS on mouse spermatozoa from wild type and trophinin null mutant was assessed by a computer-assisted semen analyzer (CASA. Results Anti-trophinin antibody stained the principal (central piece of the tail of wild type mouse sperm, whereas the antibody showed no staining on trophinin null sperm. Phage particles displaying GWRQ bound to the principal piece of sperm tail from wild type but not trophinin null mice. GWRQ-MAPS enhanced motility of spermatozoa from wild type but not trophinin null mice. CASA showed that GWRQ-MAPS enhanced both progressive motility and rapid motility in wild type mouse sperm. Conclusions Present study established the expression of trophinin in the mouse sperm tail and trophinin-dependent effect of GWRQ-MAPS on sperm motility. GWRQ causes a significant increase in sperm motility.

PBI creams: a spontaneously mutated mouse strain showing wild animal-type reactivity.

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Hendrie, C A; Van Driel, K S; Talling, J C; Inglis, I R

2001-01-01

PBI creams are mice derived from warfarin-resistant wild stock that has been maintained under laboratory conditions since the 1970s. This study compares their behaviour to that of laboratory mice and wild house and wood mice. Animals were tested in a black/white box and a 2.64x1.4 m runway. In the black/white box, the behaviour of PBI creams was not significantly different from that of house mice and differed most from that of laboratory mice. Notably, the PBI creams showed the greatest activity and escape-orientated behaviours. When animals were approached by the experimenter in the open runway test, the PBI creams had higher flight speeds than both house and wood mice, whilst laboratory mice failed to respond. In the closed runway test where the animals could not escape, the PBI creams, house mice and wood mice all turned and attempted to run past the approaching experimenter, whilst the laboratory mice again failed to react. At the end of this test session, the time taken to catch each animal was recorded. It took less than 5 s to catch laboratory mice but significantly longer to catch the wild strains and the PBI creams (90-100 s for the latter). In these tests, the PBI creams showed wild animal-type reactivity, and as this behaviour has been retained in the laboratory colony for over 30 years, these animals may be useful in the study of the physiological and genetic basis of fear/anxiety in mice.

DNA vaccines encoding proteins from wild-type and attenuated canine distemper virus protect equally well against wild-type virus challenge.

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Nielsen, Line; Jensen, Trine Hammer; Kristensen, Birte; Jensen, Tove Dannemann; Karlskov-Mortensen, Peter; Lund, Morten; Aasted, Bent; Blixenkrone-Møller, Merete

2012-10-01

Immunity induced by DNA vaccines containing the hemagglutinin (H) and nucleoprotein (N) genes of wild-type and attenuated canine distemper virus (CDV) was investigated in mink (Mustela vison), a highly susceptible natural host of CDV. All DNA-immunized mink seroconverted, and significant levels of virus-neutralizing (VN) antibodies were present on the day of challenge with wild-type CDV. The DNA vaccines also primed the cell-mediated memory responses, as indicated by an early increase in the number of interferon-gamma (IFN-γ)-producing lymphocytes after challenge. Importantly, the wild-type and attenuated CDV DNA vaccines had a long-term protective effect against wild-type CDV challenge. The vaccine-induced immunity induced by the H and N genes from wild-type CDV and those from attenuated CDV was comparable. Because these two DNA vaccines were shown to protect equally well against wild-type virus challenge, it is suggested that the genetic/antigenic heterogeneity between vaccine strains and contemporary wild-type strains are unlikely to cause vaccine failure.

The dual PI3K/mTOR inhibitor NVP-BEZ235 induces tumor regression in a genetically engineered mouse model of PIK3CA wild-type colorectal cancer.

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Jatin Roper

Full Text Available To examine the in vitro and in vivo efficacy of the dual PI3K/mTOR inhibitor NVP-BEZ235 in treatment of PIK3CA wild-type colorectal cancer (CRC.PIK3CA mutant and wild-type human CRC cell lines were treated in vitro with NVP-BEZ235, and the resulting effects on proliferation, apoptosis, and signaling were assessed. Colonic tumors from a genetically engineered mouse (GEM model for sporadic wild-type PIK3CA CRC were treated in vivo with NVP-BEZ235. The resulting effects on macroscopic tumor growth/regression, proliferation, apoptosis, angiogenesis, and signaling were examined.In vitro treatment of CRC cell lines with NVP-BEZ235 resulted in transient PI3K blockade, sustained decreases in mTORC1/mTORC2 signaling, and a corresponding decrease in cell viability (median IC(50 = 9.0-14.3 nM. Similar effects were seen in paired isogenic CRC cell lines that differed only in the presence or absence of an activating PIK3CA mutant allele. In vivo treatment of colonic tumor-bearing mice with NVP-BEZ235 resulted in transient PI3K inhibition and sustained blockade of mTORC1/mTORC2 signaling. Longitudinal tumor surveillance by optical colonoscopy demonstrated a 97% increase in tumor size in control mice (p = 0.01 vs. a 43% decrease (p = 0.008 in treated mice. Ex vivo analysis of the NVP-BEZ235-treated tumors demonstrated a 56% decrease in proliferation (p = 0.003, no effects on apoptosis, and a 75% reduction in angiogenesis (p = 0.013.These studies provide the preclinical rationale for studies examining the efficacy of the dual PI3K/mTOR inhibitor NVP-BEZ235 in treatment of PIK3CA wild-type CRC.

Specific and spatial labeling of P0-Cre versus Wnt1-Cre in cranial neural crest in early mouse embryos.

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Chen, Guiqian; Ishan, Mohamed; Yang, Jingwen; Kishigami, Satoshi; Fukuda, Tomokazu; Scott, Greg; Ray, Manas K; Sun, Chenming; Chen, Shi-You; Komatsu, Yoshihiro; Mishina, Yuji; Liu, Hong-Xiang

2017-06-01

P0-Cre and Wnt1-Cre mouse lines have been widely used in combination with loxP-flanked mice to label and genetically modify neural crest (NC) cells and their derivatives. Wnt1-Cre has been regarded as the gold standard and there have been concerns about the specificity of P0-Cre because it is not clear about the timing and spatial distribution of the P0-Cre transgene in labeling NC cells at early embryonic stages. We re-visited P0-Cre and Wnt1-Cre models in the labeling of NC cells in early mouse embryos with a focus on cranial NC. We found that R26-lacZ Cre reporter responded to Cre activity more reliably than CAAG-lacZ Cre reporter during early embryogenesis. Cre immunosignals in P0-Cre and reporter (lacZ and RFP) activity in P0-Cre/R26-lacZ and P0-Cre/R26-RFP embryos was detected in the cranial NC and notochord regions in E8.0-9.5 (4-19 somites) embryos. P0-Cre transgene expression was observed in migrating NC cells and was more extensive in the forebrain and hindbrain but not apparent in the midbrain. Differences in the Cre distribution patterns of P0-Cre and Wnt1-Cre were profound in the midbrain and hindbrain regions, that is, extensive in the midbrain of Wnt1-Cre and in the hindbrain of P0-Cre embryos. The difference between P0-Cre and Wnt1-Cre in labeling cranial NC may provide a better explanation of the differential distributions of their NC derivatives and of the phenotypes caused by Cre-driven genetic modifications. © 2017 Wiley Periodicals, Inc.

Multivariate Analysis of Variance: Finding significant growth in mice with craniofacial dysmorphology caused by the Crouzon mutation

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Thorup, Signe Strann; Ólafsdóttir, Hildur; Darvann, Tron Andre

2010-01-01

Crouzon syndrome is characterized by growth disturbances caused by premature fusion of the cranial growth zones. A mouse model with mutation Fgfr2C342Y, equivalent to the most common Crouzon syndrome mutation (henceforth called the Crouzon mouse model), has a phenotype showing many parallels to t...... used micro-CT scans of 4-week-old mice (N=5) and 6-week-old mice (N=10) with Crouzon syndrome (Fgfr2 C342Y/+) were compared to control groups of 4-week-old wild-type mice (N=5) and 6-week-old wild-type mice (N=10), respectively....

Effects of In Utero Thyroxine Exposure on Murine Cranial Suture Growth.

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R Nicole Howie

Full Text Available Large scale surveillance studies, case studies, as well as cohort studies have identified the influence of thyroid hormones on calvarial growth and development. Surveillance data suggests maternal thyroid disorders (hyperthyroidism, hypothyroidism with pharmacological replacement, and Maternal Graves Disease are linked to as much as a 2.5 fold increased risk for craniosynostosis. Craniosynostosis is the premature fusion of one or more calvarial growth sites (sutures prior to the completion of brain expansion. Thyroid hormones maintain proper bone mineral densities by interacting with growth hormone and aiding in the regulation of insulin like growth factors (IGFs. Disruption of this hormonal control of bone physiology may lead to altered bone dynamics thereby increasing the risk for craniosynostosis. In order to elucidate the effect of exogenous thyroxine exposure on cranial suture growth and morphology, wild type C57BL6 mouse litters were exposed to thyroxine in utero (control = no treatment; low ~167 ng per day; high ~667 ng per day. Thyroxine exposed mice demonstrated craniofacial dysmorphology (brachycranic. High dose exposed mice showed diminished area of the coronal and widening of the sagittal sutures indicative of premature fusion and compensatory growth. Presence of thyroid receptors was confirmed for the murine cranial suture and markers of proliferation and osteogenesis were increased in sutures from exposed mice. Increased Htra1 and Igf1 gene expression were found in sutures from high dose exposed individuals. Pathways related to the HTRA1/IGF axis, specifically Akt and Wnt, demonstrated evidence of increased activity. Overall our data suggest that maternal exogenous thyroxine exposure can drive calvarial growth alterations and altered suture morphology.

Effects of In Utero Thyroxine Exposure on Murine Cranial Suture Growth.

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Howie, R Nicole; Durham, Emily L; Black, Laurel; Bennfors, Grace; Parsons, Trish E; Elsalanty, Mohammed E; Yu, Jack C; Weinberg, Seth M; Cray, James J

2016-01-01

Large scale surveillance studies, case studies, as well as cohort studies have identified the influence of thyroid hormones on calvarial growth and development. Surveillance data suggests maternal thyroid disorders (hyperthyroidism, hypothyroidism with pharmacological replacement, and Maternal Graves Disease) are linked to as much as a 2.5 fold increased risk for craniosynostosis. Craniosynostosis is the premature fusion of one or more calvarial growth sites (sutures) prior to the completion of brain expansion. Thyroid hormones maintain proper bone mineral densities by interacting with growth hormone and aiding in the regulation of insulin like growth factors (IGFs). Disruption of this hormonal control of bone physiology may lead to altered bone dynamics thereby increasing the risk for craniosynostosis. In order to elucidate the effect of exogenous thyroxine exposure on cranial suture growth and morphology, wild type C57BL6 mouse litters were exposed to thyroxine in utero (control = no treatment; low ~167 ng per day; high ~667 ng per day). Thyroxine exposed mice demonstrated craniofacial dysmorphology (brachycranic). High dose exposed mice showed diminished area of the coronal and widening of the sagittal sutures indicative of premature fusion and compensatory growth. Presence of thyroid receptors was confirmed for the murine cranial suture and markers of proliferation and osteogenesis were increased in sutures from exposed mice. Increased Htra1 and Igf1 gene expression were found in sutures from high dose exposed individuals. Pathways related to the HTRA1/IGF axis, specifically Akt and Wnt, demonstrated evidence of increased activity. Overall our data suggest that maternal exogenous thyroxine exposure can drive calvarial growth alterations and altered suture morphology.

Susceptibility of the wild-derived inbred CAST/Ei mouse to infection by orthopoxviruses analyzed by live bioluminescence imaging

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Americo, Jeffrey L.; Sood, Cindy L.; Cotter, Catherine A.; Vogel, Jodi L.; Kristie, Thomas M.; Moss, Bernard; Earl, Patricia L.

2014-01-01

Classical inbred mice are extensively used for virus research. However, we recently found that some wild-derived inbred mouse strains are more susceptible than classical strains to monkeypox virus. Experiments described here indicated that the 50% lethal dose of vaccinia virus (VACV) and cowpox virus (CPXV) were two logs lower in wild-derived inbred CAST/Ei mice than classical inbred BALB/c mice, whereas there was little difference in the susceptibility of the mouse strains to herpes simplex virus. Live bioluminescence imaging was used to follow spread of pathogenic and attenuated VACV strains and CPXV virus from nasal passages to organs in the chest and abdomen of CAST/Ei mice. Luminescence increased first in the head and then simultaneously in the chest and abdomen in a dose-dependent manner. The spreading kinetics was more rapid with VACV than CPXV although the peak photon flux was similar. These data suggest advantages of CAST/Ei mice for orthopoxvirus studies. - Highlights: • Wild-derived inbred CAST/Ei mice are susceptible to vaccinia virus and cowpox virus. • Morbidity and mortality from orthopoxviruses are greater in CAST/Ei than BALB/c mice. • Morbidity and mortality from herpes simplex virus type 1 are similar in both mice. • Imaging shows virus spread from nose to lungs, abdominal organs and brain. • Vaccinia virus spreads more rapidly than cowpox virus

Susceptibility of the wild-derived inbred CAST/Ei mouse to infection by orthopoxviruses analyzed by live bioluminescence imaging

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Americo, Jeffrey L.; Sood, Cindy L.; Cotter, Catherine A.; Vogel, Jodi L.; Kristie, Thomas M.; Moss, Bernard, E-mail: bmoss@nih.gov; Earl, Patricia L., E-mail: pearl@nih.gov

2014-01-20

Classical inbred mice are extensively used for virus research. However, we recently found that some wild-derived inbred mouse strains are more susceptible than classical strains to monkeypox virus. Experiments described here indicated that the 50% lethal dose of vaccinia virus (VACV) and cowpox virus (CPXV) were two logs lower in wild-derived inbred CAST/Ei mice than classical inbred BALB/c mice, whereas there was little difference in the susceptibility of the mouse strains to herpes simplex virus. Live bioluminescence imaging was used to follow spread of pathogenic and attenuated VACV strains and CPXV virus from nasal passages to organs in the chest and abdomen of CAST/Ei mice. Luminescence increased first in the head and then simultaneously in the chest and abdomen in a dose-dependent manner. The spreading kinetics was more rapid with VACV than CPXV although the peak photon flux was similar. These data suggest advantages of CAST/Ei mice for orthopoxvirus studies. - Highlights: • Wild-derived inbred CAST/Ei mice are susceptible to vaccinia virus and cowpox virus. • Morbidity and mortality from orthopoxviruses are greater in CAST/Ei than BALB/c mice. • Morbidity and mortality from herpes simplex virus type 1 are similar in both mice. • Imaging shows virus spread from nose to lungs, abdominal organs and brain. • Vaccinia virus spreads more rapidly than cowpox virus.

Development and Tissue Origins of the Mammalian Cranial Base

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Iseki, S.; Bamforth, S. D.; Olsen, B. R.; Morriss-Kay, G. M.

2008-01-01

The vertebrate cranial base is a complex structure composed of bone, cartilage and other connective tissues underlying the brain; it is intimately connected with development of the face and cranial vault. Despite its central importance in craniofacial development, morphogenesis and tissue origins of the cranial base have not been studied in detail in the mouse, an important model organism. We describe here the location and time of appearance of the cartilages of the chondrocranium. We also examine the tissue origins of the mouse cranial base using a neural crest cell lineage cell marker, Wnt1-Cre/R26R, and a mesoderm lineage cell marker, Mesp1-Cre/R26R. The chondrocranium develops between E11 and E16 in the mouse, beginning with development of the caudal (occipital) chondrocranium, followed by chondrogenesis rostrally to form the nasal capsule, and finally fusion of these two parts via the midline central stem and the lateral struts of the vault cartilages. X-Gal staining of transgenic mice from E8.0 to 10 days post-natal showed that neural crest cells contribute to all of the cartilages that form the ethmoid, presphenoid, and basisphenoid bones with the exception of the hypochiasmatic cartilages. The basioccipital bone and non-squamous parts of the temporal bones are mesoderm derived. Therefore the prechordal head is mostly composed of neural crest-derived tissues, as predicted by the New Head Hypothesis. However, the anterior location of the mesoderm-derived hypochiasmatic cartilages, which are closely linked with the extra-ocular muscles, suggests that some tissues associated with the visual apparatus may have evolved independently of the rest of the “New Head”. PMID:18680740

A Herpes Simplex Virus Type 1 Mutant Expressing a Baculovirus Inhibitor of Apoptosis Gene in Place of Latency-Associated Transcript Has a Wild-Type Reactivation Phenotype in the Mouse

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Jin, Ling; Perng, Guey-Chuen; Mott, Kevin R.; Osorio, Nelson; Naito, Julia; Brick, David J.; Carpenter, Dale; Jones, Clinton; Wechsler, Steven L.

2005-01-01

The latency-associated transcript (LAT) is essential for the wild-type herpes simplex virus type 1 (HSV-1) high-reactivation phenotype since LAT− mutants have a low-reactivation phenotype. We previously reported that LAT can decrease apoptosis and proposed that this activity is involved in LAT's ability to enhance the HSV-1 reactivation phenotype. The first 20% of the primary 8.3-kb LAT transcript is sufficient for enhancing the reactivation phenotype and for decreasing apoptosis, supporting this proposal. For this study, we constructed an HSV-1 LAT− mutant that expresses the baculovirus antiapoptosis gene product cpIAP under control of the LAT promoter and in place of the LAT region mentioned above. Mice were ocularly infected with this mutant, designated dLAT-cpIAP, and the reactivation phenotype was determined using the trigeminal ganglion explant model. dLAT-cpIAP had a reactivation phenotype similar to that of wild-type virus and significantly higher than that of (i) the LAT− mutant dLAT2903; (ii) dLAT1.5, a control virus containing the same LAT deletion as dLAT-cpIAP, but with no insertion of foreign DNA, thereby controlling for potential readthrough transcription past the cpIAP insert; and (iii) dLAT-EGFP, a control virus identical to dLAT-cpIAP except that it contained the enhanced green fluorescent protein open reading frame (ORF) in place of the cpIAP ORF, thereby controlling for expression of a random foreign gene instead of the cpIAP gene. These results show that an antiapoptosis gene with no sequence similarity to LAT can efficiently substitute for the LAT function involved in enhancing the in vitro-induced HSV-1 reactivation phenotype in the mouse. PMID:16160155

Optical coherence tomography imaging of cranial meninges post brain injury in vivo

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Woo June Choi; Ruikang K.Wang

2017-01-01

We report a new application of optical coherence tomography (OCT) to investigate the cranial meninges in an animal model of brain injury in vivo.The injury is induced in a mouse due to skull thinning,in which the repeated and excessive drilling exerts mechanical stress on the mouse brain through the skull,resulting in acute and mild brain injury.Transcranial OCT imaging reveals an interesting virtual space between the cranial meningeal layers post skull thinning,which is gradually closed within hours.The finding suggests a promise of OCT as an effective tool to monitor the mechanical trauma in the small animal model of brain injury.

Comparative Analyses of Transcriptional Profiles in Mouse Organs Using a Pneumonic Plague Model after Infection with Wild-Type Yersinia pestis CO92 and Its Braun Lipoprotein Mutant

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Cristi L. Galindo

2009-01-01

Full Text Available We employed Murine GeneChips to delineate the global transcriptional profiles of the livers, lungs, and spleens in a mouse pneumonic plague infection model with wild-type (WT Y. pestis CO92 and its Braun lipoprotein (Δlpp mutant with reduced virulence. These organs showed differential transcriptional responses to infection with WT Y. pestis, but the overall host functional processes affected were similar across all three tissues. Gene expression alterations were found in inflammation, cytokine signaling, and apoptotic cell death-associated genes. Comparison of WT and Δlpp mutant-infected mice indicated significant overlap in lipopolysaccharide- (LPS- associated gene expression, but the absence of Lpp perturbed host cell signaling at critical regulatory junctions resulting in altered immune response and possibly host cell apoptosis. We generated a putative signaling pathway including major inflammatory components that could account for the synergistic action of LPS and Lpp and provided the mechanistic basis of attenuation caused by deletion of the lpp gene from Y. pestis in a mouse model of pneumonic plague.

Type II iodothyronine deiodinase provides intracellular 3,5,3′-triiodothyronine to normal and regenerating mouse skeletal muscle

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Marsili, Alessandro; Tang, Dan; Harney, John W.; Singh, Prabhat; Zavacki, Ann Marie; Dentice, Monica; Salvatore, Domenico

2011-01-01

The FoxO3-dependent increase in type II deiodinase (D2), which converts the prohormone thyroxine (T4) to 3,5,3′-triiodothyronine (T3), is required for normal mouse skeletal muscle differentiation and regeneration. This implies a requirement for an increase in D2-generated intracellular T3 under these conditions, which has not been directly demonstrated despite the presence of D2 activity in skeletal muscle. We directly show that D2-mediated T4-to-T3 conversion increases during differentiation in C2C12 myoblast and primary cultures of mouse neonatal skeletal muscle precursor cells, and that blockade of D2 eliminates this. In adult mice given 125I-T4 and 131I-T3, the intracellular 125I-T3/131I-T3 ratio is significantly higher than in serum in both the D2-expressing cerebral cortex and the skeletal muscle of wild-type, but not D2KO, mice. In D1-expressing liver and kidney, the 125I-T3/131I-T3 ratio does not differ from that in serum. Hypothyroidism increases D2 activity, and in agreement with this, the difference in 125I-T3/131I-T3 ratio is increased further in hypothyroid wild-type mice but not altered in the D2KO. Notably, in wild-type but not in D2KO mice, the muscle production of 125I-T3 is doubled after skeletal muscle injury. Thus, D2-mediated T4-to-T3 conversion generates significant intracellular T3 in normal mouse skeletal muscle, with the increased T3 required for muscle regeneration being provided by increased D2 synthesis, not by T3 from the circulation. PMID:21771965

Spatial encoding in spinal sensorimotor circuits differs in different wild type mice strains

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Schouenborg Jens

2008-05-01

Full Text Available Abstract Background Previous studies in the rat have shown that the spatial organisation of the receptive fields of nociceptive withdrawal reflex (NWR system are functionally adapted through experience dependent mechanisms, termed somatosensory imprinting, during postnatal development. Here we wanted to clarify 1 if mice exhibit a similar spatial encoding of sensory input to NWR as previously found in the rat and 2 if mice strains with a poor learning capacity in various behavioural tests, associated with deficient long term potention, also exhibit poor adaptation of NWR. The organisation of the NWR system in two adult wild type mouse strains with normal long term potentiation (LTP in hippocampus and two adult wild type mouse strains exhibiting deficiencies in corresponding LTP were used and compared to previous results in the rat. Receptive fields of reflexes in single hindlimb muscles were mapped with CO2 laser heat pulses. Results While the spatial organisation of the nociceptive receptive fields in mice with normal LTP were very similar to those in rats, the LTP impaired strains exhibited receptive fields of NWRs with aberrant sensitivity distributions. However, no difference was found in NWR thresholds or onset C-fibre latencies suggesting that the mechanisms determining general reflex sensitivity and somatosensory imprinting are different. Conclusion Our results thus confirm that sensory encoding in mice and rat NWR is similar, provided that mice strains with a good learning capability are studied and raise the possibility that LTP like mechanisms are involved in somatosensory imprinting.

Marked seasonal variation in the wild mouse gut microbiota.

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Maurice, Corinne F; Knowles, Sarah C L; Ladau, Joshua; Pollard, Katherine S; Fenton, Andy; Pedersen, Amy B; Turnbaugh, Peter J

2015-11-01

Recent studies have provided an unprecedented view of the microbial communities colonizing captive mice; yet the host and environmental factors that shape the rodent gut microbiota in their natural habitat remain largely unexplored. Here, we present results from a 2-year 16 S ribosomal RNA gene sequencing-based survey of wild wood mice (Apodemus sylvaticus) in two nearby woodlands. Similar to other mammals, wild mice were colonized by 10 bacterial phyla and dominated by the Firmicutes, Bacteroidetes and Proteobacteria. Within the Firmicutes, the Lactobacillus genus was most abundant. Putative bacterial pathogens were widespread and often abundant members of the wild mouse gut microbiota. Among a suite of extrinsic (environmental) and intrinsic (host-related) factors examined, seasonal changes dominated in driving qualitative and quantitative differences in the gut microbiota. In both years examined, we observed a strong seasonal shift in gut microbial community structure, potentially due to the transition from an insect- to a seed-based diet. This involved decreased levels of Lactobacillus, and increased levels of Alistipes (Bacteroidetes phylum) and Helicobacter. We also detected more subtle but statistically significant associations between the gut microbiota and biogeography, sex, reproductive status and co-colonization with enteric nematodes. These results suggest that environmental factors have a major role in shaping temporal variations in microbial community structure within natural populations.

Cerebellar Expression of the Neurotrophin Receptor p75 in Naked-Ataxia Mutant Mouse

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Maryam Rahimi Balaei

2016-01-01

Full Text Available Spontaneous mutation in the lysosomal acid phosphatase 2 (Acp2 mouse (nax—naked-ataxia mutant mouse correlates with severe cerebellar defects including ataxia, reduced size and abnormal lobulation as well as Purkinje cell (Pc degeneration. Loss of Pcs in the nax cerebellum is compartmentalized and harmonized to the classic pattern of gene expression of the cerebellum in the wild type mouse. Usually, degeneration starts in the anterior and posterior zones and continues to the central and nodular zones of cerebellum. Studies have suggested that the p75 neurotrophin receptor (NTR plays a role in Pc degeneration; thus, in this study, we investigated the p75NTR pattern and protein expression in the cerebellum of the nax mutant mouse. Despite massive Pc degeneration that was observed in the nax mouse cerebellum, p75NTR pattern expression was similar to the HSP25 pattern in nax mice and comparable with wild type sibling cerebellum. In addition, immunoblot analysis of p75NTR protein expression did not show any significant difference between nax and wild type sibling (p > 0.5. In comparison with wild type counterparts, p75NTR pattern expression is aligned with the fundamental cytoarchitecture organization of the cerebellum and is unchanged in the nax mouse cerebellum despite the severe neurodevelopmental disorder accompanied with Pc degeneration.

Impairment of Vision in a Mouse Model of Usher Syndrome Type III.

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Tian, Guilian; Lee, Richard; Ropelewski, Philip; Imanishi, Yoshikazu

2016-03-01

The purpose of this study was to obtain an Usher syndrome type III mouse model with retinal phenotype. Speed congenic method was used to obtain Clrn1 exon 1 knockout (Clrn1-/-) and Clrn1N48K knockin (Clrn1N48K/N48K) mice under A/J background. To study the retinal functions of these mice, we measured scotopic and photopic ERG responses. To observe if there are any structural abnormalities, we conducted light and transmission electron microscopy of fixed retinal specimens. In 3-month-old Clrn1-/- mice, scotopic b-wave amplitude was reduced by more than 25% at the light intensities from -2.2 to 0.38 log cd·s/m2, but scotopic a-wave amplitudes were comparable to those of age-matched wild type mice at all the light intensities tested. In 9-month-old Clrn1-/- mice, scotopic b-wave amplitudes were further reduced by more than 35%, and scotopic a-wave amplitude also showed a small decline as compared with wild type mice. Photopic ERG responses were comparable between Clrn1-/- and wild type mice. Those electrophysiological defects were not associated with a loss of rods. In Clrn1N48K/N48K mice, both a- and b-wave amplitudes were not discernable from those of wild type mice aged up to 10 months. Mutations that are Clrn1-/- biallelic cause visual defects when placed under A/J background. The absence of apparent rod degeneration suggests that the observed phenotype is due to functional defects, and not due to loss of rods. Biallelic Clrn1N48K/N48K mutations did not cause discernible visual defects, suggesting that Clrn1- allele is more severely dysfunctional than ClrnN48K allele.

Robo signaling regulates the production of cranial neural crest cells.

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Li, Yan; Zhang, Xiao-Tan; Wang, Xiao-Yu; Wang, Guang; Chuai, Manli; Münsterberg, Andrea; Yang, Xuesong

2017-12-01

Slit/Robo signaling plays an important role in the guidance of developing neurons in developing embryos. However, it remains obscure whether and how Slit/Robo signaling is involved in the production of cranial neural crest cells. In this study, we examined Robo1 deficient mice to reveal developmental defects of mouse cranial frontal and parietal bones, which are derivatives of cranial neural crest cells. Therefore, we determined the production of HNK1 + cranial neural crest cells in early chick embryo development after knock-down (KD) of Robo1 expression. Detection of markers for pre-migratory and migratory neural crest cells, PAX7 and AP-2α, showed that production of both was affected by Robo1 KD. In addition, we found that the transcription factor slug is responsible for the aberrant delamination/EMT of cranial neural crest cells induced by Robo1 KD, which also led to elevated expression of E- and N-Cadherin. N-Cadherin expression was enhanced when blocking FGF signaling with dominant-negative FGFR1 in half of the neural tube. Taken together, we show that Slit/Robo signaling influences the delamination/EMT of cranial neural crest cells, which is required for cranial bone development. Copyright © 2017. Published by Elsevier Inc.

Comparative analysis of morphogeometric parameters of forward cranial pole depending on type of a skull basis

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Aleshkina О.Yu.

2012-03-01

Full Text Available The purpose of the work is comparison of parameters of a forward cranial pole depending on type of a skull basis. The research material contained 100 adult skulls divided into three craniotypes. The method of craniotopometry was used for measuring the parameters and further calculation of average value and their comparison among themselves. Results. The research helped to reveal that length of a forward cranial pole, length of a lateral part on the right and at the left, a corner f.c.-s-n prevail at flexibasilar craniotype. Conclusions. The width of a forward cranial pole, width of a lateral part on the right and at the left, a corner f.c.-n-g are more at platibasilar craniotype

Dietary Calcium and Dairy Modulation of Oxidative Stress and Mortality in aP2-Agouti and Wild-type Mice

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Antje Bruckbauer

2009-08-01

Full Text Available Oxidative and inflammatory stress have been implicated as major contributors to the aging process. Dietary Ca reduced both factors in short-term interventions, while milk exerted a greater effect than supplemental Ca. In this work, we examined the effects of life-long supplemental and dairy calcium on lifespan and life-span related biomarkers in aP2-agouti transgenic (model of diet-induced obesity and wild-type mice fed obesigenic diets until their death. These data demonstrate that dairy Ca exerts sustained effects resulting in attenuated adiposity, protection against age-related muscle loss and reduction of oxidative and inflammatory stress in both mouse strains. Although these effects did not alter maximum lifespan, they did suppress early mortality in wild-type mice, but not in aP2-agouti transgenic mice.

Voltage-dependent ion channels in the mouse RPE: comparison with Norrie disease mice.

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Wollmann, Guido; Lenzner, Steffen; Berger, Wolfgang; Rosenthal, Rita; Karl, Mike O; Strauss, Olaf

2006-03-01

We studied electrophysiological properties of cultured retinal pigment epithelial (RPE) cells from mouse and a mouse model for Norrie disease. Wild-type RPE cells revealed the expression of ion channels known from other species: delayed-rectifier K(+) channels composed of Kv1.3 subunits, inward rectifier K(+) channels, Ca(V)1.3 L-type Ca(2+) channels and outwardly rectifying Cl(-) channels. Expression pattern and the ion channel characteristics current density, blocker sensitivity, kinetics and voltage-dependence were compared in cells from wild-type and Norrie mice. Although no significant differences were observed, our study provides a base for future studies on ion channel function and dysfunction in transgenic mouse models.

Functional analysis in mouse embryonic stem cells reveals wild-type activity for three MSH6 variants found in suspected Lynch syndrome patients.

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Eva A L Wielders

Full Text Available Lynch syndrome confers an increased risk to various types of cancer, in particular early onset colorectal and endometrial cancer. Mutations in mismatch repair (MMR genes underlie Lynch syndrome, with the majority of mutations found in MLH1 and MSH2. Mutations in MSH6 have also been found but these do not always cause a clear cancer predisposition phenotype and MSH6-defective tumors often do not show the standard characteristics of MMR deficiency, such as microsatellite instability. In particular, the consequences of MSH6 missense mutations are challenging to predict, which further complicates genetic counseling. We have previously developed a method for functional characterization of MSH2 missense mutations of unknown significance. This method is based on endogenous gene modification in mouse embryonic stem cells using oligonucleotide-directed gene targeting, followed by a series of functional assays addressing the MMR functions. Here we have adapted this method for the characterization of MSH6 missense mutations. We recreated three MSH6 variants found in suspected Lynch syndrome families, MSH6-P1087R, MSH6-R1095H and MSH6-L1354Q, and found all three to behave like wild type MSH6. Thus, despite suspicion for pathogenicity from clinical observations, our approach indicates these variants are not disease causing. This has important implications for counseling of mutation carriers.

Terminal nerve: cranial nerve zero

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Jorge Eduardo Duque Parra

2006-12-01

Full Text Available It has been stated, in different types of texts, that there are only twelve pairs of cranial nerves. Such texts exclude the existence of another cranial pair, the terminal nerve or even cranial zero. This paper considers the mentioned nerve like a cranial pair, specifying both its connections and its functional role in the migration of liberating neurons of the gonadotropic hormone (Gn RH. In this paper is also stated the hypothesis of the phylogenetic existence of a cerebral sector and a common nerve that integrates the terminal nerve with the olfactory nerves and the vomeronasals nerves which seem to carry out the odors detection function as well as in the food search, pheromone detection and nasal vascular regulation.

Cranial vault remodeling in microcephalic osteodysplastic primordial dwarfism type II and craniosynostosis.

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Engel, Michael; Castrillon-Oberndorfer, Gregor; Hoffmann, Jürgen; Egermann, Marcus; Freudlsperger, Christian; Thiele, Oliver Christian

2012-09-01

This is a survey of the long-term result after various surgical treatments in a child with microcephalic osteodysplastic primordial dwarfism type II (MOPD II) and craniosynostosis. We report a 17-year-old patient with MOPD II but some unusual clinical signs including bilateral knee dislocation, a misplaced upper lobe bronchus, and hypoplasia of the anterior corpus callosum. Because of premature fusion of several cranial sutures, the child developed signs of increased intracranial pressure with somnolence and papilledema. Cranial vault remodeling with fronto-orbital advancement was performed twice at the age of 16 and 21 months to open the abnormally closed suture, increase the intracranial volume, and relieve the elevated intracranial pressure. Following this procedure, the child's neurologic situation recovered significantly. Surgical procedure of fronto-orbital advancement and the performed reoperation in our patient were safe with no major complications intraoperatively and postoperatively with good functional and satisfying aesthetic outcomes in the long-term follow-up, expressed by the patient, his parents, and the surgeons.

Glucocorticoid-regulated and constitutive trafficking of proteolytically processed cell surface-associated glycoproteins in wild type and variant rat hepatoma cells

International Nuclear Information System (INIS)

Amacher, S.L.; Goodman, L.J.; Bravo, D.A.; Wong, K.Y.; Goldfine, I.D.; Hawley, D.M.; Firestone, G.L.

1989-01-01

Glucocorticoids regulate the trafficking of mouse mammary tumor virus (MMTV) glycoproteins to the cell surface in the rat hepatoma cell line M1.54, but not in the immunoselected sorting variant CR4. To compare the localization of MMTV glycoproteins to another proteolytically processed glycoprotein, both wild type M1.54 cells and variant CR4 cells were transfected with a human insulin receptor (hIR) expression vector, pRSVhIR. The production of cell surface hIR was monitored in dexamethasone-treated and -untreated wild type M1.54 and variant CR4 cells by indirect immunofluorescence, direct plasma membrane immunoprecipitation, and by [125I] insulin binding. In both wild type and variant rat hepatoma cells, hIR were localized at the cell surface in the presence or in the absence of 1 microM dexamethasone. In contrast, the glucocorticoid-regulated trafficking of cell surface MMTV glycoproteins occurred only in wild type M1.54 cells. We conclude that the hIR, which undergoes posttranslational processing reactions similar to MMTV glycoproteins, does not require glucocorticoids to be transported to the plasma membrane and is representative of a subset of cell surface glycoproteins whose trafficking is constitutive in rat hepatoma cells. Thus, MMTV glycoproteins and hIR provide specific cell surface markers to characterize the glucocorticoid-regulated and constitutive sorting pathways

Mitochondrial energy metabolism changes during aging-mouse cranial nerve cells treated with various doses and forms of Fructus schizandrae

Institute of Scientific and Technical Information of China (English)

Hongyan Guo; Jinhe Li

2008-01-01

BACKGROUND: During the cellular aging process, the number of mitochondria, generation of adenosine triphosphate (ATP), activity of respiratory chain enzyme complex 1 and 4, and oxidation decrease. OBJECTIVE: To observe the effects of aqueous and spirituous extract, as well as polysaccharides from Fructus schizandrae (Magnolia Vine) on energy metabolism and mitochondrial anti-oxidation in cranial nerve cells of a D-gal-induccd aging mouse model.DESIGN, TIME AND SETTING: A randomized, controlled, animal study. The experiment was conducted at the Department of Biochemistry, Qiqihar Medical College between March and July 2006.MATERIALS: Fifty healthy, Kunming mice of both sexes, aged 2 3 months old and weighing 18-22 g, were used for the present study. Fructus schizandrae was purchased from the Medical College of Jiamusi University. Aqueous extracts, spirituous extracts, and polysaccharides from Fructus schizandrae were prepared. D-galactose (D-gal) is a product of the Second Reagent Factory, Shanghai City, China. Mn-superoxide dismutase (Mn-SOD) kit, malonaldehyde (MDA) kit, protein quantification kit, and inorganic phosphorus testing kit were purchased from Jian Cheng Bioeng. Co., China.METHODS: Fifty mice were randomly divided into five groups, with 10 mice in each group: young control, aging model, aqueous Fructus schizandrae extract, spirituous Fructus schizandrae extract, and Fructus schizandrae polysaccharides. Over a course of 30 days, mice in aging model, aqueous Fructus schizandrae extract, spirituous Fructus schizandrae extract, and Fructus schizandrae polysaccharides groups were injected subcutaneously with D-gal (100 mg/kg) into the nape of the neck daily, and administered intragastrically with an equal volume of sterile, warm water (aging model), aqueous Fructus schizandrae extract (2 g/kg), spirituous Fructus schizandrae extract (2 g/kg), or Fructus schizandrae polysaccharides (0.2 g/kg), respectively. Mice in the young control group were injected into

Does Peripheral Neuropathy Associate with Cranial Nerves Neuropathy in Type 2 diabetes Patients?

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Walaa Fadhil Jalal

2017-02-01

Full Text Available Diabetic peripheral neuropathy (DPN is the most common complication of type 2 diabetes mellitus. Cranial neuropathies is usually presenting as mononeuropathies coexist with DPN either presented clinically or in subclinical form. The aim of this study is to detect cranial neuropathy in diabetic patients. Eighty three patients with type 2 diabetes mellitus (T2DM with an age range of 30-69 years were included in the study. The study also involved normal healthy persons whose age and gender are harmonized with that of our patients that were deliberated as control group (60 persons. Diabetic patients with DPN had significant difference in age, highly significant difference in the duration of the disease and highly significance difference in BMI had poor glycemic control reflected by high FBS and HbA1c, while lipid profile picture showed insignificant difference when compared with diabetic patients without DPN. Nerve conduction study (sensory and motor showed a significant difference regarding latency, amplitude, and conduction velocity between diabetic patients with DPN and those without DPN. The results of blink reflex showed highly significant difference between diabetic patients and controls.

[Establishment of EL4 tumor-bearing mouse models and investigation on immunological mechanisms of anti-tumor effect of melphalan].

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Li, Mo-lin; Li, Chuan-gang; Shu, Xiao-hong; Jia, Yu-jie; Qin, Zhi-hai

2006-03-01

To establish mouse lymphoma EL4 tumor-bearing mouse models in wild type C57BL/6 mice and nude C57BL/6 mice respectively, and to further investigate the immunological mechanisms of anti-tumor effect of melphalan. Mouse lymphoma EL4 cells were inoculated subcutaneously into wild type C57BL/6 mice (immune-competent mice). Twelve days later, melphalan of different doses were administered intraperitoneally to treat these wild type C57BL/6 tuomr-bearing mice. Tumor sizes were observed and recorded subsequently to find out the minimal dose of melphalan that could cure the tuomr-bearing mice. Then the same amount of EL4 tumor cells were inoculated subcutaneously into wild type C57BL/6 mice and nude C57BL/6 mice (T cell-deficient mice) simultaneously, which had the same genetic background of C57BL/6. Twelve days later, melphalan of the minimal dose was given intraperitoneally to treat both the wild type and nude C57BL/6 tuomr-bearing mice. Tumor sizes were observed and recorded in these two different types of mice subsequently. A single dose of melphalan (7.5 mg/kg) could cure EL4 tumor-bearing wild type C57BL/6 mice, but could not induce tumor regression in EL4 tumor-bearing nude C57BL/6 mice. A single dose of melphalan has obvious anti-tumor effect on mouse lymphoma EL4 tumor-bearing wild type C57BL/6mice, which requires the involvement of T lymphocytes in the host probably related to their killing functions.

Comparison of the Tastes of L-Alanine and Monosodium Glutamate in C57BL/6J Wild Type and T1r3 Knockout Mice.

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Eddy, Meghan C; Eschle, Benjamin K; Delay, Eugene R

2017-09-01

Previous research showed that L-alanine and monosodium L-glutamate elicit similar taste sensations in rats. This study reports the results of behavioral experiments designed to compare the taste capacity of C57BL/6J wild type and T1r3- mice for these 2 amino acids. In conditioned taste aversion (CTA) experiments, wild-type mice exhibited greater sensitivity than knockout mice for both L-amino acids, although knockout mice were clearly able to detect both amino acids at 50 mM and higher concentrations. Generalization of CTA between L-alanine and L-glutamate was bidirectionally equivalent for both mouse genotypes, indicating that both substances elicited similar tastes in both genotypes. This was verified by the discrimination experiments in which both mouse genotypes performed at or near chance levels at 75 and 150 mM. Above 150 mM, discrimination performance improved, suggesting the taste qualities of the 2 L-amino acids are not identical. No differences between knockout and wild-type mice in discrimination ability were detected. These results indicate that while the T1r3 receptor is important for tasting L-alanine and L-glutamate, other receptors are also important for tasting these amino acids. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Sodium homeostasis is preserved in a global 11β-hydroxysteroid dehydrogenase type 1 knockout mouse model

DEFF Research Database (Denmark)

Christensen, Thorbjørn H; Bailey, Matthew A; Kenyon, Christopher J

2015-01-01

hypothesized that loss of renal 11βHSD1 would result in salt wasting and tested this in a knockout mouse model in which 11βHSD1 was deleted in all body tissues. In balance studies, 11βHSD1 deletion had no effect on water, sodium or potassium metabolism; transition to a low-sodium diet did not reveal...... that global deletion of 11βHSD1 in the mouse would give rise to a salt-wasting renal phenotype. What is the main finding and its importance? We subjected a mouse model of global 11βHSD1 deletion to studies of water and electrolyte balance, renal clearance, urinary steroid excretion, renin-angiotensin system...... a natriuretic phenotype. Renal clearance studies demonstrated identical haemodynamic parameters (arterial blood pressure, renal blood flow and glomerular filtration rate) in knockout and wild-type mice, but revealed an augmented kaliuretic response to thiazides in 11βHSD1 knockout animals. There was no effect...

Black bear parathyroid hormone has greater anabolic effects on trabecular bone in dystrophin-deficient mice than in wild type mice.

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Gray, Sarah K; McGee-Lawrence, Meghan E; Sanders, Jennifer L; Condon, Keith W; Tsai, Chung-Jui; Donahue, Seth W

2012-09-01

Duchenne muscular dystrophy (DMD) is an X-linked neuromuscular disease that has deleterious consequences in muscle and bone, leading to decreased mobility, progressive osteoporosis, and premature death. Patients with DMD experience a higher-than-average fracture rate, particularly in the proximal and distal femur and proximal tibia. The dystrophin-deficient mdx mouse is a model of DMD that demonstrates muscle degeneration and fibrosis and osteoporosis. Parathyroid hormone, an effective anabolic agent for post-menopausal and glucocorticoid-induced osteoporosis, has not been explored for DMD. Black bear parathyroid hormone (bbPTH) has been implicated in the maintenance of bone properties during extended periods of disuse (hibernation). We cloned bbPTH and found 9 amino acid residue differences from human PTH. Apoptosis was mitigated and cAMP was activated by bbPTH in osteoblast cultures. We administered 28nmol/kg of bbPTH 1-84 to 4-week old male mdx and wild type mice via daily (5×/week) subcutaneous injection for 6 weeks. Vehicle-treated mdx mice had 44% lower trabecular bone volume fraction than wild type mice. No changes were found in femoral cortical bone geometry or mechanical properties with bbPTH treatment in wild type mice, and only medio-lateral moment of inertia changed with bbPTH treatment in mdx femurs. However, μCT analyses of the trabecular regions of the distal femur and proximal tibia showed marked increases in bone volume fraction with bbPTH treatment, with a greater anabolic response (7-fold increase) in mdx mice than wild type mice (2-fold increase). Trabecular number increased in mdx long bone, but not wild type bone. Additionally, greater osteoblast area and decreased osteoclast area were observed with bbPTH treatment in mdx mice. The heightened response to PTH in mdx bone compared to wild type suggests a link between dystrophin deficiency, altered calcium signaling, and bone. These findings support further investigation of PTH as an anabolic

Evaluation of MIC Strip Isavuconazole test for susceptibility testing of wild-type and non-wild-type Aspergillus fumigatus isolates

DEFF Research Database (Denmark)

Arendrup, Maiken Cavling; Verweij, Paul; Nielsen, Henrik Vedel

2017-01-01

We evaluated the MIC Strip Isavuconazole test against EUCAST E.Def 9.3 by using 40 wild-type and 39 CYP51A mutant Aspergillus fumigatus strains. The strip full inhibition endpoint (FIE) and 80% growth inhibition endpoint were determined by two independent readers, reader 1 (R1) and R2. The essent......We evaluated the MIC Strip Isavuconazole test against EUCAST E.Def 9.3 by using 40 wild-type and 39 CYP51A mutant Aspergillus fumigatus strains. The strip full inhibition endpoint (FIE) and 80% growth inhibition endpoint were determined by two independent readers, reader 1 (R1) and R2...

Homology of the cranial vault in birds: new insights based on embryonic fate-mapping and character analysis

Science.gov (United States)

Maddin, Hillary C.; Piekarski, Nadine; Sefton, Elizabeth M.; Hanken, James

2016-08-01

Bones of the cranial vault appear to be highly conserved among tetrapod vertebrates. Moreover, bones identified with the same name are assumed to be evolutionarily homologous. However, recent developmental studies reveal a key difference in the embryonic origin of cranial vault bones between representatives of two amniote lineages, mammals and birds, thereby challenging this view. In the mouse, the frontal is derived from cranial neural crest (CNC) but the parietal is derived from mesoderm, placing the CNC-mesoderm boundary at the suture between these bones. In the chicken, this boundary is located within the frontal. This difference and related data have led several recent authors to suggest that bones of the avian cranial vault are misidentified and should be renamed. To elucidate this apparent conflict, we fate-mapped CNC and mesoderm in axolotl to reveal the contributions of these two embryonic cell populations to the cranial vault in a urodele amphibian. The CNC-mesoderm boundary in axolotl is located between the frontal and parietal bones, as in the mouse but unlike the chicken. If, however, the avian frontal is regarded instead as a fused frontal and parietal (i.e. frontoparietal) and the parietal as a postparietal, then the cranial vault of birds becomes developmentally and topologically congruent with those of urodeles and mammals. This alternative hypothesis of cranial vault homology is also phylogenetically consistent with data from the tetrapod fossil record, where frontal, parietal and postparietal bones are present in stem lineages of all extant taxa, including birds. It further implies that a postparietal may be present in most non-avian archosaurs, but fused to the parietal or supraoccipital as in many extant mammals.

UV-sensitivity and repair of UV-damage in Salmonella of wild type

International Nuclear Information System (INIS)

Kondratiev, Y.S.; Brukhansky, G.V.; Andreeva, I.V.; Skavronskaya, A.G.

1977-01-01

The UV-sensitivity of wild type Salmonella strains has been compared to that of wild type E.coli and its UV-sensitive mutants. Many wild type Salmonella strains are 4-5 times more sensitive than wild type E.coli and their inactivation curve is similar to that for E.coli with a mutation in the polA gene. Alkaline sucrose gradient centrifugation has shown a deficiency of these strains in normal excision repair of UV-damaged DNA. This deficiency is not a Salmonella genus feature because one strain as resistant as wild type E.coli was found. This resistant strain showed normal excision repair in alkaline sucrose gradient centrifugation experiments. The possible influence of plasmids and mutations in repair genes on the ability of Salmonella to repair UV-damaged DNA is discussed. (orig.) [de

UV-sensitivity and repair of UV-damage in Salmonella of wild type

Energy Technology Data Exchange (ETDEWEB)

Kondratiev, Y S; Brukhansky, G V; Andreeva, I V; Skavronskaya, A G [Akademiya Meditsinskikh Nauk SSSR, Moscow. Inst. Ehpidemiologii i Mikrobiologii

1977-12-01

The UV-sensitivity of wild type Salmonella strains has been compared to that of wild type E.coli and its UV-sensitive mutants. Many wild type Salmonella strains are 4-5 times more sensitive than wild type E.coli and their inactivation curve is similar to that for E.coli with a mutation in the polA gene. Alkaline sucrose gradient centrifugation has shown a deficiency of these strains in normal excision repair of UV-damaged DNA. This deficiency is not a Salmonella genus feature because one strain as resistant as wild type E.coli was found. This resistant strain showed normal excision repair in alkaline sucrose gradient centrifugation experiments. The possible influence of plasmids and mutations in repair genes on the ability of Salmonella to repair UV-damaged DNA is discussed.

Sabin and wild type polioviruses from children who presented with ...

African Journals Online (AJOL)

Conclusion: This study further confirms the presence of Sabin and wild-type poliovirus among children in Nigeria. The isolation of Sabin strain of poliovirus is advantageous to the polio eradication program as it is capable of inducing natural immunity in susceptible hosts. Transmission of wild-type poliovirus among children ...

Phospholipase C δ-type consists of three isozymes: bovine PLCδ2 is a homologue of human/mouse PLCδ4

International Nuclear Information System (INIS)

Irino, Yasuhiro; Cho, Hiroyuki; Nakamura, Yoshikazu; Nakahara, Masamichi; Furutani, Masahiro; Suh, Pann-Ghill; Takenawa, Tadaomi; Fukami, Kiyoko

2004-01-01

To date, 12 phospholipase C (PLC) isozymes have been identified in mammals, and they are divided into five classes, β-, γ-, δ-, ε-, and ζ-type. PLCδ-type is reported to be composed of four isozymes, PLCδ1-δ4. Here we report that a screening for mouse PLCδ2 from a BAC library with primers that amplify a specific region of bovine PLCδ2 resulted in isolation of one clone containing the mouse PLCδ4 gene. Furthermore, a database search revealed that there is only one gene corresponding to PLCδ2 and PLCδ4 in the mouse and human genomes, indicating that bovine PLCδ2 is a homologue of human and mouse PLCδ4. However, PLCδ2 Western blot analysis with a widely used commercial anti-PLCδ2 antibody showed an expression pattern distinct from that of PLCδ4 in wild-type mice. In addition, an 80-kDa band, which was recognized by antibody against PLCδ2, was smaller than an 85-kDa band detected by anti-PLCδ4 antibody, and the 80-kDa band was detectable in lysates of brain, testis, and spleen from PLCδ4-deficient mice. We also found that immunoprecipitates from brain lysates with this PLCδ2 antibody contained no PLC activity. From these data, we conclude that bovine PLCδ2 is a homologue of human and mouse PLCδ4, and that three isozymes (δ1, δ3, and δ4) exist in the PLCδ family

The formation and repair of cisplatin-DNA adducts in wild-type and cisplatin-resistant L1210 cells : comparison of immunocytochemical determination with detection in isolated DNA

NARCIS (Netherlands)

Blommaert, F.A.; Floot, B.G.J.; Dijk-Knijnenburg, H.C.M. van; Berends, F.; Baan, R.A.; Schornagel, J.H.; Engelse, L. den; Fichtinger-Schepman, A.M.J.

1998-01-01

We have studied the formation and repair of cisplatin-DNA adducts in wild-type mouse leukemia L1210/0 cells and in the sublines L1210/2 and L1210/5, which differ in cisplatin sensitivity. In a colony-formation assay these sublines were 9- and 22-fold more resistant compared to L1210/0, respectively.

Mouse adenovirus type 1 infection of macrophages

NARCIS (Netherlands)

Ashley, S.L.; Welton, A.R.; Harwood, K.M.; Rooijen, van N.; Spindler, K.R.

2009-01-01

Mouse adenovirus type 1 (MAV-1) causes acute and persistent infections in mice, with high levels of virus found in the brain, spinal cord and spleen in acute infections. MAV-1 infects endothelial cells throughout the mouse, and monocytes/macrophages have also been implicated as targets of the virus.

Role of blood ribosomal protein S19 in coagulum resorption: a study using Gln137Glu-ribosomal protein S19 gene knock-in mouse.

Science.gov (United States)

Chen, Jun; Fujino, Rika; Zhao, Rui; Semba, Umeko; Araki, Kimi; Yamamoto, Tetsuro

2014-11-01

Sera of human, guinea pig or mouse contain a strong monocyte chemoattractant capacity that is attributed to the ribosomal protein S19 (RP S19) oligomers generated during blood coagulation. In contrast, sera prepared from Gln137Glu-RP S19 gene knock-in mice contained negligible chemoattractant capacity. When coagula that had been pre-formed from the blood of both the wild type and knock-in mice were intraperitoneally inserted into host mice, after 3 days of recovery, the knock-in mouse coagula remained larger than the wild type mouse coagula. The wild type mouse coagula were covered by multiple macrophage layers at the surface and were infiltrated inside by macrophages. Knock-in mouse coagula exhibited less macrophage involvement. When coagula of knock-in mice and coagula of knock-in mice containing C5a/RP S19, an artificial substitute of the RP S19 oligomers, were intraperitoneally inserted as pairs, the C5a/RP S19 containing coagulum was more rapidly absorbed, concomitant with increased macrophage involvement. Finally, when the knock-in mouse and wild type mouse coagula pairs were inserted into mice in which macrophages had been depleted using clodronate liposome, the size difference of recovered coagula was reversed. These results indicate the importance of the RP S19 oligomer-induced macrophage recruitment in coagulum resorption. © 2014 Japanese Society of Pathology and Wiley Publishing Asia Pty Ltd.

Cranial mononeuropathy VI

Science.gov (United States)

... Abducens palsy; Lateral rectus palsy; VIth nerve palsy; Cranial nerve VI palsy; Sixth nerve palsy; Neuropathy - sixth nerve ... Cranial mononeuropathy VI is damage to the sixth cranial nerve. This nerve is also called the abducens nerve. ...

The slaty mutation affects the morphology and maturation of melanosomes in the mouse melanocytes.

Science.gov (United States)

Hirobe, Tomohisa; Abe, Hiroyuki

2006-10-01

The slaty (Dct(slt)) mutation is known to reduce the activity of dopachrome tautomerase in melanocytes and to reduce the melanin content in skin, hairs and eyes. Although the melanosomes in slaty melanocytes are reported to be eumelanosome-like, detailed melanosome biogenesis is not well studied. To address this point, melanosomes in neonatal epidermal melanocytes from wild-type (Dct+/Dct+) mice at the slaty locus as well as its congenic mouse mutant (Dct(slt)/Dct(slt)) in serum-free primary culture were observed under the electron microscope. Wild-type melanocytes possessed exclusively elliptical melanosomes with internal longitudinal structures, whereas in mutant melanocytes, numerous spherical melanosomes with globular depositions of pigment and elliptical melanosomes as well as mixed type of the two melanosomes were observed. Mature stage IV melanosomes were greatly decreased in mutant melanocytes, whereas immature stage III melanosomes were more numerous than in wild-type melanocytes. These results suggest that the slaty mutation affects the morphology and maturation of melanosomes in mouse melanocytes.

Gene therapy restores auditory and vestibular function in a mouse model of Usher syndrome type 1c.

Science.gov (United States)

Pan, Bifeng; Askew, Charles; Galvin, Alice; Heman-Ackah, Selena; Asai, Yukako; Indzhykulian, Artur A; Jodelka, Francine M; Hastings, Michelle L; Lentz, Jennifer J; Vandenberghe, Luk H; Holt, Jeffrey R; Géléoc, Gwenaëlle S

2017-03-01

Because there are currently no biological treatments for hearing loss, we sought to advance gene therapy approaches to treat genetic deafness. We focused on Usher syndrome, a devastating genetic disorder that causes blindness, balance disorders and profound deafness, and studied a knock-in mouse model, Ush1c c.216G>A, for Usher syndrome type IC (USH1C). As restoration of complex auditory and balance function is likely to require gene delivery systems that target auditory and vestibular sensory cells with high efficiency, we delivered wild-type Ush1c into the inner ear of Ush1c c.216G>A mice using a synthetic adeno-associated viral vector, Anc80L65, shown to transduce 80-90% of sensory hair cells. We demonstrate recovery of gene and protein expression, restoration of sensory cell function, rescue of complex auditory function and recovery of hearing and balance behavior to near wild-type levels. The data represent unprecedented recovery of inner ear function and suggest that biological therapies to treat deafness may be suitable for translation to humans with genetic inner ear disorders.

A mild mutator phenotype arises in a mouse model for malignancies associated with neurofibromatosis type 1

International Nuclear Information System (INIS)

Garza, Rene; Hudson, Robert A.; McMahan, C. Alex; Walter, Christi A.; Vogel, Kristine S.

2007-01-01

Defects in genes that control DNA repair, proliferation, and apoptosis can increase genomic instability, and thus promote malignant progression. Although most tumors that arise in humans with neurofibromatosis type 1 (NF1) are benign, these individuals are at increased risk for malignant peripheral nerve sheath tumors (MPNST). To characterize additional mutations required for the development of MPNST from benign plexiform neurofibromas, we generated a mouse model for these tumors by combining targeted null mutations in Nf1 and p53, in cis. CisNf1+/-; p53+/- mice spontaneously develop PNST, and these tumors exhibit loss-of-heterozygosity at both the Nf1 and p53 loci. Because p53 has well-characterized roles in the DNA damage response, DNA repair, and apoptosis, and because DNA repair genes have been proposed to act as modifiers in NF1, we used the cisNf1+/-; p53+/- mice to determine whether a mutator phenotype arises in NF1-associated malignancies. To quantitate spontaneous mutant frequencies (MF), we crossed the Big Blue mouse, which harbors a lacI transgene, to the cisNf1+/-; p53+/- mice, and isolated genomic DNA from both tumor and normal tissues in compound heterozygotes and wild-type siblings. Many of the PNST exhibited increased mutant frequencies (MF = 4.70) when compared to normal peripheral nerve and brain (MF = 2.09); mutations occurred throughout the entire lacI gene, and included base substitutions, insertions, and deletions. Moreover, the brains, spleens, and livers of these cisNf1+/-; p53+/- animals exhibited increased mutant frequencies when compared to tissues from wild-type littermates. We conclude that a mild mutator phenotype arises in the tumors and tissues of cisNf1+/-; p53+/- mice, and propose that genomic instability influences NF1 tumor progression and disease severity

Microvascular Cranial Nerve Palsy

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... Español Eye Health / Eye Health A-Z Microvascular Cranial Nerve Palsy Sections What Is Microvascular Cranial Nerve Palsy? ... Microvascular Cranial Nerve Palsy Treatment What Is Microvascular Cranial Nerve Palsy? Leer en Español: ¿Qué es una parálisis ...

Lower cranial nerves.

Science.gov (United States)

Soldatos, Theodoros; Batra, Kiran; Blitz, Ari M; Chhabra, Avneesh

2014-02-01

Imaging evaluation of cranial neuropathies requires thorough knowledge of the anatomic, physiologic, and pathologic features of the cranial nerves, as well as detailed clinical information, which is necessary for tailoring the examinations, locating the abnormalities, and interpreting the imaging findings. This article provides clinical, anatomic, and radiological information on lower (7th to 12th) cranial nerves, along with high-resolution magnetic resonance images as a guide for optimal imaging technique, so as to improve the diagnosis of cranial neuropathy. Copyright © 2014 Elsevier Inc. All rights reserved.

Effects of ketoconazole on the biodistribution and metabolism of [{sup 11}C]loperamide and [{sup 11}C]N-desmethyl-loperamide in wild-type and P-gp knockout mice

Energy Technology Data Exchange (ETDEWEB)

Seneca, Nicholas; Zoghbi, Sami S.; Shetty, H. Umesha; Tuan, Edward; Kannan, Pavitra; Taku, Andrew; Innis, Robert B. [Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892 (United States); Pike, Victor W. [Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892 (United States)], E-mail: pikev@mail.nih.gov

2010-04-15

Introduction: [{sup 11}C]Loperamide and [{sup 11}C]N-desmethyl-loperamide ([{sup 11}C]dLop) have been proposed as radiotracers for imaging brain P-glycoprotein (P-gp) function. A major route of [{sup 11}C]loperamide metabolism is N-demethylation to [{sup 11}C]dLop. We aimed to test whether inhibition of CYP3A4 with ketoconazole might reduce the metabolism of [{sup 11}C]loperamide and [{sup 11}C]dLop in mice, and thereby improve the quality of these radiotracers. Methods: Studies were performed in wild-type and P-gp knockout (mdr-1a/b -/-) mice. During each of seven study sessions, one pair of mice, comprising one wild-type and one knockout mouse, was pretreated with ketoconazole (50 mg/kg, ip), while another such pair was left untreated. Mice were sacrificed at 30 min after injection of [{sup 11}C]loperamide or [{sup 11}C]dLop. Whole brain and plasma samples were measured for radioactivity and analyzed with radio-high-performance liquid chromatography. Results: Ketoconazole increased the plasma concentrations of [{sup 11}C]loperamide and its main radiometabolite, [{sup 11}C]dLop, by about twofold in both wild-type and knockout mice, whereas the most polar radiometabolite was decreased threefold. Furthermore, ketoconazole increased the brain concentrations of [{sup 11}C]loperamide and the radiometabolite [{sup 11}C]dLop by about twofold in knockout mice, and decreased the brain concentrations of the major and most polar radiometabolite in wild-type and knockout mice by 82% and 49%, respectively. In contrast, ketoconazole had no effect on plasma and brain distribution of administered [{sup 11}C]dLop and its radiometabolites in either wild-type or knockout mice, except to increase the low plasma [{sup 11}C]dLop concentration. The least polar radiometabolite of [{sup 11}C]dLop was identified with LC-MS{sup n} as the N-hydroxymethyl analog of [{sup 11}C]dLop and this also behaved as a P-gp substrate. Conclusion: In this study, ketoconazole (50 mg/kg, ip) proved

Activation Of Wild-Type Hras Suppresses The Earliest Stages Of Pancreatic Cancer

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Jamie Weyandt

2015-08-01

Conclusions: Loss of wild-type Hras promotes the earliest stages of pancreatic tumorigenesis, and moreover results in more rapid progression of the disease. As such, mechanisms leading to activation of wild-type Ras proteins, including but not limited to redox-dependent reactions, may influence the development of pancreatic cancer.

Use of tissue-specific microRNA to control pathology of wild-type adenovirus without attenuation of its ability to kill cancer cells.

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Cawood, Ryan; Chen, Hannah H; Carroll, Fionnadh; Bazan-Peregrino, Miriam; van Rooijen, Nico; Seymour, Leonard W

2009-05-01

Replicating viruses have broad applications in biomedicine, notably in cancer virotherapy and in the design of attenuated vaccines; however, uncontrolled virus replication in vulnerable tissues can give pathology and often restricts the use of potent strains. Increased knowledge of tissue-selective microRNA expression now affords the possibility of engineering replicating viruses that are attenuated at the RNA level in sites of potential pathology, but retain wild-type replication activity at sites not expressing the relevant microRNA. To assess the usefulness of this approach for the DNA virus adenovirus, we have engineered a hepatocyte-safe wild-type adenovirus 5 (Ad5), which normally mediates significant toxicity and is potentially lethal in mice. To do this, we have included binding sites for hepatocyte-selective microRNA mir-122 within the 3' UTR of the E1A transcription cassette. Imaging versions of these viruses, produced by fusing E1A with luciferase, showed that inclusion of mir-122 binding sites caused up to 80-fold decreased hepatic expression of E1A following intravenous delivery to mice. Animals administered a ten-times lethal dose of wild-type Ad5 (5x10(10) viral particles/mouse) showed substantial hepatic genome replication and extensive liver pathology, while inclusion of 4 microRNA binding sites decreased replication 50-fold and virtually abrogated liver toxicity. This modified wild-type virus retained full activity within cancer cells and provided a potent, liver-safe oncolytic virus. In addition to providing many potent new viruses for cancer virotherapy, microRNA control of virus replication should provide a new strategy for designing safe attenuated vaccines applied across a broad range of viral diseases.

Phenobarbital induces cell cycle transcriptional responses in mouse liver humanized for constitutive androstane and pregnane x receptors.

Science.gov (United States)

Luisier, Raphaëlle; Lempiäinen, Harri; Scherbichler, Nina; Braeuning, Albert; Geissler, Miriam; Dubost, Valerie; Müller, Arne; Scheer, Nico; Chibout, Salah-Dine; Hara, Hisanori; Picard, Frank; Theil, Diethilde; Couttet, Philippe; Vitobello, Antonio; Grenet, Olivier; Grasl-Kraupp, Bettina; Ellinger-Ziegelbauer, Heidrun; Thomson, John P; Meehan, Richard R; Elcombe, Clifford R; Henderson, Colin J; Wolf, C Roland; Schwarz, Michael; Moulin, Pierre; Terranova, Rémi; Moggs, Jonathan G

2014-06-01

The constitutive androstane receptor (CAR) and the pregnane X receptor (PXR) are closely related nuclear receptors involved in drug metabolism and play important roles in the mechanism of phenobarbital (PB)-induced rodent nongenotoxic hepatocarcinogenesis. Here, we have used a humanized CAR/PXR mouse model to examine potential species differences in receptor-dependent mechanisms underlying liver tissue molecular responses to PB. Early and late transcriptomic responses to sustained PB exposure were investigated in liver tissue from double knock-out CAR and PXR (CAR(KO)-PXR(KO)), double humanized CAR and PXR (CAR(h)-PXR(h)), and wild-type C57BL/6 mice. Wild-type and CAR(h)-PXR(h) mouse livers exhibited temporally and quantitatively similar transcriptional responses during 91 days of PB exposure including the sustained induction of the xenobiotic response gene Cyp2b10, the Wnt signaling inhibitor Wisp1, and noncoding RNA biomarkers from the Dlk1-Dio3 locus. Transient induction of DNA replication (Hells, Mcm6, and Esco2) and mitotic genes (Ccnb2, Cdc20, and Cdk1) and the proliferation-related nuclear antigen Mki67 were observed with peak expression occurring between 1 and 7 days PB exposure. All these transcriptional responses were absent in CAR(KO)-PXR(KO) mouse livers and largely reversible in wild-type and CAR(h)-PXR(h) mouse livers following 91 days of PB exposure and a subsequent 4-week recovery period. Furthermore, PB-mediated upregulation of the noncoding RNA Meg3, which has recently been associated with cellular pluripotency, exhibited a similar dose response and perivenous hepatocyte-specific localization in both wild-type and CAR(h)-PXR(h) mice. Thus, mouse livers coexpressing human CAR and PXR support both the xenobiotic metabolizing and the proliferative transcriptional responses following exposure to PB.

Wild-type and A315T mutant TDP-43 exert differential neurotoxicity in a Drosophila model of ALS

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Estes, Patricia S.; Boehringer, Ashley; Zwick, Rebecca; Tang, Jonathan E.; Grigsby, Brianna; Zarnescu, Daniela C.

2011-01-01

The RNA-binding protein TDP-43 has been linked to amyotrophic lateral sclerosis (ALS) both as a causative locus and as a marker of pathology. With several missense mutations being identified within TDP-43, efforts have been directed towards generating animal models of ALS in mouse, zebrafish, Drosophila and worms. Previous loss of function and overexpression studies have shown that alterations in TDP-43 dosage recapitulate hallmark features of ALS pathology, including neuronal loss and locomotor dysfunction. Here we report a direct in vivo comparison between wild-type and A315T mutant TDP-43 overexpression in Drosophila neurons. We found that when expressed at comparable levels, wild-type TDP-43 exerts more severe effects on neuromuscular junction architecture, viability and motor neuron loss compared with the A315T allele. A subset of these differences can be compensated by higher levels of A315T expression, indicating a direct correlation between dosage and neurotoxic phenotypes. Interestingly, larval locomotion is the sole parameter that is more affected by the A315T allele than wild-type TDP-43. RNA interference and genetic interaction experiments indicate that TDP-43 overexpression mimics a loss-of-function phenotype and suggest a dominant-negative effect. Furthermore, we show that neuronal apoptosis does not require the cytoplasmic localization of TDP-43 and that its neurotoxicity is modulated by the proteasome, the HSP70 chaperone and the apoptosis pathway. Taken together, our findings provide novel insights into the phenotypic consequences of the A315T TDP-43 missense mutation and suggest that studies of individual mutations are critical for elucidating the molecular mechanisms of ALS and related neurodegenerative disorders. PMID:21441568

The effects of tissue-non-specific alkaline phosphatase gene therapy on craniosynostosis and craniofacial morphology in the FGFR2C342Y/+ mouse model of Crouzon craniosynostosis.

Science.gov (United States)

Wang, E; Nam, H K; Liu, J; Hatch, N E

2015-04-01

Craniosynostosis, the premature fusion of cranial bones, has traditionally been described as a disease of increased bone mineralization. However, multiple mouse models of craniosynostosis display craniosynostosis simultaneously with diminished cranial bone volume and/or density. We propose an alternative hypothesis that craniosynostosis results from abnormal tissue mineralization through the downregulation of tissue-non-specific alkaline phosphatase (TNAP) enzyme downstream of activating mutations in FGFRs. Neonatal Crouzon (FGFRC342Y/+) and wild-type (FGFR+/+) mice were injected with lentivirus to deliver a recombinant form of TNAP. Mice were sacrificed at 4 weeks postnatal. Serum was collected to test for alkaline phosphatase (AP), phosphorus, and calcium levels. Craniofacial bone fusion and morphology were assessed by micro-computed tomography. Injection with the TNAP lentivirus significantly increased serum AP levels (increased serum AP levels are indicative of efficient transduction and production of the recombinant protein), but results were variable and dependent upon viral lot and the litter of mice injected. Morphological analysis revealed craniofacial form differences for inferior surface (p=0.023) and cranial height (p=0.014) regions between TNAP lentivirus-injected and vehicle-injected Crouzon mice. With each unit increase in AP level, the odds of lambdoid suture fusion decreased by 84.2% and these results came close to statistical significance (p=0.068). These results suggest that TNAP deficiency may mediate FGFR2-associated craniosynostosis. Future studies should incorporate injection of recombinant TNAP protein, to avoid potential side effects and variable efficacy of lentiviral gene delivery. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Diagnosis and treatment of trigeminal schwannomas extending into both the middle and posterior cranial fossa

Institute of Scientific and Technical Information of China (English)

徐启武; 车晓明; 胡杰; 杨伯捷

2004-01-01

@@ Trigeminal schwannomas (TSs) account for 0.1%-0.4% of all intracranial tumors and 1%-8% of intracranial schwannomas.1,2 Yoshida and Kawase3 classified TSs into 6 types according to their locations: M (TS involving the middle cranial fossa), P (TS involving the posterior cranial fossa), E (TS located at extracranial space), MP (TS involving both the middle and the posterior cranial fossa), ME (TS involving the middle cranial fossa and the extracranial space), and MPE (TS involving the the middle and the posterior cranial fossa and the extracranial space). Of these types, MP is the commonest, but is difficult to be totally removed. Between January 1984 and June 2003, we surgically treated 28 patients with TSs of type MP and obtained satisfactory results. To make a correct diagnosis of TS, to select appropriate surgical approach, and to improve surgical outcome of TS of type MP, we analysed the related clinical data and experiences.

Potential Therapeutic Use of Relaxin in Healing Cranial Bone Defects

Science.gov (United States)

2017-09-01

to measure circulating concentrations of relaxin during the infusion by ELISA ; 3. sacrifice the mice at 10-12 days after cranial defect; 4. fix the...osmotic pump for 10-12 days, and to measure circulating concentrations of relaxin during the infusion by ELISA . Values of 0.35, 0.69, 1.61, 0.66, 1.99...vehicle-infused mice, because in our previous work, none was detected. This makes sense, because the ELISA we use does not detect mouse relaxin

Action potentials and ion conductances in wild-type and CALHM1-knockout type II taste cells

Science.gov (United States)

Saung, Wint Thu; Foskett, J. Kevin

2017-01-01

Taste bud type II cells fire action potentials in response to tastants, triggering nonvesicular ATP release to gustatory neurons via voltage-gated CALHM1-associated ion channels. Whereas CALHM1 regulates mouse cortical neuron excitability, its roles in regulating type II cell excitability are unknown. In this study, we compared membrane conductances and action potentials in single identified TRPM5-GFP-expressing circumvallate papillae type II cells acutely isolated from wild-type (WT) and Calhm1 knockout (KO) mice. The activation kinetics of large voltage-gated outward currents were accelerated in cells from Calhm1 KO mice, and their associated nonselective tail currents, previously shown to be highly correlated with ATP release, were completely absent in Calhm1 KO cells, suggesting that CALHM1 contributes to all of these currents. Calhm1 deletion did not significantly alter resting membrane potential or input resistance, the amplitudes and kinetics of Na+ currents either estimated from action potentials or recorded from steady-state voltage pulses, or action potential threshold, overshoot peak, afterhyperpolarization, and firing frequency. However, Calhm1 deletion reduced the half-widths of action potentials and accelerated the deactivation kinetics of transient outward currents, suggesting that the CALHM1-associated conductance becomes activated during the repolarization phase of action potentials. NEW & NOTEWORTHY CALHM1 is an essential ion channel component of the ATP neurotransmitter release mechanism in type II taste bud cells. Its contribution to type II cell resting membrane properties and excitability is unknown. Nonselective voltage-gated currents, previously associated with ATP release, were absent in cells lacking CALHM1. Calhm1 deletion was without effects on resting membrane properties or voltage-gated Na+ and K+ channels but contributed modestly to the kinetics of action potentials. PMID:28202574

Male-like sexual behavior of female mouse lacking fucose mutarotase

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Lim Dae-sik

2010-07-01

Full Text Available Abstract Background Mutarotases are recently characterized family of enzymes that are involved in the anomeric conversions of monosaccharides. The mammalian fucose mutarotase (FucM was reported in cultured cells to facilitate fucose utilization and incorporation into protein by glycosylation. However, the role of this enzyme in animal has not been elucidated. Results We generated a mutant mouse specifically lacking the fucose mutarotase (FucM gene. The FucM knockout mice displayed an abnormal sexual receptivity with a drastic reduction in lordosis score, although the animals were fertile due to a rare and forced intromission by a typical male. We examined the anteroventral periventricular nucleus (AVPv of the preoptic region in brain and found that the mutant females showed a reduction in tyrosine hydoxylase positive neurons compared to that of a normal female. Furthermore, the mutant females exhibited a masculine behavior, such as mounting to a normal female partner as well as showing a preference to female urine. We found a reduction of fucosylated serum alpha-fetoprotein (AFP in a mutant embryo relative to that of a wild-type embryo. Conclusions The observation that FucM-/- female mouse exhibits a phenotypic similarity to a wild-type male in terms of its sexual behavior appears to be due to the neurodevelopmental changes in preoptic area of mutant brain resembling a wild-type male. Since the previous studies indicate that AFP plays a role in titrating estradiol that are required to consolidate sexual preference of female mice, we speculate that the reduced level of AFP in FucM-/- mouse, presumably resulting from the reduced fucosylation, is responsible for the male-like sexual behavior observed in the FucM knock-out mouse.

Micro-evolutionary divergence patterns of mandible shapes in wild house mouse (Mus musculus populations

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Tautz Diethard

2011-10-01

Full Text Available Abstract Background Insights into the micro-evolutionary patterns of morphological traits require an assessment of the natural variation of the trait within and between populations and closely related species. The mouse mandible is a particularly suitable morphological trait for such an analysis, since it has long been used as a model to study the quantitative genetics of shape. In addition, many distinct populations, sub-species and closely related species are known for the house mouse. However, morphological comparisons among wild caught animals require an assessment in how far environmental and technical factors could interfere with the shape change measurements. Results Using geometric morphometrics, we have surveyed mandible shapes in 15 natural populations of the genus Mus, with a focus on the subspecies Mus musculus domesticus. In parallel we have carefully assessed possibly confounding technical and biological factors. We find that there are distinct differences on average between populations, subspecies and species, but these differences are smaller than differences between individuals within populations. Populations from summer-dry regions, although more ancestral, are less distinct from each other than are populations from the more recently colonized northern areas. Populations with especially distinct shapes occur in an area of sympatry of M. m. domesticus and M. spretus and on recently colonized sub-antarctic islands. We have also studied a number of inbred strains to assess in how far their mandible shapes resemble those from the wild. We find that they fall indeed into the shape space of natural variation between individuals in populations. Conclusions Although mandible shapes in natural populations can be influenced by environmental variables, these influences are insufficient to explain the average extent of shape differences between populations, such that evolutionary processes must be invoked to explain this level of diversity

Role of blink reflex in diagnosis of subclinical cranial neuropathy in diabetic mellitus type II.

Science.gov (United States)

Kazem, Shakouri S; Behzad, Davoudi

2006-05-01

Peripheral neuropathy (PN) is one of the late complications of diabetes mellitus. Cranial nerves III, VII, and V are among the most commonly affected in diabetic patients. Traditional electrodiagnosis (Edx) studies are a useful method for diagnosis of PN and symptomatic cranial neuropathy, and may not be useful for detecting subclinical involvement of cranial nerves. The main objective of this study is to evaluate the role of blink reflex (BR) for early diagnosis of cranial neuropathy in diabetic patients with PN. A prospective study was performed on NIDDM patients with PN. One hundred eighty-eight subjects were included in our study in which 142 acted as healthy subjects and 46 as diabetic patients. Patients were excluded with prior history of cranial nerve lesions, stroke, or any other disease with polyneuropathy or drug-induced neuropathy. Routine nerve conduction studies were performed, and only patients with PN were included in this study. Abnormalities were found in 54.4% of patients. R1, IR2, and CR2 were prolonged relative to the healthy group. Statistically there was no significant difference in R/D ratio of patients (P=0.201). Also, there was a positive correlation between R1, IR2, and CR2 latencies with duration of diabetes and severity of polyneuropathy, but not for R/D. The greatest correlation was shown in R1 latency (69.9% abnormality). BR is a noninvasive and very useful method for the evaluation and diagnosis of subclinical cranial nerve involvement in diabetic patients.

An unusual case of isolated sixth cranial nerve palsy in leprosy.

Science.gov (United States)

Vaishampayan, Sanjeev; Borde, Priyanka

2012-08-15

Cranial nerve involvement is not common in leprosy. The fifth and seventh cranial nerves are the most commonly affected in leprosy. Herein we present a patient with Hansen disease (BL) with type I reaction who developed isolated involvement of the sixth cranial nerve leading to lateral rectus muscle palsy. He responded to timely anti-reactional therapy and it produced a good response. Careful observation of patients with lepra reaction is needed to avoid damage to important organs.

Classification of Porcine Cranial Fracture Patterns Using a Fracture Printing Interface,.

Science.gov (United States)

Wei, Feng; Bucak, Serhat Selçuk; Vollner, Jennifer M; Fenton, Todd W; Jain, Anil K; Haut, Roger C

2017-01-01

Distinguishing between accidental and abusive head trauma in children can be difficult, as there is a lack of baseline data for pediatric cranial fracture patterns. A porcine head model has recently been developed and utilized in a series of studies to investigate the effects of impact energy level, surface type, and constraint condition on cranial fracture patterns. In the current study, an automated pattern recognition method, or a fracture printing interface (FPI), was developed to classify cranial fracture patterns that were associated with different impact scenarios documented in previous experiments. The FPI accurately predicted the energy level when the impact surface type was rigid. Additionally, the FPI was exceedingly successful in determining fractures caused by skulls being dropped with a high-level energy (97% accuracy). The FPI, currently developed on the porcine data, may in the future be transformed to the task of cranial fracture pattern classification for human infant skulls. © 2016 American Academy of Forensic Sciences.

No Effect of NGAL/lipocalin-2 on Aggressiveness of Cancer in the MMTV-PyMT/FVB/N Mouse Model for Breast Cancer

DEFF Research Database (Denmark)

Cramer, Elisabeth P; Glenthøj, Andreas; Häger, Mattias

2012-01-01

tumor volume, or to the number of metastases. Histology and gelatinolytic activity of the mammary tumors did not differ between wild-type and lipocalin-2-deficient mice. We conclude that NGAL/lipocalin-2 does not invariably affect the aggressiveness of breast cancers as assessed in mouse models, thus......NGAL/lipocalin-2 is a siderophore-binding protein that is highly expressed in several cancers. It is suggested to confer a proliferative advantage to cancer cells. Its expression has been correlated with aggressiveness of breast cancer as determined both in patients and in mouse breast cancer...... models. This was recently confirmed in two mouse models of spontaneous breast cancer in wild-type and lipocalin-2-deficient mice. We used a similar strategy using a different mouse strain. Lipocalin-2-deficient mice and mouse mammary tumor virus-polyoma middle T antigen (MMTV-PyMT) mice were crossed...

Comparative behaviour of lab.-cultured and wild-type Dacus oleae flies in the field

International Nuclear Information System (INIS)

Prokopy, R.J.; Haniotakis, G.E.; Economopoulos, A.P.

1975-01-01

Under field conditions, the authors compared the responses of lab.-type (ca. 85 generations under artificial conditions) and wild-type Dacus oleae flies to host plant colour and odour, host fruit colour and shape, small rectangles of different colours and shades, and McPhail-type traps of different colours baited with different odours. Except for the lab.-type flies being relatively more attracted toward red fruit models and small red rectangles and relatively less attracted toward yellow fruit models and small yellow rectangles than the wild type, the qualitative nature of the responses of the two fly types toward the various experimental treatments was essentially the same. Quantitatively, however, consistently smaller percentages of the released lab.-type than the released wild-type flies were recaptured, suggesting that the mobility, flight pattern, or vigour of the two types of flies may be different. (author)

Structure and Composition of Protein Bodies from Wild-Type and High-Lysine Barley Endosperm

DEFF Research Database (Denmark)

Ingversen, J.

1975-01-01

Protein bodies were isolated from 13 and 28 day old endosperms of barley mutant 1508 and its wild type, Bomi barley. The fine structure of the isolated protein bodies was determined by electron microscopy, and the proteins present in the preparations characterized by amino-acid analysis and SDS......-polyacrylamidegel electrophoresis. Sections through pellets of isolated protein bodies from both the mutant and the wild type revealed protein body structures corresponding with those observed in sections through the intact starchy endosperms. The majority of the wild-type protein bodies was homogeneous spheres accompanied...... that the wild-type protein bodies contained large amounts of prolamines (the storage protein group which is soluble in 55 % isopropanol) and some glutelins (the storage proteins soluble in dilute alkali), whereas the mutant protein bodies have glutelin as the major component and little prolamines...

Imaging of Cranial Nerves III, IV, VI in Congenital Cranial Dysinnervation Disorders.

Science.gov (United States)

Kim, Jae Hyoung; Hwang, Jeong Min

2017-06-01

Congenital cranial dysinnervation disorders are a group of diseases caused by abnormal development of cranial nerve nuclei or their axonal connections, resulting in aberrant innervation of the ocular and facial musculature. Its diagnosis could be facilitated by the development of high resolution thin-section magnetic resonance imaging. The purpose of this review is to describe the method to visualize cranial nerves III, IV, and VI and to present the imaging findings of congenital cranial dysinnervation disorders including congenital oculomotor nerve palsy, congenital trochlear nerve palsy, Duane retraction syndrome, Möbius syndrome, congenital fibrosis of the extraocular muscles, synergistic divergence, and synergistic convergence. © 2017 The Korean Ophthalmological Society.

Aerobic Glycolysis in the Frontal Cortex Correlates with Memory Performance in Wild-Type Mice But Not the APP/PS1 Mouse Model of Cerebral Amyloidosis.

Science.gov (United States)

Harris, Richard A; Tindale, Lauren; Lone, Asad; Singh, Olivia; Macauley, Shannon L; Stanley, Molly; Holtzman, David M; Bartha, Robert; Cumming, Robert C

2016-02-10

we detected an age-dependent decline in the expression of aerobic glycolysis enzymes and a concomitant decrease in lactate levels within the frontal cortex of wild-type mice. Improved memory performance in wild-type mice correlated with elevated expression of aerobic glycolysis enzymes. Surprisingly, lactate levels remained elevated with age and increased aerobic glycolysis enzyme expression correlated with poorer memory performance in APP/PS1 mice. These findings suggest that while lactate production is beneficial for memory in the healthy aging brain, it might be detrimental in an Alzheimer's disease context. Copyright © 2016 the authors 0270-6474/16/361871-08$15.00/0.

The action of the masticatory muscles and cranial changes in pigs as results of domestication

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Alexandru Dinu

2009-12-01

Full Text Available The comparative study of wild boar and domestic pig skulls suggests that a change in feeding habits under human control may have been a factor influencing the action of the masticatory and neck muscles in reshaping the cranial region. This paper offers both an anatomical and an osteological comparative morphological argument supporting this hypothesis.

Hypothalamic neurosecretory and circadian vasopressinergic neuronal systems in the blind cone-rod homeobox knock out mouse (Crx(-/-) ) and the 129sv wild type mouse

DEFF Research Database (Denmark)

Rovsing, Louise; Rath, Martin Fredensborg; Møller, Morten

2013-01-01

circadian AVP-rhythm. We have in this study of the brown 129sv mouse and the visual blind cone-rod homeobox gene knock out mouse (Crx(-/-) ) with degeneration of the retinal rods and cones, but a preserved non-image forming optic system, studied the temporal Avp-expression in both the neurosecretory...

Hes1 is required for appropriate morphogenesis and differentiation during mouse thyroid gland development.

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Aurore Carre

Full Text Available Notch signalling plays an important role in endocrine development, through its target gene Hes1. Hes1, a bHLH transcriptional repressor, influences progenitor cell proliferation and differentiation. Recently, Hes1 was shown to be expressed in the thyroid and regulate expression of the sodium iodide symporter (Nis. To investigate the role of Hes1 for thyroid development, we studied thyroid morphology and function in mice lacking Hes1. During normal mouse thyroid development, Hes1 was detected from E9.5 onwards in the median anlage, and at E11.5 in the ultimobranchial bodies. Hes1(-/- mouse embryos had a significantly lower number of Nkx2-1-positive progenitor cells (p<0.05 at E9.5 and at E11.5. Moreover, Hes1(-/- mouse embryos showed a significantly smaller total thyroid surface area (-40 to -60% compared to wild type mice at all study time points (E9.5-E16.5. In both Hes1(-/- and wild type mouse embryos, most Nkx2-1-positive thyroid cells expressed the cell cycle inhibitor p57 at E9.5 in correlation with low proliferation index. In Hes1(-/- mouse embryos, fusion of the median anlage with the ultimobranchial bodies was delayed by 3 days (E16.5 vs. E13.5 in wild type mice. After fusion of thyroid anlages, hypoplastic Hes1(-/- thyroids revealed a significantly decreased labelling area for T4 (-78% and calcitonin (-65% normalized to Nkx2-1 positive cells. Decreased T4-synthesis might be due to reduced Nis labelling area (-69%. These findings suggest a dual role of Hes1 during thyroid development: first, control of the number of both thyrocyte and C-cell progenitors, via a p57-independent mechanism; second, adequate differentiation and endocrine function of thyrocytes and C-cells.

[Cranial trepanation in primitive cultures].

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González-Darder, José Manuel

A review is presented on cranial trepanations performed by primitive cultures. The scientific interest in this topic began after the discovery in 1965 by Ephraim G. Squier of a pre-Columbian trepanated skull, and studied by Paul Broca in Paris. Pseudotrepanation and other types of cranial manipulation are reviewed. The techniques, technology, and instruments for every type of trepanation are well known. There are a surprisingly high percentage of cases showing signs of post-trepanation survival. Indications for trepanation are speculative, perhaps magic. Although trepanation in primitive cultures is widespread around the world, and throughout time, the main fields of interest are the Neolithic Period in Europe, the pre-Columbian Period in Andean South America, and some contemporaneous Pacific and African tribes. This particular trepanation procedure has no relationship with modern Neurosurgery, or with trepanations with therapeutic purposes performed since the Greco-Roman period in Europe, and afterwards around the world. Copyright © 2016 Sociedad Española de Neurocirugía. Publicado por Elsevier España, S.L.U. All rights reserved.

Expression of Caytaxin protein in Cayman Ataxia mouse models correlates with phenotype severity.

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Kristine M Sikora

Full Text Available Caytaxin is a highly-conserved protein, which is encoded by the Atcay/ATCAY gene. Mutations in Atcay/ATCAY have been identified as causative of cerebellar disorders such as the rare hereditary disease Cayman ataxia in humans, generalized dystonia in the dystonic (dt rat, and marked motor defects in three ataxic mouse lines. While several lines of evidence suggest that Caytaxin plays a critical role in maintaining nervous system processes, the physiological function of Caytaxin has not been fully characterized. In the study presented here, we generated novel specific monoclonal antibodies against full-length Caytaxin to examine endogenous Caytaxin expression in wild type and Atcay mutant mouse lines. Caytaxin protein is absent from brain tissues in the two severely ataxic Atcay(jit (jittery and Atcay(swd (sidewinder mutant lines, and markedly decreased in the mildly ataxic/dystonic Atcay(ji-hes (hesitant line, indicating a correlation between Caytaxin expression and disease severity. As the expression of wild type human Caytaxin in mutant sidewinder and jittery mice rescues the ataxic phenotype, Caytaxin's physiological function appears to be conserved between the human and mouse orthologs. Across multiple species and in several neuronal cell lines Caytaxin is expressed as several protein isoforms, the two largest of which are caused by the usage of conserved methionine translation start sites. The work described in this manuscript presents an initial characterization of the Caytaxin protein and its expression in wild type and several mutant mouse models. Utilizing these animal models of human Cayman Ataxia will now allow an in-depth analysis to elucidate Caytaxin's role in maintaining normal neuronal function.

[Study of the immunological mechanism of anti-tumor effects of 5-FU by establishing EL4 tumor-bearing mouse models].

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Li, Mo-Lin; Li, Chuan-Gang; Shu, Xiao-Hong; Li, Ming-Xia; Jia, Yu-Jie; Qin, Zhi-Hai

2007-11-01

To investigate the immunological mechanism of anti-tumor effect of 5-FU by establishing lymphoma EL4 tumor-bearing mouse models in wild type C57BL/6 mice and nude C57BL/6 mice, respectively. The mouse lymphoma EL4 cells were inoculated subcutaneously into wild type C57BL/6 mice (immune-competent mice). Twelve days later, 5-FU of different doses was administered intraperitoneally to treat these wild type C57BL/6 tumor-bearing mice. The size of tumors in the wild type C57BL/6 mice was observed and recorded to explore the minimal dose of 5-FU that could cure the tumor-bearing mice. Then the same amount of EL4 tumor cells was inoculated subcutaneously into wild type C57BL/6 mice and nude C57BL/6 mice (T cell-deficient mice) simultaneously, which had the same genetic background of C57BL/6. Twelve days later, 5-FU of the minimal dose was given intraperitoneally to treat both the wild type and nude C57BL/6 tumor-bearing mice. The size of tumors in the two different types of mice was observed and recorded. A single dose of 5-FU (75 mg/kg) cured both the EL4 tumor-bearing wild type C57BL/6 mice and the EL4 tumor-bearing nude C57BL/6 mice in the first week. Two weeks after 5-FU treatment, all of the nude mice died of tumor relapse while most of the wild type C57BL/6 mice were fully recovered. A single dose of 5-FU has marked anti-tumor effects on lymphoma EL4 tumor-bearing C57BL/6 mice with or without T lymphocytes. The relapse of tumors after 5-FU treatment might be related to the function of T lymphocytes.

Cranial and dental analysis of mouse-like hamsters of the genus Calomyscus (Rodentia: Calomyscidae) from plateau of Iran

OpenAIRE

Shahabi, Saeed; Darvish, Jamshid; Aliabadian, Mansour; Mirshamsi, Omid; Mohammadi, Zeinolabedien

2012-01-01

To assess morphometric interspecific differences, we studied by multivariate and univariate analyses 32 cranial, mandibular and dental variables and four standard external measurements in 84 specimens of the genus Calomyscus (C. elburzensis, C. bailwardi, C. hotsoni and C. grandis) from Iran. Almost all mean cranial measurements in C. grandis were larger than in the other three species, while the opposite occurred for C. hotsoni. C. bailwardi showed the smallest dental measurement. Principal ...

Expression of the type VI intermediate filament proteins CP49 and filensin in the mouse lens epithelium.

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FitzGerald, Paul; Sun, Ning; Shibata, Brad; Hess, John F

2016-01-01

The differentiated lens fiber cell assembles a filamentous cytoskeletal structure referred to as the beaded filament (BF). The BF requires CP49 (bfsp2) and filensin (bfsp1) for assembly, both of which are highly divergent members of the large intermediate filament (IF) family of proteins. Thus far, these two proteins have been reported only in the differentiated lens fiber cell. For this reason, both proteins have been considered robust markers of fiber cell differentiation. We report here that both proteins are also expressed in the mouse lens epithelium, but only after 5 weeks of age. Localization of CP49 was achieved with immunocytochemical probing of wild-type, CP49 knockout, filensin knockout, and vimentin knockout mice, in sections and in the explanted lens epithelium, at the light microscope and electron microscope levels. The relationship between CP49 and other cytoskeletal elements was probed using fluorescent phalloidin, as well as with antibodies to vimentin, GFAP, and α-tubulin. The relationship between CP49 and the aggresome was probed with antibodies to γ-tubulin, ubiquitin, and HDAC6. CP49 and filensin were expressed in the mouse lens epithelium, but only after 5 weeks of age. At the light microscope level, these two proteins colocalize to a large tubular structure, approximately 7 × 1 μm, which was typically present at one to two copies per cell. This structure is found in the anterior and anterolateral lens epithelium, including the zone where mitosis occurs. The structure becomes smaller and largely undetectable closer to the equator where the cell exits the cell cycle and commits to fiber cell differentiation. This structure bears some resemblance to the aggresome and is reactive with antibodies to HDAC6, a marker for the aggresome. However, the structure does not colocalize with antibodies to γ-tubulin or ubiquitin, also markers for the aggresome. The structure also colocalizes with actin but appears to largely exclude vimentin and �

Pathological Roles of Wild-Type Cu, Zn-Superoxide Dismutase in Amyotrophic Lateral Sclerosis

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Yoshiaki Furukawa

2012-01-01

Full Text Available Dominant mutations in a Cu, Zn-superoxide dismutase (SOD1 gene cause a familial form of amyotrophic lateral sclerosis (ALS. While it remains controversial how SOD1 mutations lead to onset and progression of the disease, many in vitro and in vivo studies have supported a gain-of-toxicity mechanism where pathogenic mutations contribute to destabilizing a native structure of SOD1 and thus facilitate misfolding and aggregation. Indeed, abnormal accumulation of SOD1-positive inclusions in spinal motor neurons is a pathological hallmark in SOD1-related familial ALS. Furthermore, similarities in clinical phenotypes and neuropathology of ALS cases with and without mutations in sod1 gene have implied a disease mechanism involving SOD1 common to all ALS cases. Although pathogenic roles of wild-type SOD1 in sporadic ALS remain controversial, recent developments of novel SOD1 antibodies have made it possible to characterize wild-type SOD1 under pathological conditions of ALS. Here, I have briefly reviewed recent progress on biochemical and immunohistochemical characterization of wild-type SOD1 in sporadic ALS cases and discussed possible involvement of wild-type SOD1 in a pathomechanism of ALS.

A STUDY OF TUMOURS OF THE CRANIAL NERVE AND PARASPINAL NERVE

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Sudesh Shetty

2016-03-01

Full Text Available INTRODUCTION One of the frequent sites of tumour formation is the cranial nerves and paraspinal nerves. The cranial nerves perform a plethora of functions and so the signs and symptoms caused may be different. They are mainly classified into four different types. The aim of the study is: 1. To study the tumours arising from the cranial nerves in an epidemiological point of view. 2. To study the tumours histopathologically. 3. To classify the tumours according to WHO classification. Thirty-eight brain tumor cases were studied in the Department of Medicine, A. J. Shetty Institute of Medical Sciences, Mangalore. Cranial nerve tumours accounts for 4(10% among the intracranial tumours. Schwannomas makes up 3(7.39% among the Intracranial tumours. and constituted 3(75% among cranial nerve tumours. All the 3 schwannomas were located in CP angle. The geographic distribution of cases was found to be 28 cases from Mangalore and 10 cases from Kerala.

A Ten-Week Biochemistry Lab Project Studying Wild-Type and Mutant Bacterial Alkaline Phosphatase

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Witherow, D. Scott

2016-01-01

This work describes a 10-week laboratory project studying wild-type and mutant bacterial alkaline phosphatase, in which students purify, quantitate, and perform kinetic assays on wild-type and selected mutants of the enzyme. Students also perform plasmid DNA purification, digestion, and gel analysis. In addition to simply learning important…

Differential induction of Toll-like receptors & type 1 interferons by Sabin attenuated & wild type 1 polioviruses in human neuronal cells.

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Mohanty, Madhu C; Deshpande, Jagadish M

2013-01-01

Polioviruses are the causative agent of paralytic poliomyelitis. Attenuated polioviruses (Sabin oral poliovirus vaccine strains) do not replicate efficiently in neurons as compared to the wild type polioviruses and therefore do not cause disease. This study was aimed to investigate the differential host immune response to wild type 1 poliovirus (wild PV) and Sabin attenuated type 1 poliovirus (Sabin PV) in cultured human neuronal cells. By using flow cytometry and real time PCR methods we examined host innate immune responses and compared the role of toll like receptors (TLRs) and cytoplasmic RNA helicases in cultured human neuronal cells (SK-N-SH) infected with Sabin PV and wild PV. Human neuronal cells expressed very low levels of TLRs constitutively. Sabin PV infection induced significantly higher expression of TLR3, TLR7 and melanoma differentiation-associated protein-5 (MDA-5) m-RNA in neuronal cells at the beginning of infection (up to 4 h) as compared to wild PV. Further, Sabin PV also induced the expression of interferon α/β at early time point of infection. The induced expression of IFN α/β gene by Sabin PV in neuronal cells could be suppressed by inhibiting TLR7. Neuronal cell innate immune response to Sabin and wild polioviruses differ significantly for TLR3, TLR7, MDA5 and type 1 interferons. Effects of TLR7 activation and interferon production and Sabin virus replication in neuronal cells need to be actively investigated in future studies.

Tracking by flow cytometry antigen-specific follicular helper T cells in wild-type animals after protein vaccination.

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Chakarov, Svetoslav; Fazilleau, Nicolas

2015-01-01

Flow cytometry is a valuable technology used in immunology to characterize and enumerate the different cell subpopulations specific for a nonself-antigen in the context of an ongoing immune response. Among them, follicular helper T cells are the cognate regulators of B cells in secondary lymphoid tissues. Thus, tracking them is of high interest especially in the context of protein vaccination. For this purpose, transgenic antigen-receptor mouse models have been largely used. It is now clear that transgenic models are not always the best means to study the dynamics of the immune response since they can modify the response. In this chapter, we describe how to track endogenous antigen-specific follicular helper T cells by flow cytometry after protein vaccination in nonmodified wild-type animals, which ultimately provides a comprehensive way to enumerate, characterize, and isolate these particular cells in vivo.

Effect of sclerostin antibody treatment in a mouse model of severe osteogenesis imperfecta.

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Roschger, Andreas; Roschger, Paul; Keplingter, Petra; Klaushofer, Klaus; Abdullah, Sami; Kneissel, Michaela; Rauch, Frank

2014-09-01

Osteogenesis imperfecta (OI) is a heritable bone fragility disorder that is usually caused by mutations affecting collagen type I production in osteoblasts. Stimulation of bone formation through sclerostin antibody treatment (Sost-ab) has shown promising results in mouse models of relatively mild OI. We assessed the effect of once-weekly intravenous Sost-ab injections for 4weeks in male Col1a1(Jrt)/+mice, a model of severe dominant OI, starting either at 4weeks (growing mice) or at 20weeks (adult mice) of age. Sost-ab had no effect on weight or femur length. In OI mice, no significant treatment-associated differences in serum markers of bone formation (alkaline phosphatase activity, procollagen type I N-propeptide) or resorption (C-telopeptide of collagen type I) were found. Micro-CT analyses at the femur showed that Sost-ab treatment was associated with higher trabecular bone volume and higher cortical thickness in wild type mice at both ages and in growing OI mice, but not in adult OI mice. Three-point bending tests of the femur showed that in wild type but not in OI mice, Sost-ab was associated with higher ultimate load and work to failure. Quantitative backscattered electron imaging of the femur did not show any effect of Sost-ab on CaPeak (the most frequently occurring calcium concentration in the bone mineral density distribution), regardless of genotype, age or measurement location. Thus, Sost-ab had a larger effect in wild type than in Col1a1(Jrt)/+mice. Previous studies had found marked improvements of Sost-ab on bone mass and strength in an OI mouse model with a milder phenotype. Our data therefore suggest that Sost-ab is less effective in a more severely affected OI mouse model. Copyright © 2014 Elsevier Inc. All rights reserved.

FGF9 can induce endochondral ossification in cranial mesenchyme

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Overbeek Paul A

2006-02-01

Full Text Available Abstract Background The flat bones of the skull (i.e., the frontal and parietal bones normally form through intramembranous ossification. At these sites cranial mesenchymal cells directly differentiate into osteoblasts without the formation of a cartilage intermediate. This type of ossification is distinct from endochondral ossification, a process that involves initial formation of cartilage and later replacement by bone. Results We have analyzed a line of transgenic mice that expresses FGF9, a member of the fibroblast growth factor family (FGF, in cranial mesenchymal cells. The parietal bones in these mice show a switch from intramembranous to endochondral ossification. Cranial cartilage precursors are induced to proliferate, then hypertrophy and are later replaced by bone. These changes are accompanied by upregulation of Sox9, Ihh, Col2a1, Col10a1 and downregulation of CbfaI and Osteocalcin. Fate mapping studies show that the cranial mesenchymal cells in the parietal region that show a switch in cell fate are likely to be derived from the mesoderm. Conclusion These results demonstrate that FGF9 expression is sufficient to convert the differentiation program of (at least a subset of mesoderm-derived cranial mesenchyme cells from intramembranous to endochondral ossification.

Chronic cranial window with access port for repeated cellular manipulations, drug application, and electrophysiology

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Christopher Joel Roome

2014-11-01

Full Text Available Chronic cranial windows have been instrumental in advancing optical studies in vivo, permitting long-term, high-resolution imaging in various brain regions. However, once a window is attached it is difficult to regain access to the brain under the window for cellular manipulations. Here we describe a simple device that combines long term in vivo optical imaging with direct brain access via glass or quartz pipettes and metal, glass, or quartz electrodes for cellular manipulations like dye or drug injections and electrophysiological stimulations or recordings while keeping the craniotomy sterile. Our device comprises a regular cranial window glass coverslip with a drilled access hole later sealed with biocompatible silicone. This chronic cranial window with access port is cheap, easy to manufacture, can be mounted just as the regular chronic cranial window, and is self-sealing after retraction of the pipette or electrode. We demonstrate that multiple injections can be performed through the silicone port by repetitively bolus loading calcium sensitive dye into mouse barrel cortex and recording spontaneous cellular activity over a period of weeks. As an example to the extent of its utility for electrophysiological recording, we describe how simple removal of the silicone seal can permit patch pipette access for whole-cell patch clamp recordings in vivo. During these chronic experiments we do not observe any infections under the window or impairment of animal health.

Differential induction of Toll-like receptors & type 1 interferons by Sabin attenuated & wild type 1 polioviruses in human neuronal cells

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Madhu C Mohanty

2013-01-01

Full Text Available Background & objectives: Polioviruses are the causative agent of paralytic poliomyelitis. Attenuated polioviruses (Sabin oral poliovirus vaccine strains do not replicate efficiently in neurons as compared to the wild type polioviruses and therefore do not cause disease. This study was aimed to investigate the differential host immune response to wild type 1 poliovirus (wild PV and Sabin attenuated type 1 poliovirus (Sabin PV in cultured human neuronal cells. Methods: By using flow cytometry and real time PCR methods we examined host innate immune responses and compared the role of toll like receptors (TLRs and cytoplasmic RNA helicases in cultured human neuronal cells (SK-N-SH infected with Sabin PV and wild PV. Results: Human neuronal cells expressed very low levels of TLRs constitutively. Sabin PV infection induced significantly higher expression of TLR3, TLR7 and melanoma differentiation-associated protein-5 (MDA-5 m-RNA in neuronal cells at the beginning of infection (up to 4 h as compared to wild PV. Further, Sabin PV also induced the expression of interferon α/β at early time point of infection. The induced expression of IFN α/β gene by Sabin PV in neuronal cells could be suppressed by inhibiting TLR7. Interpretation & conclusions: Neuronal cell innate immune response to Sabin and wild polioviruses differ significantly for TLR3, TLR7, MDA5 and type 1 interferons. Effects of TLR7 activation and interferon production and Sabin virus replication in neuronal cells need to be actively investigated in future studies.

The Cranial Nerve Skywalk: A 3D Tutorial of Cranial Nerves in a Virtual Platform

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Richardson-Hatcher, April; Hazzard, Matthew; Ramirez-Yanez, German

2014-01-01

Visualization of the complex courses of the cranial nerves by students in the health-related professions is challenging through either diagrams in books or plastic models in the gross laboratory. Furthermore, dissection of the cranial nerves in the gross laboratory is an extremely meticulous task. Teaching and learning the cranial nerve pathways…

Reduced type II interleukin-4 receptor signalling drives initiation, but not progression, of colorectal carcinogenesis: evidence from transgenic mouse models and human case?control epidemiological observations

OpenAIRE

Ingram, Nicola; Northwood, Emma L.; Perry, Sarah L.; Marston, Gemma; Snowden, Helen; Taylor, John C.; Scott, Nigel; Bishop, D. Timothy; Coletta, P. Louise; Hull, Mark A.

2013-01-01

We investigated the role of interleukin (IL)-4 receptor (IL-4R) signalling during mouse carcinogen-induced colorectal carcinogenesis and in a case-control genetic epidemiological study of IL-4Rα single nucleotide polymorphisms (SNPs). Azoxymethane-induced aberrant crypt focus (ACF; 6 weeks) and tumours (32 weeks) were analysed in wild-type (WT) BALB/c mice, as well as in IL-4Rα (-) (/-) , IL-13 (-/-) and 'double-knockout' (DKO) animals. Colorectal cancer (CRC) cases (1502) and controls (584) ...

Pharmacologic Treatment Assigned for Niemann Pick Type C1 Disease Partly Changes Behavioral Traits in Wild-Type Mice.

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Schlegel, Victoria; Thieme, Markus; Holzmann, Carsten; Witt, Martin; Grittner, Ulrike; Rolfs, Arndt; Wree, Andreas

2016-11-09

Niemann-Pick Type C1 (NPC1) is an autosomal recessive inherited disorder characterized by accumulation of cholesterol and glycosphingolipids. Previously, we demonstrated that BALB/c-npc1 nih Npc1 -/- mice treated with miglustat, cyclodextrin and allopregnanolone generally performed better than untreated Npc1 -/- animals. Unexpectedly, they also seemed to accomplish motor tests better than their sham-treated wild-type littermates. However, combination-treated mutant mice displayed worse cognition performance compared to sham-treated ones. To evaluate effects of these drugs in healthy BALB/c mice, we here analyzed pharmacologic effects on motor and cognitive behavior of wild-type mice. For combination treatment mice were injected with allopregnanolone/cyclodextrin weekly, starting at P7. Miglustat injections were performed daily from P10 till P23. Starting at P23, miglustat was embedded in the chow. Other mice were treated with miglustat only, or sham-treated. The battery of behavioral tests consisted of accelerod, Morris water maze, elevated plus maze, open field and hot-plate tests. Motor capabilities and spontaneous motor behavior were unaltered in both drug-treated groups. Miglustat-treated wild-type mice displayed impaired spatial learning compared to sham- and combination-treated mice. Both combination- and miglustat-treated mice showed enhanced anxiety in the elevated plus maze compared to sham-treated mice. Additionally, combination treatment as well as miglustat alone significantly reduced brain weight, whereas only combination treatment reduced body weight significantly. Our results suggest that allopregnanolone/cyclodextrin ameliorate most side effects of miglustat in wild-type mice.

Pharmacologic Treatment Assigned for Niemann Pick Type C1 Disease Partly Changes Behavioral Traits in Wild-Type Mice

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Victoria Schlegel

2016-11-01

Full Text Available Niemann-Pick Type C1 (NPC1 is an autosomal recessive inherited disorder characterized by accumulation of cholesterol and glycosphingolipids. Previously, we demonstrated that BALB/c-npc1nihNpc1−/− mice treated with miglustat, cyclodextrin and allopregnanolone generally performed better than untreated Npc1−/− animals. Unexpectedly, they also seemed to accomplish motor tests better than their sham-treated wild-type littermates. However, combination-treated mutant mice displayed worse cognition performance compared to sham-treated ones. To evaluate effects of these drugs in healthy BALB/c mice, we here analyzed pharmacologic effects on motor and cognitive behavior of wild-type mice. For combination treatment mice were injected with allopregnanolone/cyclodextrin weekly, starting at P7. Miglustat injections were performed daily from P10 till P23. Starting at P23, miglustat was embedded in the chow. Other mice were treated with miglustat only, or sham-treated. The battery of behavioral tests consisted of accelerod, Morris water maze, elevated plus maze, open field and hot-plate tests. Motor capabilities and spontaneous motor behavior were unaltered in both drug-treated groups. Miglustat-treated wild-type mice displayed impaired spatial learning compared to sham- and combination-treated mice. Both combination- and miglustat-treated mice showed enhanced anxiety in the elevated plus maze compared to sham-treated mice. Additionally, combination treatment as well as miglustat alone significantly reduced brain weight, whereas only combination treatment reduced body weight significantly. Our results suggest that allopregnanolone/cyclodextrin ameliorate most side effects of miglustat in wild-type mice.

Normal cranial CT anatomy

International Nuclear Information System (INIS)

Gado, M.H.; Rao, K.C.V.G.

1987-01-01

The human brain consists of well-known anatomical components. Some parts of these components have been shown to be concerned with certain functions. A complete cranial CT examination consists of a series of several slices obtained in a sequence usually from the base to the vertex of the cranial vault, in the axial mode. The ultimate goal of this chapter is to pinpoint those slices that depict a given anatomical structure or several structures that deal with a given function. To achieve this goal, the discussion of CT cranial anatomy is presented in three sections

Intraoperative cranial nerve monitoring.

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Harper, C Michel

2004-03-01

The purpose of intraoperative monitoring is to preserve function and prevent injury to the nervous system at a time when clinical examination is not possible. Cranial nerves are delicate structures and are susceptible to damage by mechanical trauma or ischemia during intracranial and extracranial surgery. A number of reliable electrodiagnostic techniques, including nerve conduction studies, electromyography, and the recording of evoked potentials have been adapted to the study of cranial nerve function during surgery. A growing body of evidence supports the utility of intraoperative monitoring of cranial nerve nerves during selected surgical procedures.

Transcervical Inoculation with Chlamydia trachomatis Induces Infertility in HLA-DR4 Transgenic and Wild-Type Mice.

Science.gov (United States)

Pal, Sukumar; Tifrea, Delia F; Zhong, Guangming; de la Maza, Luis M

2018-01-01

Chlamydia trachomatis is the leading cause of infection-induced infertility in women. Attempts to control this epidemic with screening programs and antibiotic therapy have failed. Currently, a vaccine to prevent C. trachomatis infections is not available. In order to develop an animal model for evaluating vaccine antigens that can be applied to humans, we used C. trachomatis serovar D (strain UW-3/Cx) to induce infertility in mice whose major histocompatibility complex class II antigen was replaced with the human leukocyte antigen DR4 (HLA-DR4). Transcervical inoculation of medroxyprogesterone-treated HLA-DR4 transgenic mice with 5 × 10 5 C. trachomatis D inclusion forming units (IFU) induced a significant reduction in fertility, with a mean number of embryos/mouse of 4.4 ± 1.3 compared to 7.8 ± 0.5 for the uninfected control mice ( P < 0.05). A similar fertility reduction was elicited in the wild-type (WT) C57BL/6 mice (4.3 ± 1.4 embryos/mouse) compared to the levels of the WT controls (9.1 ± 0.4 embryos/mouse) ( P < 0.05). Following infection, WT mice mounted more robust humoral and cellular immune responses than HLA-DR4 mice. As determined by vaginal shedding, HLA-DR4 mice were more susceptible to a transcervical C. trachomatis D infection than WT mice. To assess if HLA-DR4 transgenic and WT mice could be protected by vaccination, 10 4 IFU of C. trachomatis D was delivered intranasally, and mice were challenged transcervically 6 weeks later with 5 × 10 5 IFU of C. trachomatis D. As determined by severity and length of vaginal shedding, WT C57BL/6 and HLA-DR4 mice were significantly protected by vaccination. The advantages and limitations of the HLA-DR4 transgenic mouse model for evaluating human C. trachomatis vaccine antigens are discussed. Copyright © 2017 American Society for Microbiology.

Wild type measles virus attenuation independent of type I IFN

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Horvat Branka

2008-02-01

Full Text Available Abstract Background Measles virus attenuation has been historically performed by adaptation to cell culture. The current dogma is that attenuated virus strains induce more type I IFN and are more resistant to IFN-induced protection than wild type (wt. Results The adaptation of a measles virus isolate (G954-PBL by 13 passages in Vero cells induced a strong attenuation of this strain in vivo. The adapted virus (G954-V13 differs from its parental strain by only 5 amino acids (4 in P/V/C and 1 in the M gene. While a vaccine strain, Edmonston Zagreb, could replicate equally well in various primate cells, both G954 strains exhibited restriction to the specific cell type used initially for their propagation. Surprisingly, we observed that both G954 strains induced type I IFN, the wt strain inducing even more than the attenuated ones, particularly in human plasmacytoid Dendritic Cells. Type I IFN-induced protection from the infection of both G954 strains depended on the cell type analyzed, being less efficient in the cells used to grow the viral strain. Conclusion Thus, mutations in M and P/V/C proteins can critically affect MV pathogenicity, cellular tropism and lead to virus attenuation without interfering with the α/β IFN system.

Normal cranial bone marrow MR imaging pattern with age-related ADC value distribution

International Nuclear Information System (INIS)

Li Qi; Pan Shinong; Yin Yuming; Li Wei; Chen Zhian; Liu Yunhui; Wu Zhenhua; Guo Qiyong

2011-01-01

Objective: To determine MRI appearances of normal age-related cranial bone marrow and the relationship between MRI patterns and apparent diffusion coefficient (ADC) values. Methods: Five hundred subjects were divided into seven groups based on ages. Cranial bone marrow MRI patterns were performed based on different thickness of the diploe and signal intensity distribution characteristics. ADC values of the frontal, parietal, occipital and temporal bones on DWI were measured and calculated. Correlations between ages and ADC values, between patterns and ADC values, as well as the distribution of ADC values were analyzed. Results: Normal cranial bone marrow was divided into four types and six subtypes, Type I, II, III and IV, which had positive correlation with age increasing (χ 2 = 266.36, P 0.05). In addition, there was significant negative correlation between the ADC values and MRI patterns in the normal parietal and occipital bones (r = -0.691 and -0.750, P < 0.01). Conclusion: The combination of MRI features and ADC values changes in different cranial bones showed significant correlation with age increasing. Familiar with the MRI appearance of the normal bone marrow conversion pattern in different age group and their ADC value will aid the diagnosis and differential of the cranial bone pathology.

Hes1 Is Required for Appropriate Morphogenesis and Differentiation during Mouse Thyroid Gland Development

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Carre, Aurore; Rachdi, Latif; Tron, Elodie; Richard, Bénédicte; Castanet, Mireille; Schlumberger, Martin; Bidart, Jean-Michel

2011-01-01

Notch signalling plays an important role in endocrine development, through its target gene Hes1. Hes1, a bHLH transcriptional repressor, influences progenitor cell proliferation and differentiation. Recently, Hes1 was shown to be expressed in the thyroid and regulate expression of the sodium iodide symporter (Nis). To investigate the role of Hes1 for thyroid development, we studied thyroid morphology and function in mice lacking Hes1. During normal mouse thyroid development, Hes1 was detected from E9.5 onwards in the median anlage, and at E11.5 in the ultimobranchial bodies. Hes1 −/− mouse embryos had a significantly lower number of Nkx2-1-positive progenitor cells (p<0.05) at E9.5 and at E11.5. Moreover, Hes1 −/− mouse embryos showed a significantly smaller total thyroid surface area (−40 to −60%) compared to wild type mice at all study time points (E9.5−E16.5). In both Hes1 −/− and wild type mouse embryos, most Nkx2-1-positive thyroid cells expressed the cell cycle inhibitor p57 at E9.5 in correlation with low proliferation index. In Hes1 −/− mouse embryos, fusion of the median anlage with the ultimobranchial bodies was delayed by 3 days (E16.5 vs. E13.5 in wild type mice). After fusion of thyroid anlages, hypoplastic Hes1 −/− thyroids revealed a significantly decreased labelling area for T4 (−78%) and calcitonin (−65%) normalized to Nkx2-1 positive cells. Decreased T4-synthesis might be due to reduced Nis labelling area (−69%). These findings suggest a dual role of Hes1 during thyroid development: first, control of the number of both thyrocyte and C-cell progenitors, via a p57-independent mechanism; second, adequate differentiation and endocrine function of thyrocytes and C-cells. PMID:21364918

Identification of concomitant infection with Chlamydia trachomatis IncA-negative mutant and wild-type strains by genomic, transcriptional, and biological characterizations.

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Suchland, Robert J; Jeffrey, Brendan M; Xia, Minsheng; Bhatia, Ajay; Chu, Hencelyn G; Rockey, Daniel D; Stamm, Walter E

2008-12-01

Clinical isolates of Chlamydia trachomatis that lack IncA on their inclusion membrane form nonfusogenic inclusions and have been associated with milder, subclinical infections in patients. The molecular events associated with the generation of IncA-negative strains and their roles in chlamydial sexually transmitted infections are not clear. We explored the biology of the IncA-negative strains by analyzing their genomic structure, transcription, and growth characteristics in vitro and in vivo in comparison with IncA-positive C. trachomatis strains. Three clinical samples were identified that contained a mixture of IncA-positive and -negative same-serovar C. trachomatis populations, and two more such pairs were found in serial isolates from persistently infected individuals. Genomic sequence analysis of individual strains from each of two serovar-matched pairs showed that these pairs were very similar genetically. In contrast, the genome sequence of an unmatched IncA-negative strain contained over 5,000 nucleotide polymorphisms relative to the genome sequence of a serovar-matched but otherwise unlinked strain. Transcriptional analysis, in vitro culture kinetics, and animal modeling demonstrated that IncA-negative strains isolated in the presence of a serovar-matched wild-type strain are phenotypically more similar to the wild-type strain than are IncA-negative strains isolated in the absence of a serovar-matched wild-type strain. These studies support a model suggesting that a change from an IncA-positive strain to the previously described IncA-negative phenotype may involve multiple steps, the first of which involves a translational inactivation of incA, associated with subsequent unidentified steps that lead to the observed decrease in transcript level, differences in growth rate, and differences in mouse infectivity.

Cranial Neuropathy in Multiple Sclerosis

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Mine Hayriye Sorgun

2011-09-01

Full Text Available OBJECTIVE: It has been reported that cranial neuropathy findings could be seen in the neurologic examination of multiple sclerosis (MS patients, although brain magnetic resonance imaging (MRI may not reveal any lesion responsible for the cranial nerve involvement. The aim of this study was to determine the frequency of brainstem and cranial nerve involvement, except for olfactory and optic nerves, during MS attacks, and to investigate the rate of an available explanation for the cranial neuropathy findings by lesion localization on brain MRI. METHODS: Ninety-five attacks of 86 MS patients were included in the study. The patients underwent a complete neurological examination, and cranial nerve palsies (CNP were determined during MS attacks. RESULTS: CNP were found as follows: 3rd CNP in 7 (7.4%, 4th CNP in 1 (1.1%, 5th CNP in 6 (6.3%, 6th CNP in 12 (12.6%, 7th CNP in 5 (5.3%, 8th CNP in 4 (4.2%, and 9th and 10th CNP in 2 (2.1% out of 95 attacks. Internuclear ophthalmoplegia (INO was detected in 5 (5.4%, nystagmus in 37 (38.9%, vertigo in 9 (6.3%, and diplopia in 14 (14.7% out of 95 attacks. Pons, mesencephalon and bulbus lesions were detected in 58.7%, 41.5% and 21.1% of the patients, respectively, on the brain MRI. Cranial nerve palsy findings could not be explained by the localization of the lesions on brainstem MRI in 5 attacks; 2 of them were 3rd CNP (1 with INO, 2 were 6th CNP and 1 was a combination of 6th, 7th and 8th CNP. CONCLUSION: The most frequently affected cranial nerve and brainstem region in MS patients is the 6th cranial nerve and pons, respectively. A few of the MS patients have normal brainstem MRI, although they have cranial neuropathy findings in the neurologic examination.

Development of teeth in chick embryos after mouse neural crest transplantations

OpenAIRE

Mitsiadis, Thimios A.; Chéraud, Yvonnick; Sharpe, Paul; Fontaine-Pérus, Josiane

2003-01-01

Teeth were lost in birds 70–80 million years ago. Current thinking holds that it is the avian cranial neural crest-derived mesenchyme that has lost odontogenic capacity, whereas the oral epithelium retains the signaling properties required to induce odontogenesis. To investigate the odontogenic capacity of ectomesenchyme, we have used neural tube transplantations from mice to chick embryos to replace the chick neural crest cell populations with mouse neural crest cells. The mouse/chick ...

Genetic relationships and epidemiological links between wild type 1 poliovirus isolates in Pakistan and Afghanistan.

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Angez, Mehar; Shaukat, Shahzad; Alam, Muhammad M; Sharif, Salmaan; Khurshid, Adnan; Zaidi, Syed Sohail Zahoor

2012-02-22

Efforts have been made to eliminate wild poliovirus transmission since 1988 when the World Health Organization began its global eradication campaign. Since then, the incidence of polio has decreased significantly. However, serotype 1 and serotype 3 still circulate endemically in Pakistan and Afghanistan. Both countries constitute a single epidemiologic block representing one of the three remaining major global reservoirs of poliovirus transmission. In this study we used genetic sequence data to investigate transmission links among viruses from diverse locations during 2005-2007. In order to find the origins and routes of wild type 1 poliovirus circulation, polioviruses were isolated from faecal samples of Acute Flaccid Paralysis (AFP) patients. We used viral cultures, two intratypic differentiation methods PCR, ELISA to characterize as vaccine or wild type 1 and nucleic acid sequencing of entire VP1 region of poliovirus genome to determine the genetic relatedness. One hundred eleven wild type 1 poliovirus isolates were subjected to nucleotide sequencing for genetic variation study. Considering the 15% divergence of the sequences from Sabin 1, Phylogenetic analysis by MEGA software revealed that active inter and intra country transmission of many genetically distinct strains of wild poliovirus type 1 belonged to genotype SOAS which is indigenous in this region. By grouping wild type 1 polioviruses according to nucleotide sequence homology, three distinct clusters A, B and C were obtained with multiple chains of transmission together with some silent circulations represented by orphan lineages. Our results emphasize that there was a persistent transmission of wild type 1 polioviruses in Pakistan and Afghanistan during 2005-2007. The epidemiologic information provided by the sequence data can contribute to the formulation of better strategies for poliomyelitis control to those critical areas, associated with high risk population groups which include migrants

Genetic relationships and epidemiological links between wild type 1 poliovirus isolates in Pakistan and Afghanistan

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Angez Mehar

2012-02-01

Full Text Available Abstract Background/Aim Efforts have been made to eliminate wild poliovirus transmission since 1988 when the World Health Organization began its global eradication campaign. Since then, the incidence of polio has decreased significantly. However, serotype 1 and serotype 3 still circulate endemically in Pakistan and Afghanistan. Both countries constitute a single epidemiologic block representing one of the three remaining major global reservoirs of poliovirus transmission. In this study we used genetic sequence data to investigate transmission links among viruses from diverse locations during 2005-2007. Methods In order to find the origins and routes of wild type 1 poliovirus circulation, polioviruses were isolated from faecal samples of Acute Flaccid Paralysis (AFP patients. We used viral cultures, two intratypic differentiation methods PCR, ELISA to characterize as vaccine or wild type 1 and nucleic acid sequencing of entire VP1 region of poliovirus genome to determine the genetic relatedness. Results One hundred eleven wild type 1 poliovirus isolates were subjected to nucleotide sequencing for genetic variation study. Considering the 15% divergence of the sequences from Sabin 1, Phylogenetic analysis by MEGA software revealed that active inter and intra country transmission of many genetically distinct strains of wild poliovirus type 1 belonged to genotype SOAS which is indigenous in this region. By grouping wild type 1 polioviruses according to nucleotide sequence homology, three distinct clusters A, B and C were obtained with multiple chains of transmission together with some silent circulations represented by orphan lineages. Conclusion Our results emphasize that there was a persistent transmission of wild type1 polioviruses in Pakistan and Afghanistan during 2005-2007. The epidemiologic information provided by the sequence data can contribute to the formulation of better strategies for poliomyelitis control to those critical areas

Cranial nerve palsies

International Nuclear Information System (INIS)

Ruggieri, P.; Adelizzi, J.; Modic, M.T.; Ross, J.S.; Tkach, J.; Masaryk, T.J.

1990-01-01

This paper evaluates the utility of multiplanar reconstructions (MPRs) of three-dimensional (3D) MR angiography data sets in the examination of patients with cranial nerve palsies. The authors hypothesis was that 3D data could be reformatted to highlight the intricate spatial relationships of vessels to adjacent neural tissues by taking advantage of the high vessel-parenchyma contrast in high-resolution 3D time-of-flight sequences. Twenty patients with cranial nerve palsies and 10 asymptomatic patients were examined with coronal T1-weighted and axial T2-weighted imaging plus a gadolinium-enhanced 3D MRA sequence (40/7/15 degrees, axial 60-mm volume, 0.9-mm isotropic resolution). Cranial nerves II-VIII were subsequently evaluated on axial and reformatted coronal and/or sagittal images

A neuroanatomical and physiological study of the non-image forming visual system of the cone-rod homeobox gene (Crx) knock out mouse

DEFF Research Database (Denmark)

Rovsing, Louise; Rath, Martin F; Lund-Andersen, Casper

2010-01-01

The anatomy and physiology of the non-image forming visual system was investigated in a visually blind cone-rod homeobox gene (Crx) knock-out mouse (Crx(-)(/)(-)), which lacks the outer segments of the photoreceptors. We show that the suprachiasmatic nuclei (SCN) in the Crx(-/-) mouse exhibit...... melanopsin neurons or the SCN may be necessary for a normal function of the non-image forming system of the mouse. However, a change in the SCN of the Crx(-/-) mouse might also explain the observed circadian differences between the knock out mouse and wild type mouse....

Neuromuscular ultrasound of cranial nerves.

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Tawfik, Eman A; Walker, Francis O; Cartwright, Michael S

2015-04-01

Ultrasound of cranial nerves is a novel subdomain of neuromuscular ultrasound (NMUS) which may provide additional value in the assessment of cranial nerves in different neuromuscular disorders. Whilst NMUS of peripheral nerves has been studied, NMUS of cranial nerves is considered in its initial stage of research, thus, there is a need to summarize the research results achieved to date. Detailed scanning protocols, which assist in mastery of the techniques, are briefly mentioned in the few reference textbooks available in the field. This review article focuses on ultrasound scanning techniques of the 4 accessible cranial nerves: optic, facial, vagus and spinal accessory nerves. The relevant literatures and potential future applications are discussed.

Rearing in seawater mesocosms improves the spawning performance of growth hormone transgenic and wild-type coho salmon.

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Rosalind A Leggatt

Full Text Available Growth hormone (GH transgenes can significantly accelerate growth rates in fish and cause associated alterations to their physiology and behaviour. Concern exists regarding potential environmental risks of GH transgenic fish, should they enter natural ecosystems. In particular, whether they can reproduce and generate viable offspring under natural conditions is poorly understood. In previous studies, GH transgenic salmon grown under contained culture conditions had lower spawning behaviour and reproductive success relative to wild-type fish reared in nature. However, wild-type salmon cultured in equal conditions also had limited reproductive success. As such, whether decreased reproductive success of GH transgenic salmon is due to the action of the transgene or to secondary effects of culture (or a combination has not been fully ascertained. Hence, salmon were reared in large (350,000 L, semi-natural, seawater tanks (termed mesocosms designed to minimize effects of standard laboratory culture conditions, and the reproductive success of wild-type and GH transgenic coho salmon from mesocosms were compared with that of wild-type fish from nature. Mesocosm rearing partially restored spawning behaviour and success of wild-type fish relative to culture rearing, but remained lower overall than those reared in nature. GH transgenic salmon reared in the mesocosm had similar spawning behaviour and success as wild-type fish reared in the mesocosm when in full competition and without competition, but had lower success in male-only competition experiments. There was evidence of genotype×environmental interactions on spawning success, so that spawning success of transgenic fish, should they escape to natural systems in early life, cannot be predicted with low uncertainty. Under the present conditions, we found no evidence to support enhanced mating capabilities of GH transgenic coho salmon compared to wild-type salmon. However, it is clear that GH transgenic

Cranial Suture Closure in Domestic Dog Breeds and Its Relationships to Skull Morphology.

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Geiger, Madeleine; Haussman, Sinah

2016-04-01

Bulldog-type brachycephalic domestic dog breeds are characterized by a relatively short and broad skull with a dorsally rotated rostrum (airorhynchy). Not much is known about the association between a bulldog-type skull conformation and peculiar patterns of suture and synchondrosis closure in domestic dogs. In this study, we aim to explore breed-specific patterns of cranial suture and synchondrosis closure in relation to the prebasial angle (proxy for airorhynchy and thus bulldog-type skull conformation) in domestic dogs. For this purpose, we coded closure of 18 sutures and synchondroses in 26 wolves, that is, the wild ancestor of all domestic dogs, and 134 domestic dogs comprising 11 breeds. Comparisons of the relative amount of closing and closed sutures and synchondroses (closure scores) in adult individuals showed that bulldog-type breeds have significantly higher closure scores than non-bulldog-type breeds and that domestic dogs have significantly higher closure scores than the wolf. We further found that the prebasial angle is significantly positively correlated with the amount of closure of the basispheno-presphenoid synchondrosis and sutures of the nose (premaxillo-nasal and maxillo-nasal) and the palate (premaxillo-maxillary and interpalatine). Our results show that there is a correlation between patterns of suture and synchondrosis closure and skull shape in domestic dogs, although the causal relationships remain elusive. © 2016 Wiley Periodicals, Inc.

Development of teeth in chick embryos after mouse neural crest transplantations.

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Mitsiadis, Thimios A; Chéraud, Yvonnick; Sharpe, Paul; Fontaine-Pérus, Josiane

2003-05-27

Teeth were lost in birds 70-80 million years ago. Current thinking holds that it is the avian cranial neural crest-derived mesenchyme that has lost odontogenic capacity, whereas the oral epithelium retains the signaling properties required to induce odontogenesis. To investigate the odontogenic capacity of ectomesenchyme, we have used neural tube transplantations from mice to chick embryos to replace the chick neural crest cell populations with mouse neural crest cells. The mouse/chick chimeras obtained show evidence of tooth formation showing that avian oral epithelium is able to induce a nonavian developmental program in mouse neural crest-derived mesenchymal cells.

The wild type as concept and in experimental practice: A history of its role in classical genetics and evolutionary theory.

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Holmes, Tarquin

2017-06-01

Wild types in genetics are specialised strains of laboratory experimental organism which principally serve as standards against which variation is measured. As selectively inbred lineages highly isolated from ancestral wild populations, there appears to be little wild or typical about them. I will nonetheless argue that they have historically been successfully used as stand-ins for nature, allowing knowledge produced in the laboratory to be extrapolated to the natural world. In this paper, I will explore the 19th century origins of the wild type concept, the theoretical and experimental innovations which allowed concepts and organisms to move from wild nature to laboratory domestication c. 1900 (resulting in the production of standardised lab strains), and the conflict among early geneticists between interactionist and atomist accounts of wild type, which would eventually lead to the conceptual disintegration of wild types and the triumph of genocentrism and population genetics. I conclude by discussing how the strategy of using wild type strains to represent nature in the lab has nonetheless survived the downfall of the wild type concept and continues to provide, significant limitations acknowledged, an epistemically productive means of investigating heredity and evolutionary variation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Fusarium spp. Associated with Field-Grown Grain of Near-Isogenic Low Lignin and Wild-Type Sorghum

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Fusarium spp. associated with field-grown grain of near-isogenic low lignin and wild-type sorghum. Deanna Funnell-Harris and Jeff Pedersen, USDA-ARS, Lincoln, NE Previous studies indicated that low lignin brown midrib (bmr) sorghum may be more resistant to Fusarium spp. than wild-type and that phen...

Transplacental and oral transmission of wild-type bluetongue virus serotype 8 in cattle after experimental infection

NARCIS (Netherlands)

Backx, A.; Heutink, C.G.; Rooij, van E.M.A.; Rijn, van P.A.

2009-01-01

Potential vertical transmission of wild-type bluetongue virus serotype 8 (BTV-8) in cattle was explored in this experiment. We demonstrated transplacental transmission of wild-type BTV-8 in one calf and oral infection with BTV-8 in another calf. Following the experimental BTV-8 infection of seven

CT measurements of cranial growth: microcephaly

International Nuclear Information System (INIS)

Hahn, F.J.; Chu, W.K.; Torkelson, R.D.

1984-01-01

Computed tomographic (CT) head scans were measured to determine the cranial dimensions of four children with microcephaly. These measurements were compared with cranial dimensions of normal children. CT proved to be useful in determining the developmental status of children with neurologic problems relative to their normal counterparts on the basis on cranial dimensions

Chinese herbal extract Su-duxing had potent inhibitory effects on both wild-type and entecavir-resistant hepatitis B virus (HBV) in vitro and effectively suppressed HBV replication in mouse model.

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Liu, Yan; Yao, Weiming; Si, Lanlan; Hou, Jun; Wang, Jiabo; Xu, Zhihui; Li, Weijie; Chen, Jianhong; Li, Ruisheng; Li, Penggao; Bo, Lvping; Xiao, Xiaohe; Lan, Jinchu; Xu, Dongping

2018-04-24

The present study aimed to investigate anti-HBV effect and major active compounds of Su-duxing, a medicine extracted from Chinese herbs. HBV-replicating cell lines HepG2.2.15 (wild-type) and HepG2. A64 (entecavir-resistant) were used for in vitro test. C57BL/6 mice infected by adeno-associated virus carrying 1.3 mer wild-type HBV genome were used for in vivo test. Inhibitory rates of Su-duxing (10 μg/mL) on HBV replicative intermediate and HBsAg levels were 75.1%, 51.0% in HepG2.2.15 cells and 65.2%, 42.9% in HepG2. A64 cells. The 50% inhibitory concentration of Su-duxing and entecavir on HBV replicative intermediates had 0.2-fold and 712.5-fold increase respectively for entecavir-resistant HBV compared to wild-type HBV. Mice treated with Su-duxing (45.0 mg kg -1  d -1 for 2 weeks) had 1.39 log 10 IU/mL decrease of serum HBV DNA, and 48.9% and 51.7% decrease of serum HBsAg and HBeAg levels. GeneChip and KEGG analysis proposed that anti-HBV mechanisms included relief of HBx stability and viral replication, deregulation of early cell cycle checkpoints, and induction of type I interferon. Six active compounds (Matrine, Oxymatrine, Chlorogenic acid, Sophocarpine, Baicalein, and Wogonin) against HBV were identified in Su-duxing. Greater anti-HBV effects were observed in some compound pairs compared to each single compound. In conclusion, Su-duxing had potent inhibitory effects on both wild-type and entecavir-resistant HBV. Its effects were associated with coordinated roles of active compounds in its composition. Copyright © 2018. Published by Elsevier B.V.

Mouse lysozyme-M knockout mice reveal how the self-determinant hierarchy shapes the T cell repertoire against this circulating self antigen in wild-type mice

NARCIS (Netherlands)

Sinha, Pratima; Chi, Howard H.; Kim, Hong R.; Clausen, Björn E.; Pederson, Brian; Sercarz, Eli E.; Forster, Irmgard; Moudgil, Kamal D.

2004-01-01

We have studied T cell tolerance to defined determinants within ML-M using wild-type (WT; ML-M+/+) and LysMcre (ML-M-/-) C3H (H-2(k)) mice to determine the relative contribution of ML-M-derived epitopes vs those from other self Ags in selection of the ML-M-specific T cell repertoire. ML-M was

Cranial nerves III, IV and VI

International Nuclear Information System (INIS)

Laine, I.J.; Smoker, W.R.; Kuta, A.J.; Felton, W.L.

1991-01-01

Because of advances in CT and MR imaging, accurate identification and evaluation of cranial nerve lesions is now possible. Cranial nerves III, IV, and VI, providing motor and sensory control of the eye, can be evaluated as a unit. In this paper, the authors present an overview of the anatomy and pathology of these cranial nerves. We first illustrate their normal anatomic pathways from the brain stem to the orbit. This is followed by clinical examples of patients with a variety of isolated and complex palsies of these three cranial nerves. This is accomplished by inclusion of ocular photographs, correlative imaging studies, and the use of diagrams. Knowledge of the gross and imaging anatomy and the ophthalmologic manifestations of pathology affecting these three cranial nerves permits a tailored approach to their evaluation

Age-related pattern of normal cranial bone marrow: MRI study

International Nuclear Information System (INIS)

Pan Shinong; Li Qi; Li Wei; Chen Zhian; Wu Zhenhua; Guo Qiyong; Liu Yunhui

2009-01-01

Objective: To investigate the age-related pattern of normal skull bone marrow with 3.0 T MR T 1 WI. Methods: Cranial MR T 1 WI images which were defined to be normal were retrospectively reviewed in 360 cases. Patients with known diffuse bone marrow disease, focal lesions, history of radiation treatment or steroid therapy were excluded, while patients whose cranial MRI and follow-up visits were all normal were included in this study. All the subjects were divided into 7 groups according to the age: 50 years group. Mid- and para- sagittal T 1 WI images were used to be analyzed and the type of cranial bone marrow was classified according to the thickness of diploe and the pattern of the signal characteristics. Statistical analysis was conducted to reveal the relationship between the age and the type. Results: The normal skull bone marrow could be divided into four types as follows: (1) Type-I: 115 cases, 47 of which appeared type- Ia and the mean thickness was (1.24±0.31) mm; 68 of which appeared type-Ib and the mean thickness was (1.76±0.37) mm. Type-II: 57 cases and the mean thickness was (2.78 ± 0.69) mm. Type-III: 148 cases, 18 of which appeared type-IIIa and the mean thickness was (2.33 ± 0.65) mm; 88 of which appeared type-IIIb and the mean thickness was (4.01± 0.86) mm; 42 of which appeared type-IIIc and the mean thickness was (4.31±0.73) mm. Type-IV: 40 cases, 25 of which appeared type-IVa and the mean thickness was (5.17±1.02) mm; 15 of which appeared type-IVb and the mean thickness was (5.85±1.45) mm. (2) 2 =266.36, P<0.01). Conclusion: There is characteristic in the distribution of normal skull bone marrow with age growing. And skull bone marrow transforms gradually from type-I to IV with aging. (authors)

PET imaging of brain with the β-amyloid probe, [11C]6-OH-BTA-1, in a transgenic mouse model of Alzheimer's disease

International Nuclear Information System (INIS)

Toyama, Hiroshi; Ye, Daniel; Cohen, Robert M.; Ichise, Masanori; Liow, Jeih-San; Cai, Lisheng; Musachio, John L.; Hong, Jinsoo; Crescenzo, Mathew; Tipre, Dnyanesh; Lu, Jian-Qiang; Zoghbi, Sami; Vines, Douglass C.; Pike, Victor W.; Innis, Robert B.; Jacobowitz, David; Seidel, Jurgen; Green, Michael V.; Katada, Kazuhiro

2005-01-01

The purpose of this study was to evaluate the capacity of [ 11 C]6-OH-BTA-1 and positron emission tomography (PET) to quantify β-amyloid (Aβ) plaques in the Tg2576 mouse model of Alzheimer's disease (AD). PET imaging was performed with the NIH ATLAS small animal scanner in six elderly transgenic mice (Tg2576; age 22.0±1.8 months; 23.6±2.6 g) overexpressing a mutated form of human β-amyloid precursor protein (APP) known to result in the production of Aβ plaques, and in six elderly wild-type litter mates (age 21.8±1.6 months; 29.5±4.7 g). Dynamic PET scans were performed for 30 min in each mouse under 1% isoflurane inhalation anesthesia after a bolus injection of 13-46 MBq of [ 11 C]6-OH-BTA-1. PET data were reconstructed with 3D OSEM. On the coronal PET image, irregular regions of interest (ROIs) were placed on frontal cortex (FR), parietal cortex (PA), striatum (ST), thalamus (TH), pons (PO), and cerebellum (CE), guided by a mouse stereotaxic atlas. Time-activity curves (TACs) (expressed as percent injected dose per gram normalized to body weight: % ID-kg/g) were obtained for FR, PA, ST, TH, PO, and CE. ROI-to-CE radioactivity ratios were also calculated. Following PET scans, sections of mouse brain prepared from anesthetized and fixative-perfused mice were stained with thioflavin-S. TACs for [ 11 C]6-OH-BTA-1 in all ROIs peaked early (at 30-55 s), with radioactivity washing out quickly thereafter in both transgenic and wild-type mice. Peak uptake in all regions was significantly lower in transgenic mice than in wild-type mice. During the later part of the washout phase (12-30 min), the mean FR/CE and PA/CE ratios were higher in transgenic than in wild-type mice (1.06±0.04 vs 0.98±0.07, p=0.04; 1.06±0.09 vs 0.93±0.08 p=0.02) while ST/CE, TH/CE, and PO/CE ratios were not. Ex vivo staining revealed widespread Aβ plaques in cortex, but not in cerebellum of transgenic mice or in any brain regions of wild-type mice. Marked reductions in brain uptake of this

On the mechanistic differences of benzene-induced leukemogenesis between wild type and p53 knockout mice

International Nuclear Information System (INIS)

Hirabayashi, Yoko; Yoon, Byung-Il; Kawasaki, Yasushi; Li, Guang-Xun; Kanno, Jun; Inoue, Tohru

2003-01-01

Leukemia induction by benzene inhalation was first reported by Le Noire in 1887, described multiple cases of leukemia among Parisian cobblers. However, experimental induction of leukemia by benzene exposure was not succeeded for a hundred years, until Snyder et al. and our group reported it nearly 20 years ago. Nevertheless, the mechanistic background of benzene-induced leukemia was still an enigma until recently a benzene-induced peculiar cell kinetics of the stem/progenitor cells has been elucidated by our study, demonstrated a marked repeated oscillatory decrease in peripheral blood and bone marrow (BM) cellularity during and after benzene exposure, which epigenetically preceded and developed the leukemia more than a year later. We utilized the BUUV (bromodeoxyuridine + UV exposure) method to study stem/progenitor cell kinetics during and/or after benzene exposure. Using these methods, we were able to measure the labeling rate, cycling fraction of clonogenic progenitor cells, and other cell cycle parameters. The cycling fraction of stem/progenitor cells was found not to turn into an active hematopoiesis but to remain low during benzene inhalation and further we found evidence that the cycling fraction depression may be mediated in part by a slowing of stem/progenitor cell cycling perse by up-regulation of p21. The benzene induced leukemogenicity between mice carrying wild-type p53 and mice lacking p53 seem to differ from one another. In the case of p53 knockout mouse, DNA damage such as weak mutagenicity and or chromosomal damages are retained, and those damages participated in the induction of a consequent activation of proto-oncogenes and the like, which led cells to further neoplastic changes. In contrast, in the case of wild type mice, a dramatic oscillational change in the cell cycle of the stem cell compartment seems to be an important factor for mice carrying the p53 gene. (author)

Modulation of ambient temperature promotes inflammation and initiates atherosclerosis in wild type C57BL/6 mice

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Daniel A. Giles

2016-11-01

Full Text Available Objectives: Obesity and obesity-associated inflammation is central to a variety of end-organ sequelae including atherosclerosis, a leading cause of death worldwide. Although mouse models have provided important insights into the immunopathogenesis of various diseases, modeling atherosclerosis in mice has proven difficult. Specifically, wild-type (WT mice are resistant to developing atherosclerosis, while commonly used genetically modified mouse models of atherosclerosis are poor mimics of human disease. The lack of a physiologically relevant experimental model of atherosclerosis has hindered the understanding of mechanisms regulating disease development and progression as well as the development of translational therapies. Recent evidence suggests that housing mice within their thermoneutral zone profoundly alters murine physiology, including both metabolic and immune processes. We hypothesized that thermoneutral housing would allow for augmentation of atherosclerosis induction and progression in mice. Methods: ApoE−/− and WT mice were housed at either standard (TS or thermoneutral (TN temperatures and fed either a chow or obesogenic “Western” diet. Analysis included quantification of (i obesity and obesity-associated downstream sequelae, (ii the development and progression of atherosclerosis, and (iii inflammatory gene expression pathways related to atherosclerosis. Results: Housing mice at TN, in combination with an obesogenic “Western” diet, profoundly augmented obesity development, exacerbated atherosclerosis in ApoE−/− mice, and initiated atherosclerosis development in WT mice. This increased disease burden was associated with altered lipid profiles, including cholesterol levels and fractions, and increased aortic plaque size. In addition to the mild induction of atherosclerosis, we similarly observed increased levels of aortic and white adipose tissue inflammation and increased circulating immune cell expression of pathways

Constitutively active Notch1 converts cranial neural crest-derived frontonasal mesenchyme to perivascular cells in vivo

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Sophie R. Miller

2017-03-01

Full Text Available Perivascular/mural cells originate from either the mesoderm or the cranial neural crest. Regardless of their origin, Notch signalling is necessary for their formation. Furthermore, in both chicken and mouse, constitutive Notch1 activation (via expression of the Notch1 intracellular domain is sufficient in vivo to convert trunk mesoderm-derived somite cells to perivascular cells, at the expense of skeletal muscle. In experiments originally designed to investigate the effect of premature Notch1 activation on the development of neural crest-derived olfactory ensheathing glial cells (OECs, we used in ovo electroporation to insert a tetracycline-inducible NotchΔE construct (encoding a constitutively active mutant of mouse Notch1 into the genome of chicken cranial neural crest cell precursors, and activated NotchΔE expression by doxycycline injection at embryonic day 4. NotchΔE-targeted cells formed perivascular cells within the frontonasal mesenchyme, and expressed a perivascular marker on the olfactory nerve. Hence, constitutively activating Notch1 is sufficient in vivo to drive not only somite cells, but also neural crest-derived frontonasal mesenchyme and perhaps developing OECs, to a perivascular cell fate. These results also highlight the plasticity of neural crest-derived mesenchyme and glia.

Augmentation of phenotype in a transgenic Parkinson mouse heterozygous for a Gaucher mutation.

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Fishbein, Ianai; Kuo, Yien-Ming; Giasson, Benoit I; Nussbaum, Robert L

2014-12-01

The involvement of the protein α-synuclein (SNCA) in the pathogenesis of Parkinson's disease is strongly supported by the facts that (i) missense and copy number mutations in the SNCA gene can cause inherited Parkinson's disease; and (ii) Lewy bodies in sporadic Parkinson's disease are largely composed of aggregated SNCA. Unaffected heterozygous carriers of Gaucher disease mutations have an increased risk for Parkinson's disease. As mutations in the GBA gene encoding glucocerebrosidase (GBA) are known to interfere with lysosomal protein degradation, GBA heterozygotes may demonstrate reduced lysosomal SNCA degradation, leading to increased steady-state SNCA levels and promoting its aggregation. We have created mouse models to investigate the interaction between GBA mutations and synucleinopathies. We investigated the rate of SNCA degradation in cultured primary cortical neurons from mice expressing wild-type mouse SNCA, wild-type human SNCA, or mutant A53T SNCA, in a background of either wild-type Gba or heterozygosity for the L444P GBA mutation associated with Gaucher disease. We also tested the effect of this Gaucher mutation on motor and enteric nervous system function in these transgenic animals. We found that human SNCA is stable, with a half-life of 61 h, and that the A53T mutation did not significantly affect its half-life. Heterozygosity for a naturally occurring Gaucher mutation, L444P, reduced GBA activity by 40%, reduced SNCA degradation and triggered accumulation of the protein in culture. This mutation also resulted in the exacerbation of motor and gastrointestinal deficits found in the A53T mouse model of Parkinson's disease. This study demonstrates that heterozygosity for a Gaucher disease-associated mutation in Gba interferes with SNCA degradation and contributes to its accumulation, and exacerbates the phenotype in a mouse model of Parkinson's disease. © The Author (2014). Published by Oxford University Press on behalf of the Guarantors of Brain

The effect of UVB on flavonoid biosynthesis in wild type and mutant petunia and arabidopsis

International Nuclear Information System (INIS)

Ryan, K.G.; Swinny, E.E.; Markham, K.R.; Winefield, C.

2000-01-01

Full text: Flavonoids may protect plants against damage by UVB radiation. Flavonoid composition and mRNA expression were determined following growth of plants under natural light, and under natural light with low UVB and with enhanced UVB. In wild-type Arabidopsis and Petunia, UVB induced an increase in total levels of flavonols and this was due to an up-regulation of, several genes coding for key enzymes in the phenylpropanoid pathway. In addition, UVB induced a higher rate of production of the di-hydroxylated si flavonol, quercetin glycoside than of the mono-hydroxylated equivalent, of kaempferol glycoside. Thus the ratio of quercetin to kaempferol increased with UVB treatment in wild type plants, and this suggests that the flavonoid r 3'hydroxylase (F3'H) enzyme, which converts dihydrokaempferol to dihydroquercetin, may play a key role in plant protection from UVB. Mutant plants of both species lacking this F3'H gene were grown under similar UV conditions. Leaves of the mutant Arabidopsis plant (tt7) did not contain quercetin, even under the enhanced UVB treatment. Under the low UVB treatment the total amount of flavonol was similar to the wild-type (Ler), but with increasing UVB, total flavonol (i.e. kaempferol) levels were significantly higher than in similarly treated wild type plants. In the Petunia F3'H mutant, low levels of quercetin were found even in the low UVB treatment, which indicates this variety may be producing some quercetin via an alternative pathway. Under UVB radiation, total flavonoids increased to levels significantly higher than in similarly treated wild type plants, and most of this material was kaempferol. These observations suggest that quercetin is the preferred protective flavonol in wild type plants, due perhaps to enhanced antioxidant or free radical scavenging activity. In mutant plants lacking the F3'H enzyme, the response is to produce a larger amount of a less effective photoprotectant

Uncompensated polyuria in a mouse model of Bartter's syndrome

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Takahashi, Nobuyuki; Chernavvsky, Daniel R.; Gomez, R. Ariel; Igarashi, Peter; Gitelman, Hillel J.; Smithies, Oliver

2000-01-01

We have used homologous recombination to disrupt the mouse gene coding for the NaK2Cl cotransporter (NKCC2) expressed in kidney epithelial cells of the thick ascending limb and macula densa. This gene is one of several that when mutated causes Bartter's syndrome in humans, a syndrome characterized by severe polyuria and electrolyte imbalance. Homozygous NKCC2−/− pups were born in expected numbers and appeared normal. However, by day 1 they showed signs of extracellular volume depletion (hematocrit 51%; wild type 37%). They subsequently failed to thrive. By day 7, they were small and markedly dehydrated and exhibited renal insufficiency, high plasma potassium, metabolic acidosis, hydronephrosis of varying severity, and high plasma renin concentrations. None survived to weaning. Treatment of −/− pups with indomethacin from day 1 prevented growth retardation and 10% treated for 3 weeks survived, although as adults they exhibited severe polyuria (10 ml/day), extreme hydronephrosis, low plasma potassium, high blood pH, hypercalciuria, and proteinuria. Wild-type mice treated with furosemide, an inhibitor of NaK2Cl cotransporters, have a phenotype similar to the indomethacin-rescued −/− adults except that hydronephrosis was mild. The polyuria, hypercalciuria, and proteinuria of the −/− adults and furosemide-treated wild-type mice were unresponsive to inhibitors of the renin angiotensin system, vasopressin, and further indomethacin. Thus absence of NKCC2 in the mouse causes polyuria that is not compensated elsewhere in the nephron. The NKCC2 mutant animals should be valuable for uncovering new pathophysiologic and therapeutic aspects of genetic disturbances in water and electrolyte recovery by the kidney. PMID:10779555

Effects of regionally applied heating on the respiration of wild type ...

African Journals Online (AJOL)

Nocturnal dark respiration (Rn) in wild type and transgenic soybean plants ... Illinois, USA under ambient and elevated CO2 conditions was examined in this study. ... Experimental plants were transferred to a controlled growth chamber at V4 ...

Comparative analysis of the protein compositions between wild type and body color mutant of helicoverpa armigera adult

International Nuclear Information System (INIS)

He Lihua; Chen Jin'e; Liu Yan; Wang Yongqiang; Liu Peigang; Meng Zhiqi

2012-01-01

To gain an in-depth understanding of the fineness and regulation mechanism of body color mutant of Helicoverpa armigera Hbner, the protein composition differences between adult of dominant mutant, recessive mutant and wild type were studied using the SDS-PAGE combined with MALDI-TOF-TOF/MS and bioinformatics analysis. The results indicated that the protein composition of the dominant mutant and wild type had little difference. However, there were obvious differences between the recessive mutant and wild-type. Three specific stripe were chosen for mass spectrometry and bioinformatics analysis, and two types of proteins related to energy metabolism and cytoskeleton were identified. These findings suggested that the two types of proteins may be associated with occurrence and regulation of body color mutant traits of H. armigera. (authors)

Wild-type MIC distributions for aminoglycoside and cyclic polypeptide antibiotics used for treatment of Mycobacterium tuberculosis infections.

Science.gov (United States)

Juréen, P; Angeby, K; Sturegård, E; Chryssanthou, E; Giske, C G; Werngren, J; Nordvall, M; Johansson, A; Kahlmeter, G; Hoffner, S; Schön, T

2010-05-01

The aminoglycosides and cyclic polypeptides are essential drugs in the treatment of multidrug-resistant tuberculosis, underscoring the need for accurate and reproducible drug susceptibility testing (DST). The epidemiological cutoff value (ECOFF) separating wild-type susceptible strains from non-wild-type strains is an important but rarely used tool for indicating susceptibility breakpoints against Mycobacterium tuberculosis. In this study, we established wild-type MIC distributions on Middlebrook 7H10 medium for amikacin, kanamycin, streptomycin, capreomycin, and viomycin using 90 consecutive clinical isolates and 21 resistant strains. Overall, the MIC variation between and within runs did not exceed +/-1 MIC dilution step, and validation of MIC values in Bactec 960 MGIT demonstrated good agreement. Tentative ECOFFs defining the wild type were established for all investigated drugs, including amikacin and viomycin, which currently lack susceptibility breakpoints for 7H10. Five out of seven amikacin- and kanamycin-resistant isolates were classified as susceptible to capreomycin according to the current critical concentration (10 mg/liter) but were non-wild type according to the ECOFF (4 mg/liter), suggesting that the critical concentration may be too high. All amikacin- and kanamycin-resistant isolates were clearly below the ECOFF for viomycin, and two of them were below the ECOFF for streptomycin, indicating that these two drugs may be considered for treatment of amikacin-resistant strains. Pharmacodynamic indices (peak serum concentration [Cmax]/MIC) were more favorable for amikacin and viomycin compared to kanamycin and capreomycin. In conclusion, our data emphasize the importance of establishing wild-type MIC distributions for improving the quality of drug susceptibility testing against Mycobacterium tuberculosis.

Comprehensive analysis of ultrasonic vocalizations in a mouse model of fragile X syndrome reveals limited, call type specific deficits.

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Snigdha Roy

Full Text Available Fragile X syndrome (FXS is a well-recognized form of inherited mental retardation, caused by a mutation in the fragile X mental retardation 1 (Fmr1 gene. The gene is located on the long arm of the X chromosome and encodes fragile X mental retardation protein (FMRP. Absence of FMRP in fragile X patients as well as in Fmr1 knockout (KO mice results, among other changes, in abnormal dendritic spine formation and altered synaptic plasticity in the neocortex and hippocampus. Clinical features of FXS include cognitive impairment, anxiety, abnormal social interaction, mental retardation, motor coordination and speech articulation deficits. Mouse pups generate ultrasonic vocalizations (USVs when isolated from their mothers. Whether those social ultrasonic vocalizations are deficient in mouse models of FXS is unknown. Here we compared isolation-induced USVs generated by pups of Fmr1-KO mice with those of their wild type (WT littermates. Though the total number of calls was not significantly different between genotypes, a detailed analysis of 10 different categories of calls revealed that loss of Fmr1 expression in mice causes limited and call-type specific deficits in ultrasonic vocalization: the carrier frequency of flat calls was higher, the percentage of downward calls was lower and that the frequency range of complex calls was wider in Fmr1-KO mice compared to their WT littermates.

Connective Tissue Growth Factor Transgenic Mouse Develops Cardiac Hypertrophy, Lean Body Mass and Alopecia.

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Nuglozeh, Edem

2017-07-01

Connective Tissue Growth Factor (CTGF/CCN2) is one of the six members of cysteine-rich, heparin-binding proteins, secreted as modular protein and recognised to play a major function in cell processes such as adhesion, migration, proliferation and differentiation as well as chondrogenesis, skeletogenesis, angiogenesis and wound healing. The capacity of CTGF to interact with different growth factors lends an important role during early and late development, especially in the anterior region of the embryo. CTGF Knockout (KO) mice have several craniofacial defects and bone miss shaped due to an impairment of the vascular system development during chondrogenesis. The aim of the study was to establish an association between multiple modular functions of CTGF and the phenotype and cardiovascular functions in transgenic mouse. Bicistronic cassette was constructed using pIRES expressing vector (Clontech, Palo Alto, CA). The construct harbours mouse cDNA in tandem with LacZ cDNA as a reporter gene under the control of Cytomegalovirus (CMV) promoter. The plasmid was linearised with NotI restriction enzyme, and 50 ng of linearised plasmid was injected into mouse pronucleus for the chimaera production. Immunohistochemical methods were used to assess the colocalisation renin and CTGF as well as morphology and rheology of the cardiovascular system. The chimeric mice were backcrossed against the wild-type C57BL/6 to generate hemizygous (F1) mouse. Most of the offsprings died as a result of respiratory distress and those that survived have low CTGF gene copy number, approximately 40 molecules per mouse genome. The copy number assessment on the dead pups showed 5×10 3 molecules per mouse genome explaining the threshold of the gene in terms of toxicity. Interestingly, the result of this cross showed 85% of the progenies to be positive deviating from Mendelian first law. All F2 progenies died excluding the possibility of establishing the CTGF transgenic mouse line, situation that

[Imaging anatomy of cranial nerves].

Science.gov (United States)

Hermier, M; Leal, P R L; Salaris, S F; Froment, J-C; Sindou, M

2009-04-01

Knowledge of the anatomy of the cranial nerves is mandatory for optimal radiological exploration and interpretation of the images in normal and pathological conditions. CT is the method of choice for the study of the skull base and its foramina. MRI explores the cranial nerves and their vascular relationships precisely. Because of their small size, it is essential to obtain images with high spatial resolution. The MRI sequences optimize contrast between nerves and surrounding structures (cerebrospinal fluid, fat, bone structures and vessels). This chapter discusses the radiological anatomy of the cranial nerves.

Sabin and wild type polioviruses from children who presented with acute flaccid paralysis in Nigeria.

Science.gov (United States)

Adedeji, A O; Okonko, I O; Adu, F D

2012-09-01

Sensitive poliovirus surveillance to detect vaccine-derived-polioviruses will continue to increase in importance. Isolating and identifying poliovirus strains from children of pediatrics age in Nigeria. A total of 120 fecal samples were randomly collected from children under the age of five who presented with acute flaccid paralysis. Samples were tested by tissue culture technique and further characterized by intratypic differentiation testing using ELISA and PCR methods. The study confirmed the presence of 22(18.3%) enteroviral isolates comprising 19(86.4%) polioviruses and 3(13.6%) non-polio enteroviruses. These 19 polioviruses include: Sabin-type poliovirus-1 (15.8%), poliovirus-2 (10.5%), poliovirus-3 (10.5%) and wild-type poliovirus-1 (63.2%) isolates. It showed that poliovirus infection was higher in children ages 6-11 months (18.9%), females (18.4%), northern states (91.0%) with no vaccination record (75.0%). Wild-type poliovirus-1 was isolated from the stool samples of 12(54.6%) children from northern states and in all age groups except 18-23 months. No significant differences (P >0.05) between poliovirus infection and age (18.9% vs. 17.7%; 81.9% vs. 18.2%) and sex (18.3% vs. 18.4%). There was significant differences (Pvaccination (75.0% vs. 0.0%). No wild-type poliovirus was found in those with complete vaccination. This study further confirms the presence of Sabin and wild-type poliovirus among children in Nigeria. The isolation of Sabin strain of poliovirus is advantageous to the polio eradication program as it is capable of inducing natural immunity in susceptible hosts. Transmission of wild-type poliovirus among children with incomplete vaccination poses a serious threat to polio eradication program in Nigeria. Environmental and serological surveillance with larger sample size are important for monitoring poliovirus circulation in Nigeria.

Repair of gamma radiation damage in wild type and a radiation sensitive mutant of Deinococcus radiodurans

International Nuclear Information System (INIS)

Mizuma, Nagayo

1989-01-01

In an effort to examine production and repair of radiation-induced single and double strand breaks in the DNA, a repair-deficient wild type and a repair-deficient mutant, UV17, of Deinococcus radiodurans were subjected to Co-60 gamma irradiation at a dose rate of 6.3 kGy/hr for wild type and 3.9 kGy/hr for UV17 mutant. The shoulder of the curve of UV17 mutant was narrow but existed with the intercept of 0.7 kGy and the corresponding value of the wild type was 4.2 kGy. Mutant cells exhibited about 6 fold increases in sensitivity for the shoulder relative to the wild type. The D 37 doses in the wild type and the mutant were 0.57 kGy and 0.25 kGy, respectively. From the survival curves, difference in the sensitivity between two strains was mainly due to difference of repair capacity than the number of radiation sensitive target. Sedimentation rate of the main component in the irradiated cells of UV17 mutant increased almost to the level of unirradiated control by the postincubation at 30deg C for 3 hrs. The results indicated that this sensitive mutant also exhibited an ability to restore single strand breaks after exposure to a sublethal dose of 0.6 kGy. When restitution of double strand breaks was analyzed by sedimentation in a neutral sucrose gradient, the wild type showed restitution to DNA-membrane complex from large part of the breaks. For UV17 mutant, the apparent increase in DNA-membrane complex formation was seen after 3 hours incubation. Large part of the decrease in the activities of peak 2 was recovered in the peak 1 for the wild type. For the mutant, there was little restitution to peak 1. Almost free DNA component in UV17 mutant, therefore, was merely degraded into shorter pieces. Restoration of DNA-membrane complex from free DNA derived from gamma-ray induced double strand scission involved closely in the repair of gamma-induced damage and survival. (N.K.)

Multiple Cranial Nerve Involvement In Cryptococcal Meningitis

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Mahadevan A

2000-01-01

Full Text Available Cryptococcal meningitis is an uncommon cause of multiple cranial nerve palsies. This case report illustrates one such case of cryptococcal meningitis clinically manifesting with extensive cranial nerve involvement in an HIV seronegative individual. Histology revealed infiltration of the cranial nerves by cryptococci causing axonal disruption with secondary demyelination in the absence of any evidence of inflammation or vasculitis. We believe that axonal damage underlies the pathogenesis of cranial nerve involvement in cryptococcal meningitis.

Cranial Bosses of Choerosaurus dejageri (Therapsida, Therocephalia): Earliest Evidence of Cranial Display Structures in Eutheriodonts.

Science.gov (United States)

Benoit, Julien; Manger, Paul R; Fernandez, Vincent; Rubidge, Bruce S

2016-01-01

Choerosaurus dejageri, a non-mammalian eutheriodont therapsid from the South African late Permian (~259 Ma), has conspicuous hemispheric cranial bosses on the maxilla and the mandible. These bosses, the earliest of this nature in a eutheriodont, potentially make C. dejageri a key species for understanding the evolutionary origins of sexually selective behaviours (intraspecific competition, ritualized sexual and intimidation displays) associated with cranial outgrowths at the root of the clade that eventually led to extant mammals. Comparison with the tapinocephalid dinocephalian Moschops capensis, a therapsid in which head butting is strongly supported, shows that the delicate structure of the cranial bosses and the gracile structure of the skull of Choerosaurus would be more suitable for display and low energy combat than vigorous head butting. Thus, despite the fact that Choerosaurus is represented by only one skull (which makes it impossible to address the question of sexual dimorphism), its cranial bosses are better interpreted as structures involved in intraspecific selection, i.e. low-energy fighting or display. Display structures, such as enlarged canines and cranial bosses, are widespread among basal therapsid clades and are also present in the putative basal therapsid Tetraceratops insignis. This suggests that sexual selection may have played a more important role in the distant origin and evolution of mammals earlier than previously thought. Sexual selection may explain the subsequent independent evolution of cranial outgrowths and pachyostosis in different therapsid lineages (Biarmosuchia, Dinocephalia, Gorgonopsia and Dicynodontia).

Cranial Bosses of Choerosaurus dejageri (Therapsida, Therocephalia: Earliest Evidence of Cranial Display Structures in Eutheriodonts.

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Julien Benoit

Full Text Available Choerosaurus dejageri, a non-mammalian eutheriodont therapsid from the South African late Permian (~259 Ma, has conspicuous hemispheric cranial bosses on the maxilla and the mandible. These bosses, the earliest of this nature in a eutheriodont, potentially make C. dejageri a key species for understanding the evolutionary origins of sexually selective behaviours (intraspecific competition, ritualized sexual and intimidation displays associated with cranial outgrowths at the root of the clade that eventually led to extant mammals. Comparison with the tapinocephalid dinocephalian Moschops capensis, a therapsid in which head butting is strongly supported, shows that the delicate structure of the cranial bosses and the gracile structure of the skull of Choerosaurus would be more suitable for display and low energy combat than vigorous head butting. Thus, despite the fact that Choerosaurus is represented by only one skull (which makes it impossible to address the question of sexual dimorphism, its cranial bosses are better interpreted as structures involved in intraspecific selection, i.e. low-energy fighting or display. Display structures, such as enlarged canines and cranial bosses, are widespread among basal therapsid clades and are also present in the putative basal therapsid Tetraceratops insignis. This suggests that sexual selection may have played a more important role in the distant origin and evolution of mammals earlier than previously thought. Sexual selection may explain the subsequent independent evolution of cranial outgrowths and pachyostosis in different therapsid lineages (Biarmosuchia, Dinocephalia, Gorgonopsia and Dicynodontia.

Genetic recombination of tick-borne flaviviruses among wild-type strains.

Science.gov (United States)

Norberg, Peter; Roth, Anette; Bergström, Tomas

2013-06-05

Genetic recombination has been suggested to occur in mosquito-borne flaviviruses. In contrast, tick-borne flaviviruses have been thought to evolve in a clonal manner, although recent studies suggest that recombination occurs also for these viruses. We re-analyzed the data and found that previous conclusions on wild type recombination were probably falsely drawn due to misalignments of nucleotide sequences, ambiguities in GenBank sequences, or different laboratory culture histories suggestive of recombination events in laboratory. To evaluate if reliable predictions of wild type recombination of tick-borne flaviviruses can be made, we analyzed viral strains sequenced exclusively for this study, and other flavivirus sequences retrieved from GenBank. We detected genetic signals supporting recombination between viruses within the three clades of TBEV-Eu, TBEV-Sib and TBEV-Fe, respectively. Our results suggest that the tick-borne encephalitis viruses may undergo recombination under natural conditions, but that geographic barriers restrict most recombination events to involve only closely genetically related viruses. Copyright © 2013 Elsevier Inc. All rights reserved.

Prednisolone-induced differential gene expression in mouse liver carrying wild type or a dimerization-defective glucocorticoid receptor

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Dokter Wim

2010-06-01

Full Text Available Abstract Background Glucocorticoids (GCs control expression of a large number of genes via binding to the GC receptor (GR. Transcription may be regulated either by binding of the GR dimer to DNA regulatory elements or by protein-protein interactions of GR monomers with other transcription factors. Although the type of regulation for a number of individual target genes is known, the relative contribution of both mechanisms to the regulation of the entire transcriptional program remains elusive. To study the importance of GR dimerization in the regulation of gene expression, we performed gene expression profiling of livers of prednisolone-treated wild type (WT and mice that have lost the ability to form GR dimers (GRdim. Results The GR target genes identified in WT mice were predominantly related to glucose metabolism, the cell cycle, apoptosis and inflammation. In GRdim mice, the level of prednisolone-induced gene expression was significantly reduced compared to WT, but not completely absent. Interestingly, for a set of genes, involved in cell cycle and apoptosis processes and strongly related to Foxo3a and p53, induction by prednisolone was completely abolished in GRdim mice. In contrast, glucose metabolism-related genes were still modestly upregulated in GRdim mice upon prednisolone treatment. Finally, we identified several novel GC-inducible genes from which Fam107a, a putative histone acetyltransferase complex interacting protein, was most strongly dependent on GR dimerization. Conclusions This study on prednisolone-induced effects in livers of WT and GRdim mice identified a number of interesting candidate genes and pathways regulated by GR dimers and sheds new light onto the complex transcriptional regulation of liver function by GCs.

Wild-Type MIC Distributions for Aminoglycoside and Cyclic Polypeptide Antibiotics Used for Treatment of Mycobacterium tuberculosis Infections▿

Science.gov (United States)

Juréen, P.; Ängeby, K.; Sturegård, E.; Chryssanthou, E.; Giske, C. G.; Werngren, J.; Nordvall, M.; Johansson, A.; Kahlmeter, G.; Hoffner, S.; Schön, T.

2010-01-01

The aminoglycosides and cyclic polypeptides are essential drugs in the treatment of multidrug-resistant tuberculosis, underscoring the need for accurate and reproducible drug susceptibility testing (DST). The epidemiological cutoff value (ECOFF) separating wild-type susceptible strains from non-wild-type strains is an important but rarely used tool for indicating susceptibility breakpoints against Mycobacterium tuberculosis. In this study, we established wild-type MIC distributions on Middlebrook 7H10 medium for amikacin, kanamycin, streptomycin, capreomycin, and viomycin using 90 consecutive clinical isolates and 21 resistant strains. Overall, the MIC variation between and within runs did not exceed ±1 MIC dilution step, and validation of MIC values in Bactec 960 MGIT demonstrated good agreement. Tentative ECOFFs defining the wild type were established for all investigated drugs, including amikacin and viomycin, which currently lack susceptibility breakpoints for 7H10. Five out of seven amikacin- and kanamycin-resistant isolates were classified as susceptible to capreomycin according to the current critical concentration (10 mg/liter) but were non-wild type according to the ECOFF (4 mg/liter), suggesting that the critical concentration may be too high. All amikacin- and kanamycin-resistant isolates were clearly below the ECOFF for viomycin, and two of them were below the ECOFF for streptomycin, indicating that these two drugs may be considered for treatment of amikacin-resistant strains. Pharmacodynamic indices (peak serum concentration [Cmax]/MIC) were more favorable for amikacin and viomycin compared to kanamycin and capreomycin. In conclusion, our data emphasize the importance of establishing wild-type MIC distributions for improving the quality of drug susceptibility testing against Mycobacterium tuberculosis. PMID:20237102

Cranial nerve involvement in nasopharyngeal carcinoma

International Nuclear Information System (INIS)

Oezyar, E.; Atahan, I.L.; Akyol, F.H.; Guerkaynak, M.; Zorlu, A.F.

1994-01-01

Between 1975 and 1989, 23 nasopharyngeal carcinoma patients presenting with cranial nerve involvement (CNI) of one or more nerves at the time of diagnosis were treated and followed-up in our department. All patients were irradiated with curative intent, and total doses of 50 to 70 Gy (median 65 Gy) were delivered to the nasopharynx. Cranial nerves VI, III, V, IV, IX, and XII were the most commonly involved nerves. The total response rate of cranial nerves was 74% in a median follow-up time of 2 years, with the highest rate observed in the third and sixth cranial nerves. All complete responses except two were observed in the first month after radiotherapy. (author)

Comparative effects of chlorpyrifos in wild type and cannabinoid Cb1 receptor knockout mice

Energy Technology Data Exchange (ETDEWEB)

Baireddy, Praveena; Liu, Jing; Hinsdale, Myron; Pope, Carey, E-mail: carey.pope@okstate.edu

2011-11-15

Endocannabinoids (eCBs) modulate neurotransmission by inhibiting the release of a variety of neurotransmitters. The cannabinoid receptor agonist WIN 55.212-2 (WIN) can modulate organophosphorus (OP) anticholinesterase toxicity in rats, presumably by inhibiting acetylcholine (ACh) release. Some OP anticholinesterases also inhibit eCB-degrading enzymes. We studied the effects of the OP insecticide chlorpyrifos (CPF) on cholinergic signs of toxicity, cholinesterase activity and ACh release in tissues from wild type (+/+) and cannabinoid CB1 receptor knockout (-/-) mice. Mice of both genotypes (n = 5-6/treatment group) were challenged with CPF (300 mg/kg, 2 ml/kg in peanut oil, sc) and evaluated for functional and neurochemical changes. Both genotypes exhibited similar cholinergic signs and cholinesterase inhibition (82-95% at 48 h after dosing) in cortex, cerebellum and heart. WIN reduced depolarization-induced ACh release in vitro in hippocampal slices from wild type mice, but had no effect in hippocampal slices from knockouts or in striatal slices from either genotype. Chlorpyrifos oxon (CPO, 100 {mu}M) reduced release in hippocampal slices from both genotypes in vitro, but with a greater reduction in tissues from wild types (21% vs 12%). CPO had no significant in vitro effect on ACh release in striatum. CPF reduced ACh release in hippocampus from both genotypes ex vivo, but reduction was again significantly greater in tissues from wild types (52% vs 36%). In striatum, CPF led to a similar reduction (20-23%) in tissues from both genotypes. Thus, while CB1 deletion in mice had little influence on the expression of acute toxicity following CPF, CPF- or CPO-induced changes in ACh release appeared sensitive to modulation by CB1-mediated eCB signaling in a brain-regional manner. -- Highlights: Black-Right-Pointing-Pointer C57Bl/6 mice showed dose-related cholinergic toxicity following subcutaneous chlorpyrifos exposure. Black-Right-Pointing-Pointer Wild type and

Comparative effects of chlorpyrifos in wild type and cannabinoid Cb1 receptor knockout mice

International Nuclear Information System (INIS)

Baireddy, Praveena; Liu, Jing; Hinsdale, Myron; Pope, Carey

2011-01-01

Endocannabinoids (eCBs) modulate neurotransmission by inhibiting the release of a variety of neurotransmitters. The cannabinoid receptor agonist WIN 55.212-2 (WIN) can modulate organophosphorus (OP) anticholinesterase toxicity in rats, presumably by inhibiting acetylcholine (ACh) release. Some OP anticholinesterases also inhibit eCB-degrading enzymes. We studied the effects of the OP insecticide chlorpyrifos (CPF) on cholinergic signs of toxicity, cholinesterase activity and ACh release in tissues from wild type (+/+) and cannabinoid CB1 receptor knockout (−/−) mice. Mice of both genotypes (n = 5–6/treatment group) were challenged with CPF (300 mg/kg, 2 ml/kg in peanut oil, sc) and evaluated for functional and neurochemical changes. Both genotypes exhibited similar cholinergic signs and cholinesterase inhibition (82–95% at 48 h after dosing) in cortex, cerebellum and heart. WIN reduced depolarization-induced ACh release in vitro in hippocampal slices from wild type mice, but had no effect in hippocampal slices from knockouts or in striatal slices from either genotype. Chlorpyrifos oxon (CPO, 100 μM) reduced release in hippocampal slices from both genotypes in vitro, but with a greater reduction in tissues from wild types (21% vs 12%). CPO had no significant in vitro effect on ACh release in striatum. CPF reduced ACh release in hippocampus from both genotypes ex vivo, but reduction was again significantly greater in tissues from wild types (52% vs 36%). In striatum, CPF led to a similar reduction (20–23%) in tissues from both genotypes. Thus, while CB1 deletion in mice had little influence on the expression of acute toxicity following CPF, CPF- or CPO-induced changes in ACh release appeared sensitive to modulation by CB1-mediated eCB signaling in a brain-regional manner. -- Highlights: ► C57Bl/6 mice showed dose-related cholinergic toxicity following subcutaneous chlorpyrifos exposure. ► Wild type and cannabinoid CB1 receptor knockout littermates

Epidemiological approach to emergent cranial surgery of cranial traumas

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Hülagü Kaptan

2008-03-01

Full Text Available

Objective: In this study, we aim to define the emergent cranial surgery of cranial trauma cases in terms of the reason of occurance, diagnosis, prognostic factors and results. Methods: 153 cases hospitalized in our clinic during a four year period were statistically analysed in accordance with trauma etiology, age, gender, application GCS (Glascow Coma Score mortality rate, location and established patology.

Results: 76% (116 of the 153 cases were male. The most frequent etiological reasons were, in descending order, traffic accident 52% (n = 80, fall 34% (n = 53, direct trauma to the head 14(n =20. 45% (n = 69 were diagnosed epidural haematomas, 26% (n = 40 were diagnosed depression fractures and 3% (n = 5 were diagnosed intracerebral haematomas. A meaningful statistical difference was found in the comparison of the diagnosis regarding gender (p=0,012 age group (p=0,0282 and GCS (p=0,0001.

Conclusions: In order to prevent cranial traumas, studies aimed at minimizing traffic accidents should be undertaken. The most essential action after the accident has occured is triage, and this is of great importance in order to establish communication among the health institutions.

Spaceflight influences both mucosal and peripheral cytokine production in PTN-Tg and wild type mice.

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Justin L McCarville

Full Text Available Spaceflight is associated with several health issues including diminished immune efficiency. Effects of long-term spaceflight on selected immune parameters of wild type (Wt and transgenic mice over-expressing pleiotrophin under the human bone-specific osteocalcin promoter (PTN-Tg were examined using the novel Mouse Drawer System (MDS aboard the International Space Station (ISS over a 91 day period. Effects of this long duration flight on PTN-Tg and Wt mice were determined in comparison to ground controls and vivarium-housed PTN-Tg and Wt mice. Levels of interleukin-2 (IL-2 and transforming growth factor-beta1 (TGF-β1 were measured in mucosal and systemic tissues of Wt and PTN-Tg mice. Colonic contents were also analyzed to assess potential effects on the gut microbiota, although no firm conclusions could be made due to constraints imposed by the MDS payload and the time of sampling. Spaceflight-associated differences were observed in colonic tissue and systemic lymph node levels of IL-2 and TGF-β1 relative to ground controls. Total colonic TGF-β1 levels were lower in Wt and PTN-Tg flight mice in comparison to ground controls. The Wt flight mouse had lower levels of IL-2 and TGF-β1 compared to the Wt ground control in both the inguinal and brachial lymph nodes, however this pattern was not consistently observed in PTN-Tg mice. Vivarium-housed Wt controls had higher levels of active TGF-β1 and IL-2 in inguinal lymph nodes relative to PTN-Tg mice. The results of this study suggest compartmentalized effects of spaceflight and on immune parameters in mice.

PET imaging of brain with the {beta}-amyloid probe, [{sup 11}C]6-OH-BTA-1, in a transgenic mouse model of Alzheimer's disease

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Toyama, Hiroshi [Fujita Health University, Department of Radiology, Aichi (Japan); National Institutes of Health, Molecular Imaging Branch, National Institute of Mental Health, Bethesda, Maryland (United States); Ye, Daniel; Cohen, Robert M. [National Institutes of Health, Geriatric Psychiatry Branch, National Institute of Mental Health, Bethesda, Maryland (United States); Ichise, Masanori; Liow, Jeih-San; Cai, Lisheng; Musachio, John L.; Hong, Jinsoo; Crescenzo, Mathew; Tipre, Dnyanesh; Lu, Jian-Qiang; Zoghbi, Sami; Vines, Douglass C.; Pike, Victor W.; Innis, Robert B. [National Institutes of Health, Molecular Imaging Branch, National Institute of Mental Health, Bethesda, Maryland (United States); Jacobowitz, David [USUHS, Department of Anatomy, Physiology, and Genetics, Bethesda, Maryland (United States); Seidel, Jurgen; Green, Michael V. [National Institutes of Health, Department of Nuclear Medicine, Warren Grant Magnuson Clinical Center, Bethesda, Maryland (United States); Katada, Kazuhiro [Fujita Health University, Department of Radiology, Aichi (Japan)

2005-04-01

The purpose of this study was to evaluate the capacity of [{sup 11}C]6-OH-BTA-1 and positron emission tomography (PET) to quantify {beta}-amyloid (A{beta}) plaques in the Tg2576 mouse model of Alzheimer's disease (AD). PET imaging was performed with the NIH ATLAS small animal scanner in six elderly transgenic mice (Tg2576; age 22.0{+-}1.8 months; 23.6{+-}2.6 g) overexpressing a mutated form of human {beta}-amyloid precursor protein (APP) known to result in the production of A{beta} plaques, and in six elderly wild-type litter mates (age 21.8{+-}1.6 months; 29.5{+-}4.7 g). Dynamic PET scans were performed for 30 min in each mouse under 1% isoflurane inhalation anesthesia after a bolus injection of 13-46 MBq of [{sup 11}C]6-OH-BTA-1. PET data were reconstructed with 3D OSEM. On the coronal PET image, irregular regions of interest (ROIs) were placed on frontal cortex (FR), parietal cortex (PA), striatum (ST), thalamus (TH), pons (PO), and cerebellum (CE), guided by a mouse stereotaxic atlas. Time-activity curves (TACs) (expressed as percent injected dose per gram normalized to body weight: % ID-kg/g) were obtained for FR, PA, ST, TH, PO, and CE. ROI-to-CE radioactivity ratios were also calculated. Following PET scans, sections of mouse brain prepared from anesthetized and fixative-perfused mice were stained with thioflavin-S. TACs for [{sup 11}C]6-OH-BTA-1 in all ROIs peaked early (at 30-55 s), with radioactivity washing out quickly thereafter in both transgenic and wild-type mice. Peak uptake in all regions was significantly lower in transgenic mice than in wild-type mice. During the later part of the washout phase (12-30 min), the mean FR/CE and PA/CE ratios were higher in transgenic than in wild-type mice (1.06{+-}0.04 vs 0.98{+-}0.07, p=0.04; 1.06{+-}0.09 vs 0.93{+-}0.08 p=0.02) while ST/CE, TH/CE, and PO/CE ratios were not. Ex vivo staining revealed widespread A{beta} plaques in cortex, but not in cerebellum of transgenic mice or in any brain regions of wild-type

Familial Idiopathic Cranial Neuropathy in a Chinese Family.

Science.gov (United States)

Zhang, Li; Liang, Jianfeng; Yu, Yanbing

Cranial neuropathy is usually idiopathic and familial cases are uncommon. We describe a family with 5 members with cranial neuropathy over 3 generations. All affected patients were women, indicating an X-linked dominant or an autosomal dominant mode of inheritance. Our cases and a review of the literature suggest that familial idiopathic cranial neuropathy is a rare condition which may be related to autosomal dominant vascular disorders (e.g. vascular tortuosity, sclerosis, elongation or extension), small posterior cranial fossas, anatomical variations of the posterior circulation, hypersensitivity of cranial nerves and other abnormalities. Moreover, microvascular decompression is the treatment of choice because vascular compression is the main factor in the pathogenesis. To the best of our knowledge, this is the first report of familial cranial neuropathy in China.

Research on the ultrafast fluorescence property of thylakoid membranes of the wild-type and mutant rice

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Ren, Zhao-Yu; Xu, Xiao-Ming; Wang, Shui-Cai; Xin, Yue-Yong; He, Jun-Fang; Hou, Xun

2003-10-01

A high yielding rice variety mutant (Oryza sativa L., Zhenhui 249) with low chlorophyll b (Chl b) has been discovered in natural fields. It has a quality character controlled by a pair of recessive genes (nuclear gene). The partial loss of Chl b in content affects the efficiency of light harvest in a light harvest complex (LHC), thus producing the difference of the exciting energy transfer and the efficiency of photochemistry conversion between the mutant and wild-type rice in photosynthetic unit. The efficiency of utilizing light energy is higher in the mutant than that in the wild-type rice relatively. For further discussion of the above-mentioned difference and learning about the mechanism of the increase in the photochemical efficiency of the mutant, the pico-second resolution fluorescence spectrum measurement with delay-frame-scanning single photon counting technique is adopted. Thylakoid membranes of the mutant and the wild-type rice are excited by an Ar+ laser with a pulse width of 120 ps, repetition rate of 4 MHz and wavelength of 514 nm. Compared with the time and spectrum property of exciting fluorescence, conclusions of those ultrafast dynamic experiments are: 1) The speeds of the exciting energy transferred in photo-system I are faster than that in photo-system II in both samples. 2) The speeds of the exciting energy transfer of mutant sample are faster than those of the wild-type. This might be one of the major reasons why the efficiency of photosynthesis is higher in mutant than that in the wild-type rice.

The imaging manifestation of intracranial schwannomas not arising from cranial nerves

International Nuclear Information System (INIS)

Luo Boning; Sun Gengxi; Liang Kangfu

2003-01-01

Objective: To report 4 cases of operation-confirmed intracranial schwannomas not arising from cranial nerves, and to discuss the histogenesis and CT and MRI manifestation combining with the literature. Methods: CT and MRI findings of these 4 intracranial schwannomas were analyzed retrospectively and their pathologic characteristics were reviewed. Results: The tumors demonstrated low-iso mixed density with necrotic and cystic areas. Large degeneration even became the prominent characteristics on CT scan. Low-signal to iso-signal intensity on T 1 -weighted images and heterogeneous high-signal intensity on T 2 -weighted images were revealed. The solid portion and the wall of the tumors were moderately enhanced on enhanced CT and MRI scans. Hematoxylin and eosin-stained sections showed two corresponding histological patterns: Antoni Type A and Antoni Type B pattern. The tumor cells exhibited a strong positive staining pattern for s-100 protein. Conclusion: The imaging manifestations of these tumors were similar to that of cranial nerve schwannomas except that the former had higher cystic degeneration rate. We should take that diagnosis into consideration when the mass is not located on cranial nerve but its image feature resembles schwannomas

Use of Multidirectional Cranial Distraction Osteogenesis for Cranial Expansion in Syndromic Craniosynostosis

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Ataru Sunaga, MD

2017-12-01

Full Text Available Summary:. Patients with syndromic craniosynostosis often require a large amount of cranial expansion to avoid intracranial hypertension, but the surgical procedure remains controversial. A patient of severe syndromic craniosynostosis with multiple bony defects and anomalous venous drainage at the occipital region was treated by multidirectional cranial distraction osteogenesis (MCDO at the age of 8 months. Distraction started 5 days after surgery and ceased on postoperative day 16. The distraction devices were removed 27 days after completing distraction. After device removal, the increase of intracranial volume was 155 ml and the cephalic index was improved from 115.5 to 100.5. The resultant cranial shape was well maintained with minimal relapse at postoperative 9 months. In cases of syndromic craniosynostosis with multiple bony defects and/or anomalous venous drainage at the occipital region, expansion of the anterior cranium by MCDO is a viable alternative to conventional methods.

Structural Characterization of Lignin in Wild-Type versus COMT Down-Regulated Switchgrass

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Samuel, Reichel [School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, GA (United States); BioEnergy Science Center, Oak Ridge, TN (United States); Pu, Yunqiao, E-mail: yunqiao.pu@ipst.gatech.edu [BioEnergy Science Center, Oak Ridge, TN (United States); Institute of Paper Science and Technology, Georgia Institute of Technology, Atlanta, GA (United States); Jiang, Nan [School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, GA (United States); BioEnergy Science Center, Oak Ridge, TN (United States); Fu, Chunxiang [Forage Improvement Division, The Samuel Roberts Noble Foundation, Ardmore, OK (United States); Wang, Zeng-Yu [BioEnergy Science Center, Oak Ridge, TN (United States); Forage Improvement Division, The Samuel Roberts Noble Foundation, Ardmore, OK (United States); Ragauskas, Arthur, E-mail: yunqiao.pu@ipst.gatech.edu [School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, GA (United States); BioEnergy Science Center, Oak Ridge, TN (United States)

2014-01-20

This study examined the chemical structural characteristics of cellulolytic enzyme lignin isolated from switchgrass focusing on comparisons between wild-type control and caffeic acid 3-O-methyltransferase (COMT) down-regulated transgenic line. Nuclear magnetic resonance techniques including {sup 13}C, {sup 31}P, and two-dimensional {sup 13}C-{sup 1}H heteronuclear single quantum coherence as well as gel permeation chromatography were employed. Compared to the wild-type, the COMT down-regulated transgenic switchgrass lignin demonstrated a decrease in syringyl (S):guaiacyl (G) ratio and p-coumarate:ferulate ratio, an increase in relative abundance of phenylcoumaran unit, and a comparable content of total free phenolic OH groups along with formation of benzodioxane unit. In addition, COMT down-regulation had no significant effects on the lignin molecular weights during its biosynthesis process.

Restricted replication of coronavirus MHV-A59 in primary mouse brain astrocytes correlates with reduced pathogenicity

NARCIS (Netherlands)

Horzinek, M.C.; Berlo, M.F. van; Wolswijk, G.; Calafat, G.; Zeijst, B.A.M. van der

1986-01-01

Temperature-sensitive (ts) mutants of mouse hepatitis virus A59 (MHV-A59) are drastically attenuated in their pathogenic properties. Intracerebral inoculation of mice with 10(5) PFU of mutant ts342 results in prolonged infection of the central nervous system, whereas 100 PFU of wild-type virus are

An emerging role for misfolded wild-type SOD1 in sporadic ALS pathogenesis

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Melissa S Rotunno

2013-12-01

Full Text Available Amyotrophic lateral sclerosis (ALS is a fatal neurodegenerative disorder that targets motor neurons, leading to paralysis and death within a few years of disease onset. While several genes have been linked to the inheritable, or familial, form of ALS, much less is known about the cause(s of sporadic ALS, which accounts for approximately 90% of ALS cases. Due to the clinical similarities between familial and sporadic ALS, it is plausible that both forms of the disease converge on a common pathway and, therefore, involve common factors. Recent evidence suggests the Cu,Zn-superoxide dismutase (SOD1 protein to be one such factor that is common to both sporadic and familial ALS. In 1993, mutations were uncovered in SOD1 that represent the first known genetic cause of familial ALS. While the exact mechanism of mutant-SOD1 toxicity is still not known today, most evidence points to a gain of toxic function that stems, at least in part, from the propensity of this protein to misfold. In the wild-type SOD1 protein, non-genetic perturbations such as metal depletion, disruption of the quaternary structure, and oxidation, can also induce SOD1 to misfold. In fact, these aforementioned post-translational modifications cause wild-type SOD1 to adopt a toxic conformation that is similar to familial ALS-linked SOD1 variants. These observations, together with the detection of misfolded wild-type SOD1 within human post-mortem sporadic ALS samples, have been used to support the controversial hypothesis that misfolded forms of wild-type SOD1 contribute to sporadic ALS pathogenesis. In this review, we present data from the literature that both support and contradict this hypothesis. We also discuss SOD1 as a potential therapeutic target for both familial and sporadic ALS.

Electrophysiology of Cranial Nerve Testing: Cranial Nerves IX and X.

Science.gov (United States)

Martinez, Alberto R M; Martins, Melina P; Moreira, Ana Lucila; Martins, Carlos R; Kimaid, Paulo A T; França, Marcondes C

2018-01-01

The cranial nerves IX and X emerge from medulla oblongata and have motor, sensory, and parasympathetic functions. Some of these are amenable to neurophysiological assessment. It is often hard to separate the individual contribution of each nerve; in fact, some of the techniques are indeed a composite functional measure of both nerves. The main methods are the evaluation of the swallowing function (combined IX and X), laryngeal electromyogram (predominant motor vagal function), and heart rate variability (predominant parasympathetic vagal function). This review describes, therefore, the techniques that best evaluate the major symptoms presented in IX and X cranial nerve disturbance: dysphagia, dysphonia, and autonomic parasympathetic dysfunction.

Construction of a viral T2A-peptide based knock-in mouse model for enhanced Cre recombinase activity and fluorescent labeling of podocytes.

Science.gov (United States)

Koehler, Sybille; Brähler, Sebastian; Braun, Fabian; Hagmann, Henning; Rinschen, Markus M; Späth, Martin R; Höhne, Martin; Wunderlich, F Thomas; Schermer, Bernhard; Benzing, Thomas; Brinkkoetter, Paul T

2017-06-01

Podocyte injury is a key event in glomerular disease leading to proteinuria and opening the path toward glomerular scarring. As a consequence, glomerular research strives to discover molecular mechanisms and signaling pathways affecting podocyte health. The hNphs2.Cre mouse model has been a valuable tool to manipulate podocyte-specific genes and to label podocytes for lineage tracing and purification. Here we designed a novel podocyte-specific tricistronic Cre mouse model combining codon improved Cre expression and fluorescent cell labeling with mTomato under the control of the endogenous Nphs2 promoter using viral T2A-peptides. Independent expression of endogenous podocin, codon improved Cre, and mTomato was confirmed by immunofluorescence, fluorescent activated cell sorting and protein analyses. Nphs2 pod.T2A.ciCre.T2A.mTomato/wild-type mice developed normally and did not show any signs of glomerular disease or off-target effects under basal conditions and in states of disease. Nphs2 pod.T2A.ciCre.T2A.mTomato/wild-type -mediated gene recombination was superior to conventional hNphs2.Cre mice-mediated gene recombination. Last, we compared Cre efficiency in a disease model by mating Nphs2 pod.T2A.ciCre.T2A.mTomato/wild-type and hNphs2.Cre mice to Phb2 fl/fl mice. The podocyte-specific Phb2 knockout by Nphs2 pod.T2A.ciCre.T2A.mTomato/wild-type mice resulted in an aggravated glomerular injury as compared to a podocyte-specific Phb2 gene deletion triggered by hNphs2.Cre. Thus, we generated the first tricistronic podocyte mouse model combining enhanced Cre recombinase efficiency and fluorescent labeling in podocytes without the need for additional matings with conventional reporter mouse lines. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

In vivo synaptic transmission and morphology in mouse models of Tuberous sclerosis, Fragile X syndrome, Neurofibromatosis type 1 and Costello syndrome.

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Tiantian eWang

2015-07-01

Full Text Available Defects in the rat sarcoma viral oncogene homolog (Ras/extracellular-signal-regulated kinase (ERK and the phosphatidylinositol 3-kinase (PI3K-mammalian target of rapamycin (mTOR signaling pathways are responsible for several neurodevelopmental disorders. These disorders are an important cause for intellectual disability; additional manifestations include autism spectrum disorder, seizures and brain malformations. Changes in synaptic function are thought to underlie the neurological conditions associated with these syndromes. We therefore studied morphology and in vivo synaptic transmission of the calyx of Held synapse, a relay synapse in the medial nucleus of the trapezoid body (MNTB of the auditory brainstem, in mouse models of Tuberous sclerosis (TSC, Fragile X syndrome (FXS, Neurofibromatosis type 1 (NF1 and Costello syndrome (CS. Calyces from both Tsc1+/- and from Fmr1 knock-out (KO mice showed increased volume and surface area compared to wild-type (WT controls. In addition, in Fmr1 KO animals a larger fraction of calyces showed complex morphology. In MNTB principal neurons of Nf1+/- mice the average delay between EPSPs and APs was slightly smaller compared to wild-type controls, which could indicate an increased excitability. Otherwise, no obvious changes in synaptic transmission or short-term plasticity were observed during juxtacellular recordings in any of the four lines. Our results in these four mutants thus indicate that abnormalities of mTOR or Ras signaling do not necessarily result in changes in in vivo synaptic transmission.

Ameloblastin inhibits cranial suture closure by modulating MSX2 expression and proliferation.

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Phimon Atsawasuwan

Full Text Available Deformities of cranial sutures such as craniosynostosis and enlarged parietal foramina greatly impact human development and quality of life. Here we have examined the role of the extracellular matrix protein ameloblastin (Ambn, a recent addition to the family of non-collagenous extracellular bone matrix proteins, in craniofacial bone development and suture formation. Using RT-PCR, western blot and immunohistochemistry, Ambn was localized in mouse calvarial bone and adjacent condensed mesenchyme. Five-fold Ambn overexpression in a K14-driven transgenic mouse model resulted in delayed posterior frontal suture fusion and incomplete suture closure. Moreover, Ambn overexpressor skulls weighed 13.2% less, their interfrontal bones were 35.3% thinner, and the width between frontal bones plus interfrontal suture was 14.3% wider. Ambn overexpressing mice also featured reduced cell proliferation in suture blastemas and in mesenchymal cells from posterior frontal sutures. There was a more than 2-fold reduction of Msx2 in Ambn overexpressing calvariae and suture mesenchymal cells, and this effect was inversely proportionate to the level of Ambn overexpression in different cell lines. The reduction of Msx2 expression as a result of Ambn overexpression was further enhanced in the presence of the MEK/ERK pathway inhibitor O126. Finally, Ambn overexpression significantly reduced Msx2 down-stream target gene expression levels, including osteogenic transcription factors Runx2 and Osx, the bone matrix proteins Ibsp, ColI, Ocn and Opn, and the cell cycle-related gene CcnD1. Together, these data suggest that Ambn plays a crucial role in the regulation of cranial bone growth and suture closure via Msx 2 suppression and proliferation inhibition.

No evidence for functional inactivation of wild-type p53 protein by MDM2 overexpression in gastric carcinogenesis

NARCIS (Netherlands)

Blok, P.; Craanen, M. E.; Dekker, W.; Offerhaus, G. J.; Tytgat, G. N.

1998-01-01

Inactivation of wild-type p53 during gastric carcinogenesis is usually caused by mutations within exons 5-8 of the p53 gene leading to mutated, usually immunohistochemically detectable p53 proteins. However, functional inactivation of wild-type p53, mimicking mutational inactivation, may also result

Gene expression profiling in wild-type and metallothionein mutant fibroblast cell lines

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ÁNGELA D ARMENDÁRIZ

2006-01-01

Full Text Available The role of metallothioneins (MT in copper homeostasis is of great interest, as it appears to be partially responsible for the regulation of intracellular copper levels during adaptation to extracellular excess of the metal. To further investigate a possible role of MTs in copper metabolism, a genomics approach was utilized to evaluate the role of MT on gene expression. Microarray analysis was used to examine the effects of copper overload in fibroblast cells from normal and MT I and II double knock-out mice (MT-/-. As a first step, we compared genes that were significantly upregulated in wild-type and MT-/- cells exposed to copper. Even though wild-type and mutant cells are undistinguishable in terms of their morphological features and rates of growth, our results show that MT-/- cells do not respond with induction of typical markers of cellular stress under copper excess conditions, as observed in the wild-type cell line, suggesting that the transcription initiation rate or the mRNA stability of stress genes is affected when there is an alteration in the copper store capacity. The functional classification of other up-regulated genes in both cell lines indicates that a large proportion (>80% belong to two major categories: 1 metabolism; and 2 cellular physiological processes, suggesting that at the transcriptional level copper overload induces the expression of genes associated with diverse molecular functions. These results open the possibility to understand how copper homeostasis is being coordinated with other metabolic pathways.

Panitumumab and pegylated liposomal doxorubicin in platinum-resistant epithelial ovarian cancer with KRAS wild-type

DEFF Research Database (Denmark)

Steffensen, Karina Dahl; Waldstrøm, Marianne; Pallisgård, Niels

2013-01-01

OBJECTIVE: The increasing number of negative trials for ovarian cancer treatment has prompted an evaluation of new biologic agents, which in combination with chemotherapy may improve survival. The aim of this study was to investigate the response rate in platinum-resistant, KRAS wild-type ovarian...... cancer patients treated with pegylated liposomal doxorubicin (PLD) supplemented with panitumumab. PATIENTS AND METHODS: Major eligibility criteria were relapsed ovarian/fallopian/peritoneal cancer patients with platinum-resistant disease, measurable disease by GCIG CA125 criteria and KRAS wild-type...

Role of cranial imaging in epileptic status

International Nuclear Information System (INIS)

Nair, Pradeep P.; Kalita, Jayantee; Misra, Usha K.

2009-01-01

Introduction: There is paucity of studies evaluating the role of cranial imaging in the management of status epilepticus (SE); therefore this study evaluates the role of imaging in predicting the outcome of SE. Methods: Consecutive patients with SE were prospectively evaluated. Clinical evaluation, blood counts, serum chemistry and cerebrospinal fluid (CSF) were carried out. Cranial CT scan was performed on a spiral CT and MRI on a 1.5 T scanner. Patients were treated with IV sodium valproate, phenytoin and benzodiazepines as per fixed protocol. Outcome was defined as seizure control at 1 h and mortality. Various clinical and radiological parameters were correlated. Results: There were 99 patients with SE whose mean age was 35 (1-78) years, 40 females and 17 were below 12 years of age. Fifty six patients had central nervous system (CNS) infections, 15 strokes, 13 metabolic encephalopathy, 5 drug default and in the remaining 10 patients various acute symptomatic causes were present. Cranial imaging was abnormal in 59% patients. CT was abnormal in 21 (47.7%) out of 44 patients whereas MRI was abnormal in 26 (63.4%) out of 41 patients. Both MRI and CT were carried out in 14 patients and 12 revealed abnormalities; 2 had abnormality only on MRI. Imaging revealed cortical lesions in 10, subcortical in 19 and both cortical as well as subcortical in 30 patients. One hour seizure control was achieved in 60, seizures recurred within 24 h in 38 and 27 patients died during hospital stay. Seizure type, duration of SE, seizure control at 1 h and mortality did not correlate with radiological abnormalities. Conclusion: Cranial imaging reveals structural abnormality in 59% patients with SE and was not related to SE control and mortality.

Role of cranial imaging in epileptic status

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Nair, Pradeep P; Kalita, Jayantee [Department of Neurology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow 226014 (India); Misra, Usha K. [Department of Neurology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow 226014 (India)], E-mail: drukmisra@rediffmail.com

2009-06-15

Introduction: There is paucity of studies evaluating the role of cranial imaging in the management of status epilepticus (SE); therefore this study evaluates the role of imaging in predicting the outcome of SE. Methods: Consecutive patients with SE were prospectively evaluated. Clinical evaluation, blood counts, serum chemistry and cerebrospinal fluid (CSF) were carried out. Cranial CT scan was performed on a spiral CT and MRI on a 1.5 T scanner. Patients were treated with IV sodium valproate, phenytoin and benzodiazepines as per fixed protocol. Outcome was defined as seizure control at 1 h and mortality. Various clinical and radiological parameters were correlated. Results: There were 99 patients with SE whose mean age was 35 (1-78) years, 40 females and 17 were below 12 years of age. Fifty six patients had central nervous system (CNS) infections, 15 strokes, 13 metabolic encephalopathy, 5 drug default and in the remaining 10 patients various acute symptomatic causes were present. Cranial imaging was abnormal in 59% patients. CT was abnormal in 21 (47.7%) out of 44 patients whereas MRI was abnormal in 26 (63.4%) out of 41 patients. Both MRI and CT were carried out in 14 patients and 12 revealed abnormalities; 2 had abnormality only on MRI. Imaging revealed cortical lesions in 10, subcortical in 19 and both cortical as well as subcortical in 30 patients. One hour seizure control was achieved in 60, seizures recurred within 24 h in 38 and 27 patients died during hospital stay. Seizure type, duration of SE, seizure control at 1 h and mortality did not correlate with radiological abnormalities. Conclusion: Cranial imaging reveals structural abnormality in 59% patients with SE and was not related to SE control and mortality.

Bidirectional GPR119 agonism requires peptide YY and glucose for activity in mouse and human colon mucosa

DEFF Research Database (Denmark)

Tough, Iain R; Forbes, Sarah; Herzog, Herbert

2018-01-01

motility in wild-type (WT), GPR119-/- and PYY-/- mice.The water-soluble GPR119 agonist, AR440006 (that cannot traverse epithelial tight-junctions) elicited responses when added apically or basolaterally in mouse and human colonic mucosas. In both species, GPR119 responses were PYY, Y1 receptor...

Zebrafish Adar2 Edits the Q/R site of AMPA receptor Subunit gria2α transcript to ensure normal development of nervous system and cranial neural crest cells.

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I-Chen Li

Full Text Available BACKGROUND: Adar2 deaminates selective adenosines to inosines (A-to-I RNA editing in the double-stranded region of nuclear transcripts. Although the functions of mouse Adar2 and its biologically most important substrate gria2, encoding the GluA2 subunit of AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor, have been extensively studied, the substrates and functions of zebrafish Adar2 remain elusive. METHODS/PRINCIPAL FINDINGS: Expression of Adar2 was perturbed in the adar2 morphant (adar2MO, generated by antisense morpholio oligonucleotides. The Q/R editing of gria2α was reduced in the adar2MO and was enhanced by overexpression of Adar2, demonstrating an evolutionarily conserved activity between zebrafish and mammalian Adar2 in editing the Q/R site of gria2. To delineate the role of Q/R editing of gria2α in the developmental defects observed in the adar2MO, the Q/R editing of gria2α was specifically perturbed in the gria2αQRMO, generated by a morpholio oligonucleotide complementary to the exon complementary sequence (ECS required for the Q/R editing. Analogous to the adar2-deficient and Q/R-editing deficient mice displaying identical neurological defects, the gria2αQRMO and adar2MO displayed identical developmental defects in the nervous system and cranial cartilages. Knockdown p53 abolished apoptosis and partially suppressed the loss of spinal cord motor neurons in these morphants. However, reducing p53 activity neither replenished the brain neuronal populations nor rescued the developmental defects. The expressions of crestin and sox9b in the neural crest cells were reduced in the adar2MO and gria2αQRMO. Overexpressing the edited GluA2αR in the adar2MO restored normal expressions of cresting and sox9b. Moreover, overexpressing the unedited GluA2αQ in the wild type embryos resulted in reduction of crestin and sox9b expressions. These results argue that an elevated GluA2αQ level is sufficient for generating the

Myosin heavy chain expression in cranial, pectoral fin, and tail muscle regions of zebrafish embryos.

Science.gov (United States)

Peng, Mou-Yun; Wen, Hui-Ju; Shih, Li-Jane; Kuo, Ching-Ming; Hwang, Sheng-Ping L

2002-12-01

To investigate whether different myosin heavy chain (MHC) isoforms may constitute myofibrils in the trunk and tail musculature and if their respective expression may be regulated by spadetail (spt) and no tail (brachyury), we identified and characterized mRNA expression patterns of an embryonic- and tail muscle-specific MHC gene (named myhz2) during zebrafish development in wild type, spt, and ntl mutant embryos. The identified myhz2 MHC gene encodes a polypeptide containing 1,935 amino acids. Deduced amino acid comparisons showed that myhz2 MHC shared 92.6% sequence identity with that of carp fast skeletal MHC. Temporal and spatial myhz2 MHC mRNA expression patterns were analyzed by quantitative RT-PCR and whole-mount in situ hybridization using primer pairs and probes designed from the 3'-untranslated region (UTR). Temporally myhz2 MHC mRNA appears in pharyngula embryos and peaks in protruding-mouth larvae. The expression level decreased in 7-day-old hatching larvae, and mRNA expression was not detectable in adult fish. Spatially in pharyngula embryos, mRNA was localized only in the tail somite region, while in long-pec embryos, transcripts were also expressed in the two cranial muscle elements of the adductor mandibulae and medial rectus, as well as in pectoral fin muscles and the tail muscle region. Myhz2 MHC mRNA was expressed in most cranial muscle elements, pectoral fin muscles, and the tail muscle region of 3-day-old hatching larvae. In contrast, no expression of myhz2 MHC mRNA could be observed in spt prim-15 mutant embryos. In spt long-pec mutant embryos, transcripts were expressed in two cranial muscle elements and the tail muscle region, but not in pectoral fin muscles, while only trace amounts of myhz2 MHC mRNA were expressed in the remaining tail muscle region of 38 hpf and long-pec ntl mutant embryos. Copyright 2002 Wiley-Liss, Inc.

Protostrongylid parasites and pneumonia in captive and wild thinhorn sheep (Ovis dalli).

Science.gov (United States)

Jenkins, E J; Veitch, A M; Kutz, S J; Bollinger, T K; Chirino-Trejo, J M; Elkin, B T; West, K H; Hoberg, E P; Polley, L

2007-04-01

We describe health significance of protostrongylid parasites (Parelaphostrongylus odocoilei and Protostrongylus stilesi) and other respiratory pathogens in more than 50 naturally infected Dall's sheep (Ovis dalli dalli) from the Mackenzie Mountains, Northwest Territories (1998-2002) as well as in three Stone's sheep (O. d. stonei) experimentally infected with P. odocoilei (2000-2002). Histological lesions in the brain and distribution of P. odocoilei in the muscles of experimentally and naturally infected sheep were consistent with a previously hypothesized "central nervous system to muscle" pattern of migration for P. odocoilei. Dimensions of granulomas associated with eggs of P. odocoilei and density of protostrongylid eggs and larvae in the cranial lung correlated with intensity of larvae in feces, and all varied with season of collection. Prevalence of P. stilesi based on the presence of larvae in feces underestimated true prevalence (based on examination of lungs) in wild Dall's sheep collected in summer and fall. Similarly, counts of both types of protostrongylid larvae in feces were unreliable indicators of parasitic infection in wild Dall's sheep with concomitant bacterial pneumonia associated with Arcanobacterium pyogenes, Pasteurella sp., and Mannheimia sp. Diffuse, interstitial pneumonia due to P. odocoilei led to fatal pulmonary hemorrhage and edema after exertion in one experimentally infected Stone's sheep and one naturally infected Dall's sheep. Bacterial and verminous pneumonia associated with pathogens endemic in wild Dall's sheep in the Mackenzie Mountains caused sporadic mortalities. There was no evidence of respiratory viruses or bacterial strains associated with domestic ruminants, from which this population of wild sheep has been historically isolated.

Multiple Cranial Nerve Involvement In Cryptococcal Meningitis

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Mahadevan A; Kumar A; Santosh V; Satishchandra P; Shankar S.K

2000-01-01

Cryptococcal meningitis is an uncommon cause of multiple cranial nerve palsies. This case report illustrates one such case of cryptococcal meningitis clinically manifesting with extensive cranial nerve involvement in an HIV seronegative individual. Histology revealed infiltration of the cranial nerves by cryptococci causing axonal disruption with secondary demyelination in the absence of any evidence of inflammation or vasculitis. We believe that axonal damage underlies the pathogenesis of...

Spontaneous generation of rapidly transmissible prions in transgenic mice expressing wild-type bank vole prion protein.

Science.gov (United States)

Watts, Joel C; Giles, Kurt; Stöhr, Jan; Oehler, Abby; Bhardwaj, Sumita; Grillo, Sunny K; Patel, Smita; DeArmond, Stephen J; Prusiner, Stanley B

2012-02-28

Currently, there are no animal models of the most common human prion disorder, sporadic Creutzfeldt-Jakob disease (CJD), in which prions are formed spontaneously from wild-type (WT) prion protein (PrP). Interestingly, bank voles (BV) exhibit an unprecedented promiscuity for diverse prion isolates, arguing that bank vole PrP (BVPrP) may be inherently prone to adopting misfolded conformations. Therefore, we constructed transgenic (Tg) mice expressing WT BVPrP. Tg(BVPrP) mice developed spontaneous CNS dysfunction between 108 and 340 d of age and recapitulated the hallmarks of prion disease, including spongiform degeneration, pronounced astrogliosis, and deposition of alternatively folded PrP in the brain. Brain homogenates of ill Tg(BVPrP) mice transmitted disease to Tg(BVPrP) mice in ∼35 d, to Tg mice overexpressing mouse PrP in under 100 d, and to WT mice in ∼185 d. Our studies demonstrate experimentally that WT PrP can spontaneously form infectious prions in vivo. Thus, Tg(BVPrP) mice may be useful for studying the spontaneous formation of prions, and thus may provide insight into the etiology of sporadic CJD.

Dose selenomethionine have radio-protective effect on cell lines with wild type p53?

International Nuclear Information System (INIS)

Tsuji, K.; Hagihira, T.; Ohnishi, K.; Ohnishi, T.; Matsumoto, H.

2003-01-01

Full text: Selenium compounds are known to have cancer preventive effects. It is reported recently that selenium in the form of selenomethionine (SeMet) can protect cells with wild type p53 from UV-induced cell killing by activating the DNA repair mechanism of p53 tumor suppressor protein via redox factor Ref1 by reducing p53 cysteine residue 275 and 277. In contrast, SeMet has no protective effect on UV-induced cell killing in p53-null cells. If SeMet also has protective effect in cells with wild type p53 on cell killing by photon irradiation, SeMet can be used as normal tissue radio-protector. We examined the effect of SeMet on cell killing by X-ray irradiation in several cell lines with different p53 status at exponentially growing phase. Cell lines used in this experiment were as follows: H1299/neo; human lung cancer cell line of p53 null type tranfected with control vector with no p53, H1299/wp53; wild type p53 transfected counterpart. A172/neo; human glioblastoma cell line with wild type p53, A172/mp53-248; mp53-248 (248-mutant, ARG >TRP) transfected counterpart. SAS/neo; human tongue cancer cell line with wild type p53, and SAS/mp53-248; mp53-248 transfected counterpart. Cells were subcultured at monolayer in D-MEM containing 10% FBS. Survivals of the cells were determined by colony forming ability. Ten-MV linac X-ray was used to irradiate the cells. Exponentially growing cells were incubated with 20μM of SeMet for 15 hours before irradiation. After 24 hours exposure of SeMet, cells were incubated up to two weeks in growth medium for colony formation. Twenty-four hours exposure of 20μM of SeMet had no cytotoxicity on these cell lines. SeMet had no modification effect on cell killing by photon irradiation in H1299/neo, H1299/wp53, SAS/neo, SAS/mp53-248, and A172/mp53-248. On the other hand, SeMet sensitized A172/neo in radiation cell killing. The effects of p53 on interaction of SeMet and photon irradiation differ according to cell lines

ELECTROPHORETIC MOBILITIES OF ESCHERICHIA COLI 0157:H7 AND WILD-TYPE ESCHERICHIA COLI STRAINS

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The electrophoretic mobility (EPM) of a number of human-virulent and "wild-type" Escherichia coli strains in phosphate buffered water was measured. The impact of pH, ionic strength, cation type (valence) and concentration, and bacterial strain on the EPM was investigated. Resul...

Differential radiodiagnosis of cranial lesions in hyperparathyroid and deforming asteodystrophy, fibrous osteoplasia, multiple myeloma and tumor metastases to the cranial bones

International Nuclear Information System (INIS)

Spuzyak, M.I.

1986-01-01

The results of an analysis of craniographic findings were provided for 58 patients with primary hyperparathyrosis, 12 with fibrous osteodysplasia, 6 with deforming osteodystrophy, 14 with multiple myeloma and 16 with tumor metastases to the cranial bones. A study was made of some features of roentgenological semiotics (changes in the structure thickness and shapes of the cranial bones) of cranial bone lesions in the above diseases. Differential radiodiagnosis of cranial lesions in hypeparathyroid and deforming osteodystrophy, fibrous osteodysplasia, multiple myeloma and metastatic lesions of the cranial bones should be based not on single signs but on the symptom-complex (x-ray syndrome). For each of the analysed diseases x-ray syndromes were described

Anthelmintic effect of Psidium guajava and Tagetes erecta on wild-type and Levamisole-resistant Caenorhabditis elegans strains.

Science.gov (United States)

Piña-Vázquez, Denia M; Mayoral-Peña, Zyanya; Gómez-Sánchez, Maricela; Salazar-Olivo, Luis A; Arellano-Carbajal, Fausto

2017-04-18

Psidium guajava and Tagetes erecta have been used traditionally to treat gastrointestinal parasites, but their active metabolites and mechanisms of action remain largely unknown. To evaluate the anthelmintic potential of Psidium guajava and Tagetes erecta extracts on Levamisole-sensitive and Levamisole-resistant strains of the model nematode Caenorhabditis elegans. Aqueous extracts of Psidium guajava (PGE) and Tagetes erecta (TEE) were assayed on locomotion and egg-laying behaviors of the wild-type (N2) and Levamisole-resistant (CB193) strains of Caenorhabditis elegans. Both extracts paralyzed wild-type and Levamisole-resistant nematodes in a dose-dependent manner. In wild-type worms, TEE 25mg/mL induced a 75% paralysis after 8h of treatment and PGE 25mg/mL induced a 100% paralysis after 4h of treatment. PGE exerted a similar paralyzing effect on N2 wild-type and CB193 Levamisole-resistant worms, while TEE only partially paralyzed CB193 worms. TEE 25mg/mL decreased N2 egg-laying by 65% with respect to the untreated control, while PGE did it by 40%. Psidium guajava leaves and Tagetes erecta flower-heads possess hydrosoluble compounds that block the motility of Caenorhabditis elegans by a mechanism different to that of the anthelmintic drug Levamisole. Effects are also observable on oviposition, which was diminished in the wild-type worms. The strong anthelmintic effects in crude extracts of these plants warrants future work to identify their active compounds and to elucidate their molecular mechanisms of action. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Caffeine Abolishes the Ultraviolet-Induced REV3 Translesion Replication Pathway in Mouse Cells

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Kouichi Yamada

2011-11-01

Full Text Available When a replicative DNA polymerase stalls upon encountering a photoproduct on the template strand, it is relieved by other low-processivity polymerase(s, which insert nucleotide(s opposite the lesion. Using an alkaline sucrose density gradient sedimentation technique, we previously classified this process termed UV-induced translesion replication (UV-TLS into two types. In human cancer cells or xeroderma pigmentosum variant (XP-V cells, UV-TLS was inhibited by caffeine or proteasome inhibitors. However, in normal human cells, the process was insensitive to these reagents. Reportedly, in yeast or mammalian cells, REV3 protein (a catalytic subunit of DNA polymerase ζ is predominantly involved in the former type of TLS. Here, we studied UV-TLS in fibroblasts derived from the Rev3-knockout mouse embryo (Rev3KO-MEF. In the wild-type MEF, UV-TLS was slow (similar to that of human cancer cells or XP-V cells, and was abolished by caffeine or MG-262. In 2 cell lines of Rev3KO-MEF (Rev3−/− p53−/−, UV-TLS was not observed. In p53KO-MEF, which is a strict control for Rev3KO-MEF, the UV-TLS response was similar to that of the wild-type. Introduction of the Rev3 expression plasmid into Rev3KO-MEF restored the UV-TLS response in selected stable transformants. In some transformants, viability to UV was the same as that in the wild-type, and the death rate was increased by caffeine. Our findings indicate that REV3 is predominantly involved in UV-TLS in mouse cells, and that the REV3 translesion pathway is suppressed by caffeine or proteasome inhibitors.

21 CFR 882.4360 - Electric cranial drill motor.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Electric cranial drill motor. 882.4360 Section 882...) MEDICAL DEVICES NEUROLOGICAL DEVICES Neurological Surgical Devices § 882.4360 Electric cranial drill motor. (a) Identification. An electric cranial drill motor is an electrically operated power source used...

Skeletal muscle fibrosis in the mdx/utrn+/- mouse validates its suitability as a murine model of Duchenne muscular dystrophy.

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Gutpell, Kelly M; Hrinivich, William T; Hoffman, Lisa M

2015-01-01

Various therapeutic approaches have been studied for the treatment of Duchenne muscular dystrophy (DMD), but none of these approaches have led to significant long-term effects in patients. One reason for this observed inefficacy may be the use of inappropriate animal models for the testing of therapeutic agents. The mdx mouse is the most widely used murine model of DMD, yet it does not model the fibrotic progression observed in patients. Other murine models of DMD are available that lack one or both alleles of utrophin, a functional analog of dystrophin. The aim of this study was to compare fibrosis and myofiber damage in the mdx, mdx/utrn+/- and double knockout (dko) mouse models. We used Masson's trichrome stain and percentage of centrally-nucleated myofibers as indicators of fibrosis and myofiber regeneration, respectively, to assess disease progression in diaphragm and gastrocnemius muscles harvested from young and aged wild-type, mdx, mdx/utrn+/- and dko mice. Our results indicated that eight week-old gastrocnemius muscles of both mdx/utrn+/- and dko hind limb developed fibrosis whereas age-matched mdx gastrocnemius muscle did not (p = 0.002). The amount of collagen found in the mdx/utrn+/- diaphragm was significantly higher than that found in the corresponding diaphragm muscles of wild-type animals, but not of mdx animals (p = 0.0003). Aged mdx/utrn+/- mice developed fibrosis in both diaphragm and gastrocnemius muscles compared to wild-type controls (p = 0.003). Mdx diaphragm was fibrotic in aged mice as well (p = 0.0235), whereas the gastrocnemius muscle in these animals was not fibrotic. We did not measure a significant difference in collagen staining between wild-type and mdx gastrocnemius muscles. The results of this study support previous reports that the moderately-affected mdx/utrn+/- mouse is a better model of DMD, and we show here that this difference is apparent by 2 months of age.

Twelfth cranial nerve involvement in Guillian Barre syndrome.

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Nanda, Subrat Kumar; Jayalakshmi, Sita; Ruikar, Devashish; Surath, Mohandas

2013-07-01

Guillian Barre Syndrome (GBS) is associated with cranial nerve involvement. Commonest cranial nerves involved were the facial and bulbar (IXth and Xth). Involvement of twelfth cranial nerve is rare in GBS. We present a case of GBS in a thirteen years old boy who developed severe tongue weakness and wasting at two weeks after the onset of GBS. The wasting and weakness of tongue improved at three months of follow up. Brief review of the literature about XIIth cranial nerve involvement in GBS is discussed.

Twelfth cranial nerve involvement in Guillian Barre syndrome

OpenAIRE

Subrat Kumar Nanda; Sita Jayalakshmi; Devashish Ruikar; Mohandas Surath

2013-01-01

Guillian Barre Syndrome (GBS) is associated with cranial nerve involvement. Commonest cranial nerves involved were the facial and bulbar (IXth and Xth). Involvement of twelfth cranial nerve is rare in GBS. We present a case of GBS in a thirteen years old boy who developed severe tongue weakness and wasting at two weeks after the onset of GBS. The wasting and weakness of tongue improved at three months of follow up. Brief review of the literature about XIIth cranial nerve involvement in GBS is...

Cranial MR finding of reversible eclampsia

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Sohn, Seok Ho; Hwang, Mi Young; Kim, Kyu Hwa; Kim, Seon Goo; Lee, Sung Moon; Kim, Hong; Joo, Yang Goo; Suh, Soo Ji [College of Medicine, Keimyung University, Daegu (Korea, Republic of)

1994-05-15

To evaluate clinical usefulness of cranial magnetic resonance imaging(MRI) in diagnosis and for follow-up of reversible eclampsia. Cranial MRI was performed on four consecutive pregnant patients(ante-partum 3 cases, postpartum 1 cases), who had generalized tonic-clonic seizure caused by eclampsia. One of the four patients underwent follow-up MRI. Cranial MRI typically demonstrated bilateral hyperintense lesions on T2-weighted images and iso-to hypointense lesions on T1-weighted images. MRI abnormalities were most commonly located in the distribution of the posterior cerebral artery circulation and were associated with symptoms of visual disturbance. Most cranial lesions of eclampsia demonstrated in MRI were reversible. MRI with its capability to detect even subtle abnormalities in the brain that are not visible on CT, and may be the technique of choice for evaluating the cerebral the pathology of pregnant women with eclampsia.

Cranial base pathology in pediatric osteogenesis imperfecta patients treated with bisphosphonates.

Science.gov (United States)

Arponen, Heidi; Vuorimies, Ilkka; Haukka, Jari; Valta, Helena; Waltimo-Sirén, Janna; Mäkitie, Outi

2015-03-01

Cranial base pathology is a serious complication of osteogenesis imperfecta (OI). Our aim was to analyze whether bisphosphonate treatment, used to improve bone strength, could also prevent the development of craniocervical junction pathology (basilar impression, basilar invagination, or platybasia) in children with OI. In this single-center retrospective study the authors analyzed the skull base morphology from lateral skull radiographs and midsagittal MR images (total of 94 images), obtained between the ages of 0 and 25 years in 39 bisphosphonate-treated OI patients. The results were compared with age-matched normative values and with findings in 70 OI patients who were not treated with bisphosphonates. In addition to cross-sectional data, longitudinal data were available from 22 patients with an average follow-up period of 7.6 years. The patients, who had OI types I, III, IV, VI, and VII, had been treated with zoledronic acid, pamidronate, or risedronate for 3.2 years on average. Altogether 33% of the 39 bisphosphonate-treated patients had at least 1 cranial base anomaly, platybasia being the most prevalent diagnosis (28%). Logistic regression analysis suggested a higher risk of basilar impression or invagination in patients with severe OI (OR 22.04) and/or older age at initiation of bisphosphonate treatment (OR 1.45), whereas a decreased risk was associated with longer duration of treatment (OR 0.28). No significant associations between age, height, or cumulative bisphosphonate dose and the risk for cranial base anomaly were detected. In longitudinal evaluation, Kaplan-Meier curves suggested delayed development of cranial base pathology in patients treated with bisphosphonates but the differences from the untreated group were not statistically significant. These findings indicate that cranial base pathology may develop despite bisphosphonate treatment. Early initiation of bisphosphonate treatment may delay development of craniocervical junction pathology

Comparison of the nucleotide sequence of wild-type hepatitis - A virus and its attenuated candidate vaccine derivative

International Nuclear Information System (INIS)

Cohen, J.I.; Rosenblum, B.; Ticehurst, J.R.; Daemer, R.; Feinstone, S.; Purcell, R.H.

1987-01-01

Development of attenuated mutants for use as vaccines is in progress for other viruses, including influenza, rotavirus, varicella-zoster, cytomegalovirus, and hepatitis-A virus (HAV). Attenuated viruses may be derived from naturally occurring mutants that infect human or nonhuman hosts. Alternatively, attenuated mutants may be generated by passage of wild-type virus in cell culture. Production of attenuated viruses in cell culture is a laborious and empiric process. Despite previous empiric successes, understanding the molecular basis for attenuation of vaccine viruses could facilitate future development and use of live-virus vaccines. Comparison of the complete nucleotide sequences of wild-type (virulent) and vaccine (attenuated) viruses has been reported for polioviruses and yellow fever virus. Here, the authors compare the nucleotide sequence of wild-type HAV HM-175 with that of a candidate vaccine derivative

Common themes and cell type specific variations of higher order chromatin arrangements in the mouse

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Cremer Thomas

2005-12-01

Full Text Available Abstract Background Similarities as well as differences in higher order chromatin arrangements of human cell types were previously reported. For an evolutionary comparison, we now studied the arrangements of chromosome territories and centromere regions in six mouse cell types (lymphocytes, embryonic stem cells, macrophages, fibroblasts, myoblasts and myotubes with fluorescence in situ hybridization and confocal laser scanning microscopy. Both species evolved pronounced differences in karyotypes after their last common ancestors lived about 87 million years ago and thus seem particularly suited to elucidate common and cell type specific themes of higher order chromatin arrangements in mammals. Results All mouse cell types showed non-random correlations of radial chromosome territory positions with gene density as well as with chromosome size. The distribution of chromosome territories and pericentromeric heterochromatin changed during differentiation, leading to distinct cell type specific distribution patterns. We exclude a strict dependence of these differences on nuclear shape. Positional differences in mouse cell nuclei were less pronounced compared to human cell nuclei in agreement with smaller differences in chromosome size and gene density. Notably, the position of chromosome territories relative to each other was very variable. Conclusion Chromosome territory arrangements according to chromosome size and gene density provide common, evolutionary conserved themes in both, human and mouse cell types. Our findings are incompatible with a previously reported model of parental genome separation.

Piper betle induces phase I & II genes through Nrf2/ARE signaling pathway in mouse embryonic fibroblasts derived from wild type and Nrf2 knockout cells.

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Wan Hasan, Wan Nuraini; Kwak, Mi-Kyoung; Makpol, Suzana; Wan Ngah, Wan Zurinah; Mohd Yusof, Yasmin Anum

2014-02-23

Nuclear factor-erythroid 2 p45 related factor 2 (Nrf2) is a primary transcription factor, protecting cells from oxidative stress by regulating a number of antioxidants and phase II detoxifying enzymes. Dietary components such as sulforaphane in broccoli and quercetin in onions have been shown to be inducers of Nrf2. Piper betle (PB) grows well in tropical climate and the leaves are used in a number of traditional remedies for the treatment of stomach ailments and infections among Asians. The aim of this study was to elucidate the effect of Piper betle (PB) leaves extract in Nrf2 signaling pathway by using 2 types of cells; mouse embryonic fibroblasts (MEFs) derived from wild-type (WT) and Nrf2 knockout (N0) mice. WT and N0 cells were treated with 5 and 10 μg/ml of PB for 10 and 12-h for the determination of nuclear translocation of Nrf2 protein. Luciferase reporter gene activity was performed to evaluate the antioxidant response element (ARE)-induction by PB. Real-time PCR and Western blot were conducted on both WT and N0 cells after PB treatment for the determination of antioxidant enzymes [superoxide dismutase (SOD1) and heme-oxygenase (HO-1)], phase I oxidoreductase enzymes [ quinone oxidoreductase (NQO1)] and phase II detoxifying enzyme [glutathione S-transferase (GST)]. Nuclear translocation of Nrf2 by PB in WT cells was better after 10 h incubation compared to 12 h. Real time PCR and Western blot analysis showed increased expressions of Nrf2, NQO1 and GSTA1 genes with corresponding increases in glutathione, NQO1 and HO-1 proteins in WT cells. Reporter gene ARE was stimulated by PB as shown by ARE/luciferase assay. Interestingly, PB induced SOD1 gene and protein expressions in N0 cells but not in WT cells. The results of this study confirmed that PB activated Nrf2-ARE signaling pathway which subsequently induced some phase I oxidoreductase, phase II detoxifying and antioxidant genes expression via ARE reporter gene involved in the Nrf2 pathway with the

Twelfth cranial nerve involvement in Guillian Barre syndrome

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Subrat Kumar Nanda

2013-01-01

Full Text Available Guillian Barre Syndrome (GBS is associated with cranial nerve involvement. Commonest cranial nerves involved were the facial and bulbar (IXth and Xth. Involvement of twelfth cranial nerve is rare in GBS. We present a case of GBS in a thirteen years old boy who developed severe tongue weakness and wasting at two weeks after the onset of GBS. The wasting and weakness of tongue improved at three months of follow up. Brief review of the literature about XIIth cranial nerve involvement in GBS is discussed.

Cranial nerves - spectrum of inflammatory and tumorous changes

International Nuclear Information System (INIS)

Nemec, S.F.; Kasprian, G.; Nemec, U.; Czerny, C.

2009-01-01

Inflammatory processes as well as primary and secondary tumorous changes may involve cranial nerves causing neurological deficits. In addition to neurologists, ENT physicians, ophthalmologists and maxillofacial surgeons, radiologists play an important role in the investigation of patients with cranial nerve symptoms. Multidetector computed tomography (MDCT) and particularly magnetic resonance imaging (MRI) allow the depiction of the cranial nerve anatomy and pathological neural changes. This article briefly describes the imaging techniques in MDCT and MRI and is dedicated to the radiological presentation of inflammatory and tumorous cranial nerve pathologies. (orig.) [de

Craniomandibular form and body size variation of first generation mouse hybrids: A model for hominin hybridization.

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Warren, Kerryn A; Ritzman, Terrence B; Humphreys, Robyn A; Percival, Christopher J; Hallgrímsson, Benedikt; Ackermann, Rebecca Rogers

2018-03-01

Hybridization occurs in a number of mammalian lineages, including among primate taxa. Analyses of ancient genomes have shown that hybridization between our lineage and other archaic hominins in Eurasia occurred numerous times in the past. However, we still have limited empirical data on what a hybrid skeleton looks like, or how to spot patterns of hybridization among fossils for which there are no genetic data. Here we use experimental mouse models to supplement previous studies of primates. We characterize size and shape variation in the cranium and mandible of three wild-derived inbred mouse strains and their first generation (F 1 ) hybrids. The three parent taxa in our analysis represent lineages that diverged over approximately the same period as the human/Neanderthal/Denisovan lineages and their hybrids are variably successful in the wild. Comparisons of body size, as quantified by long bone measurements, are also presented to determine whether the identified phenotypic effects of hybridization are localized to the cranium or represent overall body size changes. The results indicate that hybrid cranial and mandibular sizes, as well as limb length, exceed that of the parent taxa in all cases. All three F 1 hybrid crosses display similar patterns of size and form variation. These results are generally consistent with earlier studies on primates and other mammals, suggesting that the effects of hybridization may be similar across very different scenarios of hybridization, including different levels of hybrid fitness. This paper serves to supplement previous studies aimed at identifying F 1 hybrids in the fossil record and to introduce further research that will explore hybrid morphologies using mice as a proxy for better understanding hybridization in the hominin fossil record. Copyright © 2017 Elsevier Ltd. All rights reserved.

Secular trends in Cherokee cranial morphology: Eastern vs Western bands.

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Sutphin, Rebecca; Ross, Ann H; Jantz, Richard L

2014-01-01

The research objective was to examine if secular trends can be identified for cranial data commissioned by Boas in 1892, specifically for cranial breadth and cranial length of the Eastern and Western band Cherokee who experienced environmental hardships. Multiple regression analysis was used to test the degree of relationship between each of the cranial measures: cranial length, cranial breadth and cephalic index, along with predictor variables (year-of-birth, location, sex, admixture); the model revealed a significant difference for all craniometric variables. Additional regression analysis was performed with smoothing Loess plots to observe cranial length and cranial breadth change over time (year-of-birth) separately for Eastern and Western Cherokee band females and males born between 1783-1874. This revealed the Western and Eastern bands show a decrease in cranial length over time. Eastern band individuals maintain a relatively constant head breadth, while Western Band individuals show a sharp decline beginning around 1860. These findings support negative secular trend occurring for both Cherokee bands where the environment made a detrimental impact; this is especially marked with the Western Cherokee band.

Establishment and characterization of a hypocatalasemic mouse cell strain

International Nuclear Information System (INIS)

Utsumi, Hiroshi; Tano, Keizo; Hashimoto, Mitsumasa W.; Kodama, Seiji; Watanabe, Hiromitsu

1998-01-01

Contact-inhibited catalase-deficient fibroblast cell strain has been established from the homozygous hypocatalasemic C3H/Cs b mutant mouse. This cell strain has low level of catalase enzyme activity and has normal level of enzyme activities of both glutathione peroxidase and superoxide dismutase. Catalase-deficient C3H/Cs b mutant cell strain is markedly more sensitive to the toxicity of hydrogen peroxide compared to wild-type C3H/Cs a cell strain. In addition, mutant cell strain is sensitive to X-rays and near-UV compared to wild-type cell strain, but shows the same sensitivities to topoisomerase II inhibitors, adriamycin and 4'-(9-acridinylamino) methanesulfon-m-anisidide (m-AMSA), and the DNA cross-linking agents, cis-diamminedichloroplatinum (II) (cis-Pt) and trans-diamminedichloroplatinum (II) (trans-Pt). These cell strains will be of use in the study of the roles which catalase plays in the intracellular prevention of DNA damage induced by oxidative stress. (author)

Metabolism of styrene to styrene oxide and vinylphenols in cytochrome P450 2F2- and P450 2E1-knockout mouse liver and lung microsomes.

Science.gov (United States)

Shen, Shuijie; Li, Lei; Ding, Xinxin; Zheng, Jiang

2014-01-21

Pulmonary toxicity of styrene is initiated by cytochromes P450-dependent metabolic activation. P450 2E1 and P450 2F2 are considered to be two main cytochrome P450 enzymes responsible for styrene metabolism in mice. The objective of the current study was to determine the correlation between the formation of styrene metabolites (i.e., styrene oxide and 4-vinylphenol) and pulmonary toxicity of styrene, using Cyp2e1- and Cyp2f2-null mouse models. A dramatic decrease in the formation of styrene glycol and 4-vinylphenol was found in Cyp2f2-null mouse lung microsomes relative to that in the wild-type mouse lung microsomes; however, no significant difference in the production of the styrene metabolites was observed between lung microsomes obtained from Cyp2e1-null and the wild-type mice. The knockout and wild-type mice were treated with styrene (6.0 mmol/kg, ip), and cell counts and LDH activity in bronchoalveolar lavage fluids were monitored to evaluate the pulmonary toxicity induced by styrene. Cyp2e1-null mice displayed a susceptibility to lung toxicity of styrene similar to that of the wild-type animals; however, Cyp2f2-null mice were resistant to styrene-induced pulmonary toxicity. In conclusion, both P450 2E1 and P450 2F2 are responsible for the metabolic activation of styrene. The latter enzyme plays an important role in styrene-induced pulmonary toxicity. Both styrene oxide and 4-vinylphenol are suggested to participate in the development of lung injury induced by styrene.

The naming of the cranial nerves: a historical review.

Science.gov (United States)

Davis, Matthew C; Griessenauer, Christoph J; Bosmia, Anand N; Tubbs, R Shane; Shoja, Mohammadali M

2014-01-01

The giants of medicine and anatomy have each left their mark on the history of the cranial nerves, and much of the history of anatomic study can be viewed through the lens of how the cranial nerves were identified and named. A comprehensive literature review on the classification of the cranial names was performed. The identification of the cranial nerves began with Galen in the 2nd century AD and evolved up through the mid-20th century. In 1778, Samuel Sömmerring, a German anatomist, classified the 12 cranial nerves as we recognize them today. This review expands on the excellent investigations of Flamm, Shaw, and Simon et al., with discussion of the historical identification as well as the process of naming the human cranial nerves. Copyright © 2013 Wiley Periodicals, Inc.

Original Research. Correlation Between Cranial Base Morphology And Various Types Of Skeletal Anomalies

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Panainte Irinel

2017-03-01

Full Text Available Background: Previous studies regarding various types of malocclusions have found correlations between the angle of the base of the skull and prognathism. Aim of the study: This cephalometric study sought to investigate the function of the cranium base angle in different types of malocclusion on a group of Romanian subjects. Materials and methods: Forty-four cephalometric radiographs were selected from patients referred to orthodontic treatment. The cephalometric records were digitized, and with the CorelDRAW Graphics Suite X5 software 22 landmarks have been marked on each radiograph. A number of linear and angular variables were calculated. Results: The angle of the base of the skull was found to be higher in Class II Division 1 subjects compared to the Class I group. The cranial base lengths, N-S and S-Ba, were significantly larger in both categories of Class II malocclusion than in Class I patients, but measurements were comparable in Class I and Class III. The SNA angle showed no considerable variation between Class I subjects and the other groups. SNA-SNP was significantly increased above Class I values in Class II Division1 and Class II Division 2 groups. No significant dissimilarities were observed for these lengths between Class I and Class III patients. Conclusions: The angle of the cranium base (S-N-Ba, S-N-Ar does not have a major role in the progression of malocclusion. In Angle Class II malocclusion the SNA angle is increased, and SNB is increased in malocclusion Class III. The anterior skull base length is increased in Class II anomalies. The length of the maxillary bone base is increased in Class II malocclusions type; in Class III type of malocclusion the length of the mandible bone is increased.

The fusion protein of wild-type canine distemper virus is a major determinant of persistent infection

International Nuclear Information System (INIS)

Plattet, Philippe; Rivals, Jean-Paul; Zuber, BenoIt; Brunner, Jean-Marc; Zurbriggen, Andreas; Wittek, Riccardo

2005-01-01

The wild-type A75/17 canine distemper virus (CDV) strain induces a persistent infection in the central nervous system but infects cell lines very inefficiently. In contrast, the genetically more distant Onderstepoort CDV vaccine strain (OP-CDV) induces extensive syncytia formation. Here, we investigated the roles of wild-type fusion (F WT ) and attachment (H WT ) proteins in Vero cells expressing, or not, the canine SLAM receptor by transfection experiments and by studying recombinants viruses expressing different combinations of wild-type and OP-CDV glycoproteins. We show that low fusogenicity is not due to a defect of the envelope proteins to reach the cell surface and that H WT determines persistent infection in a receptor-dependent manner, emphasizing the role of SLAM as a potent enhancer of fusogenicity. However, importantly, F WT reduced cell-to-cell fusion independently of the cell surface receptor, thus demonstrating that the fusion protein of the neurovirulent A75/17-CDV strain plays a key role in determining persistent infection

O6-methylguanine-DNA methyltransferase in wild-type and ada mutants of Escherichia coli

International Nuclear Information System (INIS)

Mitra, S.; Pal, B.C.; Foote, R.S.

1982-01-01

O 6 -Methylguanine-DNA methyltransferase is induced in Escherichia coli during growth in low levels of N-methyl-N'-nitro-N-nitrosoguanidine. We have developed a sensitive assay for quantitating low levels of this activity with a synthetic DNA substrate containing 3 H-labeled O 6 -methylguanine as the only modified base. Although both wild-type and adaptation-deficient (ada) mutants of E. coli contained low but comparable numbers (from 13 to 60) of the enzyme molecules per cell, adaptation treatment caused a significant increase of the enzyme in the wild type but not in the ada mutants, suggesting that the ada mutation is in a regulatory locus and not in the structural gene for the methyltransferase

Evaluation of an animation tool developed to supplement dental student study of the cranial nerves.

Science.gov (United States)

Lone, M; McKenna, J P; Cryan, J F; Vagg, T; Toulouse, A; Downer, E J

2017-12-30

The structure/function of the cranial nerves is a core topic for dental students. However, due to the perceived complexity of the subject, it is often difficult for students to develop a comprehensive understanding of key concepts using textbooks and models. It is accepted that the acquisition of anatomical knowledge can be facilitated by visualisation of structures. This study aimed to develop and assess a novel cranial nerve animation as a supplemental learning aid for dental students. A multidisciplinary team of anatomists, neuroscientists and a computer scientist developed a novel animation depicting the cranial nerves. The animation was viewed by newly enrolled first-year dental students, graduate entry dental students (year 1) and dental hygiene students (year 1). A simple life scenario employing the use of the cranial nerves was developed using a cartoon-type animation with a viewing time of 3.58 minutes. The animation was developed with emphasis on a life scenario. The animation was placed online for 2 weeks with open access or viewed once in a controlled laboratory setting. Questionnaires were designed to assess the participants' attitude towards the animation and their knowledge of the cranial nerves before and after visualisation. This study was performed before the delivery of core lectures on the cranial nerves. Our findings indicate that the use of the animation can act as a supplemental tool to improve student knowledge of the cranial nerves. Indeed, data indicate that a single viewing of the animation, in addition to 2-week access to the animation, can act as a supplemental learning tool to assist student understanding of the structure and function of cranial nerves. The animation significantly enhanced the student's opinion that their cranial nerve knowledge had improved. From a qualitative point of view, the students described the animation as an enjoyable and useful supplement to reading material/lectures and indicated that the animation was a

Expression of wild-type and mutant medium-chain acyl-CoA dehydrogenase (MCAD) cDNA in eucaryotic cells

DEFF Research Database (Denmark)

Jensen, T G; Andresen, B S; Bross, P

1992-01-01

An effective EBV-based expression system for eucaryotic cells has been developed and used for the study of the mitochondrial enzyme medium-chain acyl-CoA dehydrogenase (MCAD). 1325 bp of PCR-generated MCAD cDNA, containing the entire coding region, was placed between the SV40 early promoter...... and polyadenylation signals in the EBV-based vector. Both wild-type MCAD cDNA and cDNA containing the prevalent disease-causing mutation A to G at position 985 of the MCAD cDNA were tested. In transfected COS-7 cells, the steady state amount of mutant MCAD protein was consistently lower than the amount of wild......-type human enzyme. The enzyme activity in extracts from cells harbouring the wild-type MCAD cDNA was dramatically higher than in the controls (harbouring the vector without the MCAD gene) while only a slightly higher activity was measured with the mutant MCAD. The mutant MCAD present behaves like wild...

The correlation between the use of personal protective equipment and level wild-type p53 of dental technicians in Surabaya

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Puspa Dila Rohmaniar

2017-03-01

Full Text Available Background: Exposure of metals among dental technicians that come from the working environment can lead to the formation reactive oxygen species (ROS. ROS can cause mutations in the p53 gene (p53. The mutation is transversion mutation GuanineThymine. p53 mutations can lead to low expression of the wild-type p53 protein (p53. Wild-type p53 involved in many biological processes such as regulation of genes involved in cell cycle, cell growth after DNA damage, and apoptosis. However, exposure to metals among dental technicians can be prevented through the use of personal protective equipment (PPE during work. Purpose: The purpose of this study was to analyze the correlation between the use of personal protective equipment to wild-type p53 protein levels among dental technicians in Surabaya. Method: This study was observational analytic with cross sectional approach. 40 samples were taken by random sampling. Data were retrieved through interviews and observations. Wild-type p53 was analyzed from saliva with indirect ELISA method. Analysis of data used Kolmogorov Smirnov normality test and a Pearson correlation test. Value significance was p<0.05 (95% confidence level. Result: There was a significant association between the use of personal protective equipment with wild-type p53 levels with p=0.002 Conclusion: The use PPE properly is positively correlated with the wild-type p53 protein levels of dental technicians in Surabaya.

Enhanced Wnt signaling improves bone mass and strength, but not brittleness, in the Col1a1(+/mov13) mouse model of type I Osteogenesis Imperfecta.

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Jacobsen, Christina M; Schwartz, Marissa A; Roberts, Heather J; Lim, Kyung-Eun; Spevak, Lyudmila; Boskey, Adele L; Zurakowski, David; Robling, Alexander G; Warman, Matthew L

2016-09-01

Osteogenesis Imperfecta (OI) comprises a group of genetic skeletal fragility disorders. The mildest form of OI, Osteogenesis Imperfecta type I, is frequently caused by haploinsufficiency mutations in COL1A1, the gene encoding the α1(I) chain of type 1 collagen. Children with OI type I have a 95-fold higher fracture rate compared to unaffected children. Therapies for OI type I in the pediatric population are limited to anti-catabolic agents. In adults with osteoporosis, anabolic therapies that enhance Wnt signaling in bone improve bone mass, and ongoing clinical trials are determining if these therapies also reduce fracture risk. We performed a proof-of-principle experiment in mice to determine whether enhancing Wnt signaling in bone could benefit children with OI type I. We crossed a mouse model of OI type I (Col1a1(+/Mov13)) with a high bone mass (HBM) mouse (Lrp5(+/p.A214V)) that has increased bone strength from enhanced Wnt signaling. Offspring that inherited the OI and HBM alleles had higher bone mass and strength than mice that inherited the OI allele alone. However, OI+HBM and OI mice still had bones with lower ductility compared to wild-type mice. We conclude that enhancing Wnt signaling does not make OI bone normal, but does improve bone properties that could reduce fracture risk. Therefore, agents that enhance Wnt signaling are likely to benefit children and adults with OI type 1. Copyright © 2016 Elsevier Inc. All rights reserved.

Effect of uremia on HDL composition, vascular inflammation, and atherosclerosis in wild-type mice

DEFF Research Database (Denmark)

Bang, Christian A; Bro, Susanne; Bartels, Emil D

2007-01-01

Wild-type mice normally do not develop atherosclerosis, unless fed cholic acid. Uremia is proinflammatory and increases atherosclerosis 6- to 10-fold in apolipoprotein E-deficient mice. This study examined the effect of uremia on lipoproteins, vascular inflammation, and atherosclerosis in wild...... in cholic acid-fed sham mice. The results suggest that moderate uremia neither induces aortic inflammation nor atherosclerosis in C57BL/6J mice despite increased LDL/HDL cholesterol ratio and altered HDL composition....

High-dose radiation-induced meningioma following prophylactic cranial irradiation for acute lymphoblastic leukaemia

International Nuclear Information System (INIS)

Matsuda, Ryosuke; Nikaido, Yuji; Yamada, Tomonori; Mishima, Hideaki; Tamaki, Ryo

2005-01-01

A 12 year-old girl was treated with prophylactic cranial irradiation for acute lymphoblastic leukaemia (ALL). At the age of 39, she was admitted to our hospital for status epilepticus. Computed tomography demonstrated two, enhancing bilateral sided intracranial tumors. After surgery, this patient presented meningiomas which histologically, were of the meningothelial type. The high cure rate in childhood ALL, attributable to aggressive chemotherapy and prophylactic cranial irradiation, is capable of inducing secondary brain tumor. Twelve cases of high-dose radiation-induced meningioma following ALL are also reviewed. (author)

High-dose radiation-induced meningioma following prophylactic cranial irradiation for acute lymphoblastic leukaemia

Energy Technology Data Exchange (ETDEWEB)

Matsuda, Ryosuke; Nikaido, Yuji; Yamada, Tomonori; Mishima, Hideaki; Tamaki, Ryo [National Hospital Organization Osaka Minami Medical Center, Kawachinagano (Japan)

2005-03-01

A 12 year-old girl was treated with prophylactic cranial irradiation for acute lymphoblastic leukaemia (ALL). At the age of 39, she was admitted to our hospital for status epilepticus. Computed tomography demonstrated two, enhancing bilateral sided intracranial tumors. After surgery, this patient presented meningiomas which histologically, were of the meningothelial type. The high cure rate in childhood ALL, attributable to aggressive chemotherapy and prophylactic cranial irradiation, is capable of inducing secondary brain tumor. Twelve cases of high-dose radiation-induced meningioma following ALL are also reviewed. (author)

Epizootiology of cranial abscess disease in white-tailed deer (Odocoileus virginianus) of Georgia, USA

Science.gov (United States)

Cohen, Bradley S.; Belser, Emily H.; Killmaster, Charlie H.; Bowers, John W.; Irwin, Brian J.; Yabsley, Michael J.; Miller, Karl V.

2015-01-01

Intracranial abscess disease is a cause of natural mortality for mature male white-tailed deer (Odocoileus virginianus). Most cases of abscesses are associated with bacterial infection byTrueperella (Arcanobacterium) pyogenes, but a complete understanding of the epidemiology of this disease is lacking. We quantified the effects of individual characteristics, site-specific herd demographics, land cover, and soil variables in estimating the probability of this disease. We examined 7,545 white-tailed deer from 60 sites throughout Georgia US for signs of cranial abscesses, the predecessor of intracranial abscesses, and recorded the presence or absence of cranial abscesses for each individual examined. We detected no cranial abscesses in 2,562 female deer but 91 abscesses in 4,983 male deer examined (1.8%). A generalized linear mixed model, treating site as a random effect, was used to examine several potential explanatory risk factors including site-level landscape and soil characteristics (soil and forest type), demographic factors (deer density and male to female ratio), and individual host factors (deer sex and age). Model results indicated that the probability of a male having a cranial abscess increased with age and that adult sex ratio (male:female) was positively associated with this disease. Site-specific variables for land cover and soil types were not strongly associated with observations of the disease at the scale measured and a large amount of among-site variability remained. Given the demonstrated effect of age, gender, and local sex ratios but the remaining unexplained spatial variability, additional investigation into spatiotemporal variation of the presumed bacterial causative agent of cranial abscesses appears warranted.

CT measurments of cranial growth: normal subjects

International Nuclear Information System (INIS)

Hahn, F.J.; Chu, W.K.; Cheung, J.Y.

1984-01-01

Growth patterns of the cranium measured directly as head circumference have been well documented. With the availability of computed tomography (CT) , cranial dimensions can be obtained easily. The objective of this project was to establish the mean values and their normal variance of CT cranial area of subjects at different ages. Cranial area and its long and short axes were measured on CT scans for 215 neurologic patients of a wide age range who presented no evidence of abnormal growth of head size. Growth patterns of the cranial area as well as the numeric product of it linear dimensions were determined via a curve fitting process. The patterns resemble that of the head circumference growth chart, with the most rapid growth observed in the first 12 months of age and reaching full size during adolescence

Wild-type minimal inhibitory concentration distributions in bacteria of animal origin in Argentina

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Florencia L Pantozzi

Full Text Available The aim of this study was to determine the antimicrobial resistance profiles of indicator bacteria isolated from domestic animal feces. Minimal inhibitory concentration (MIC was determined by agar dilution. Interpretative criteria on the basis of wild-type MIC distributions and epidemiological cutoff values (ECOFF or ECV were used according to the 'European Committee on Antimicrobial Susceptibility Testing' (EUCAST data. Results from 237 isolates of Escherichia coli showed reduced susceptibility for ampicillin, streptomycin and tetracycline, the antimicrobials commonly used in intensive breeding of pigs and hens. Regarding all the species of the genus Enterococcus spp., there are only ECOFF or ECV for vancomycin. Of the 173 Enterococcus spp. isolated, only one showed reduced susceptibility to vancomycin and was classified as 'non-wild-type' (NWT population. This is the first report in Argentina showing data of epidemiological cutoff values in animal bacteria.

Schwannoma originating from lower cranial nerves: report of 4 cases.

Science.gov (United States)

Oyama, Hirofumi; Kito, Akira; Maki, Hideki; Hattori, Kenichi; Noda, Tomoyuki; Wada, Kentaro

2012-02-01

Four cases of schwannoma originating from the lower cranial nerves are presented. Case 1 is a schwannoma of the vagus nerve in the parapharyngeal space. The operation was performed by the transcervical approach. Although the tumor capsule was not dissected from the vagus nerve, hoarseness and dysphagia happened transiently after the operation. Case 2 is a schwannoma in the jugular foramen. The operation was performed by the infralabyrinthine approach. Although only the intracapsular tumor was enucleated, facial palsy, hoarseness, dysphagia and paresis of the deltoid muscle occurred transiently after the operation. The patient's hearing had also slightly deteriorated. Case 3 is a dumbbell-typed schwannoma originating from the hypoglossal nerve. The hypoglossal canal was markedly enlarged by the tumor. As the hypoglossal nerves were embedded in the tumor, the tumor around the hypoglossal nerves was not resected. The tumor was significantly enlarged for a while after stereotactic irradiation. Case 4 is an intracranial cystic schwannoma originating from the IXth or Xth cranial nerves. The tumor was resected through the cerebello-medullary fissure. The tumor capsule attached to the brain stem was not removed. Hoarseness and dysphagia happened transiently after the operation. Cranial nerve palsy readily occurs after the removal of the schwannoma originating from the lower cranial nerves. Mechanical injury caused by retraction, extension and compression of the nerve and heat injury during the drilling of the petrous bone should be cautiously avoided.

A cerebellar learning model of vestibulo-ocular reflex adaptation in wild-type and mutant mice.

Science.gov (United States)

Clopath, Claudia; Badura, Aleksandra; De Zeeuw, Chris I; Brunel, Nicolas

2014-05-21

Mechanisms of cerebellar motor learning are still poorly understood. The standard Marr-Albus-Ito theory posits that learning involves plasticity at the parallel fiber to Purkinje cell synapses under control of the climbing fiber input, which provides an error signal as in classical supervised learning paradigms. However, a growing body of evidence challenges this theory, in that additional sites of plasticity appear to contribute to motor adaptation. Here, we consider phase-reversal training of the vestibulo-ocular reflex (VOR), a simple form of motor learning for which a large body of experimental data is available in wild-type and mutant mice, in which the excitability of granule cells or inhibition of Purkinje cells was affected in a cell-specific fashion. We present novel electrophysiological recordings of Purkinje cell activity measured in naive wild-type mice subjected to this VOR adaptation task. We then introduce a minimal model that consists of learning at the parallel fibers to Purkinje cells with the help of the climbing fibers. Although the minimal model reproduces the behavior of the wild-type animals and is analytically tractable, it fails at reproducing the behavior of mutant mice and the electrophysiology data. Therefore, we build a detailed model involving plasticity at the parallel fibers to Purkinje cells' synapse guided by climbing fibers, feedforward inhibition of Purkinje cells, and plasticity at the mossy fiber to vestibular nuclei neuron synapse. The detailed model reproduces both the behavioral and electrophysiological data of both the wild-type and mutant mice and allows for experimentally testable predictions. Copyright © 2014 the authors 0270-6474/14/347203-13$15.00/0.

Motor palsies of cranial nerves (excluding VII) after vaccination: reports to the US Vaccine Adverse Event Reporting System.

Science.gov (United States)

Woo, Emily Jane; Winiecki, Scott K; Ou, Alan C

2014-01-01

We reviewed cranial nerve palsies, other than VII, that have been reported to the US Vaccine Adverse Event Reporting System (VAERS). We examined patterns for differences in vaccine types, seriousness, age, and clinical characteristics. We identified 68 reports of cranial nerve palsies, most commonly involving the oculomotor (III), trochlear (IV), and abducens (VI) nerves. Isolated cranial nerve palsies, as well as palsies occurring as part of a broader clinical entity, were reported. Forty reports (59%) were classified as serious, suggesting that a cranial nerve palsy may sometimes be the harbinger of a broader and more ominous clinical entity, such as a stroke or encephalomyelitis. There was no conspicuous clustering of live vs. inactivated vaccines. The patient age range spanned the spectrum from infants to the elderly. Independent data may help to clarify whether, when, and to what extent the rates of cranial nerve palsies following particular vaccines may exceed background levels.

Glycomic analyses of mouse models of congenital muscular dystrophy.

Science.gov (United States)

Stalnaker, Stephanie H; Aoki, Kazuhiro; Lim, Jae-Min; Porterfield, Mindy; Liu, Mian; Satz, Jakob S; Buskirk, Sean; Xiong, Yufang; Zhang, Peng; Campbell, Kevin P; Hu, Huaiyu; Live, David; Tiemeyer, Michael; Wells, Lance

2011-06-17

Dystroglycanopathies are a subset of congenital muscular dystrophies wherein α-dystroglycan (α-DG) is hypoglycosylated. α-DG is an extensively O-glycosylated extracellular matrix-binding protein and a key component of the dystrophin-glycoprotein complex. Previous studies have shown α-DG to be post-translationally modified by both O-GalNAc- and O-mannose-initiated glycan structures. Mutations in defined or putative glycosyltransferase genes involved in O-mannosylation are associated with a loss of ligand-binding activity of α-DG and are causal for various forms of congenital muscular dystrophy. In this study, we sought to perform glycomic analysis on brain O-linked glycan structures released from proteins of three different knock-out mouse models associated with O-mannosylation (POMGnT1, LARGE (Myd), and DAG1(-/-)). Using mass spectrometry approaches, we were able to identify nine O-mannose-initiated and 25 O-GalNAc-initiated glycan structures in wild-type littermate control mouse brains. Through our analysis, we were able to confirm that POMGnT1 is essential for the extension of all observed O-mannose glycan structures with β1,2-linked GlcNAc. Loss of LARGE expression in the Myd mouse had no observable effect on the O-mannose-initiated glycan structures characterized here. Interestingly, we also determined that similar amounts of O-mannose-initiated glycan structures are present on brain proteins from α-DG-lacking mice (DAG1) compared with wild-type mice, indicating that there must be additional proteins that are O-mannosylated in the mammalian brain. Our findings illustrate that classical β1,2-elongation and β1,6-GlcNAc branching of O-mannose glycan structures are dependent upon the POMGnT1 enzyme and that O-mannosylation is not limited solely to α-DG in the brain.

Cranial radiation in childhood acute lymphocytic leukemia. Neuropsychologic sequelae

International Nuclear Information System (INIS)

Whitt, J.K.; Wells, R.J.; Lauria, M.M.; Wilhelm, C.L.; McMillan, C.W.

1984-01-01

A battery of neuropsychologic tests was administered ''blindly'' to 18 children with acute lymphocytic leukemia (ALL) who had been randomly assigned to treatment regimens with or without cranial radiation. These children were all in complete continuous remission for more than 3 1/2 years and were no longer receiving therapy. The results indicated no substantial differences between groups as a function of radiation therapy. However, decreased neuropsychologic performance was found when the entire sample was compared with population norms. These data do not support the hypothesis that cranial radiation therapy is responsible for the neuropsychologic sequelae seen in these survivors of ALL. Post hoc multiple regression analysis indicated that parental education levels accounted for more of the neuropsychologic variability seen in these children than other factors such as age at diagnosis, type of therapy, or sex of child

The anatomic surgical arterial segmentation of the kidney in wild boar (Sus scrofa

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Elizângela Falcão Vale

2006-12-01

Full Text Available Thirty pairs of kidneys of wild boar (Sus scrofa were studied from adult males, with permission from the Brazilian Institute of the Environment (Process nº 02001.003237/05, aiming to characterize the vasculature and anatomic surgical segmentation. The arteries of these kidneys were injected with red pigment and subsequently submitted to acid corrosion in order to identify the renal arterial vascular pattern, particularly its divisions and distribution. The results reveal the sectorial branches of the renal arteries, two in number (cranial and caudal; the sectorial arteries provide the segmentary branches to the dorsal and ventral portions of the kidney; in the right kidney, the segmentary branches are 2-6 in the cranial sector and 3-7 in the caudal sector. In the right kidney, the segmentary branches are 3-7 and 2-7 in the same respective sectors; the vascular arterial symmetry (25% between the right and left kidney in the animals is evident. There are 3 arterial anatomic surgical segments on both kidneys. On the basis of the distribution of the sectorial and segmentary arteries, it is possible to accomplish setorectomy and segmentectomy on the kidneys of the wild boar, with functional aspects such as species preservation and animal experimental modeling.

Overexpression of dimethylarginine dimethylaminohydrolase 1 attenuates airway inflammation in a mouse model of asthma.

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Kayla G Kinker

Full Text Available Levels of asymmetric dimethylarginine (ADMA, an endogenous inhibitor of nitric oxide synthase, are increased in lung, sputum, exhaled breath condensate and plasma samples from asthma patients. ADMA is metabolized primarily by dimethylarginine dimethylaminohydrolase 1 (DDAH1 and DDAH2. We determined the effect of DDAH1 overexpression on development of allergic inflammation in a mouse model of asthma. The expression of DDAH1 and DDAH2 in mouse lungs was determined by RT-quantitative PCR (qPCR. ADMA levels in bronchoalveolar lavage fluid (BALF and serum samples were determined by mass spectrometry. Wild type and DDAH1-transgenic mice were intratracheally challenged with PBS or house dust mite (HDM. Airway inflammation was assessed by bronchoalveolar lavage (BAL total and differential cell counts. The levels of IgE and IgG1 in BALF and serum samples were determined by ELISA. Gene expression in lungs was determined by RNA-Seq and RT-qPCR. Our data showed that the expression of DDAH1 and DDAH2 was decreased in the lungs of mice following HDM exposure, which correlated with increased ADMA levels in BALF and serum. Transgenic overexpression of DDAH1 resulted in decreased BAL total cell and eosinophil numbers following HDM exposure. Total IgE levels in BALF and serum were decreased in HDM-exposed DDAH1-transgenic mice compared to HDM-exposed wild type mice. RNA-Seq results showed downregulation of genes in the inducible nitric oxide synthase (iNOS signaling pathway in PBS-treated DDAH1-transgenic mice versus PBS-treated wild type mice and downregulation of genes in IL-13/FOXA2 signaling pathway in HDM-treated DDAH1-transgenic mice versus HDM-treated wild type mice. Our findings suggest that decreased expression of DDAH1 and DDAH2 in the lungs may contribute to allergic asthma and overexpression of DDAH1 attenuates allergen-induced airway inflammation through modulation of Th2 responses.

Morphometry and acetylcholinesterase activity of the myenteric plexus of the wild mouse Calomys callosus

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L.B.M. Maifrino

1997-05-01

Full Text Available The myenteric plexus of the digestive tract of the wild mouse Calomys callosus was examined using a histochemical method that selectively stains nerve cells, and the acetylcholinesterase (AChE histochemical technique in whole-mount preparations. Neuronal density was 1,500 ± 116 neurons/cm2 (mean ± SEM in the esophagus, 8,900 ± 1,518 in the stomach, 9,000 ± 711 in the jejunum and 13,100 ± 2,089 in the colon. The difference in neuronal density between the esophagus and other regions was statistically significant. The neuron profile area ranged from 45 to 1,100 µm2. The difference in nerve cell size between the jejunum and other regions was statistically significant. AChE-positive nerve fibers were distributed within the myenteric plexus which is formed by a primary meshwork of large nerve bundles and a secondary meshwork of finer nerve bundles. Most of the nerve cells displayed AChE activity in the cytoplasm of different reaction intensities. These results are important in order to understand the changes occurring in the myenteric plexus in experimental Chagas' disease

The evolution of cerebellar tonsillar herniation after cranial vault remodeling surgery.

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Leikola, J; Hukki, A; Karppinen, A; Valanne, L; Koljonen, V

2012-10-01

We sought to examine the pre- and postoperative changes of cerebellar tonsillar herniation by MR imaging in asymptomatic pediatric patients with nonsyndromic, single-suture craniosynostosis (N-SSSC), who underwent cranial vault remodeling surgery without suboccipital decompression. We required cerebellar tonsillar herniation through foramen magnum ≥3 mm for Chiari type I malformation (CMI). We hypothesized that the increase of intracranial volume by cranial vault remodeling would correct the asymptomatic CMI. We identified 9 patients among 121 N-SSSC children undergoing craniofacial surgery from January 2004 to October 2010 with CMI. However, two of them were excluded from the study due to missing postoperative MR images. In the final study population, six were males, five were scaphocephalic, while two were diagnosed with coronal synostosis. In four of the cases, the CMI was decreased in postoperative MR imaging varying from 6 to 12 mm. In three cases, the herniation remained stable. The median change of cerebellar tonsillar herniation was -6.5 mm. We conclude that asymptomatic patients with existing CMI may benefit from cranial vault remodeling surgery alone increasing the intracranial volume.

An investigation into the regulation of intra-cranial pressure and its influence upon the surrounding cranial bones.

Science.gov (United States)

Gard, Graham

2009-07-01

The aim of this study is to present a rational coherent hypothesis to explain the palpable involuntary movements of the cranium. The arterial and venous anatomy inside and around the skull and spinal column presents a complete vascular system with the capacity to regulate intra-cranial pressure to a level of equilibrium slightly higher than atmospheric pressure. Variations in cerebrospinal fluid (csf) pressure control the volume of blood draining through the cavernous sinus and hence into the inter-vertebral venous plexus in relation to the jugular vein. Stable intra-cranial pressure is maintained by a controlled release of venous blood through the inter-vertebral venous plexus (slow) and the jugular vein (fast) in the cavernous sinus. Any distortion of the skull from its healthy state will lead to reduced intra-cranial volume. The process of release from the state of compression has been interpreted as "cranial rhythm" but may be a mechanical adjustment increasing the internal volume of the skull, aided by the continual maintenance of stable intracranial pressure. This involuntary movement is capable of being assisted manually.

Bone tissue ultrastructural defects in a mouse model for osteogenesis imperfecta: a Raman spectroscopy study

Science.gov (United States)

Chen, Tsoching; Kozloff, Kenneth M.; Goldstein, Steven A.; Morris, Michael D.

2004-07-01

Osteogenesis imperfecta (OI) is genetic defect in which the genes that code for the α1(I) or α2(I) chains of type I collagen are defective. The defects often result in substitution of a bulky amino acid for glycine, causing formation of collagen that can not form the normal triple helix. Depending on the details of the defects, the outcomes range from controllable to lethal. This study focuses on OI type IV, a more common and moderately severe form of the disease. People with the disease have a substantial increase in the risk and rate of fracture. We examine the spectroscopic consequences of these defects, using a mouse model (BRTL) that mimics OI type IV. We compare Raman images from tibial cortical tissue of wild-type mice and BRTL mice with single copy of mutation and show that both mineral to matrix ratios and collagen inter-fibril cross-links are different in wild-type and mutant mice.

[From anatomy to image: the cranial nerves at MRI].

Science.gov (United States)

Conforti, Renata; Marrone, Valeria; Sardaro, Angela; Faella, Pierluigi; Grassi, Roberta; Cappabianca, Salvatore

2013-01-01

In this article, we review the expected course of each of the 12 cranial nerves. Traditional magnetic resonance imaging depicts only the larger cranial nerves but SSFP sequences of magnetic resonance imaging are capable of depicting the cisternal segments of 12 cranial nerves and also provide submillimetric spatial resolution.

Infant Positioning, Baby Gear Use, and Cranial Asymmetry.

Science.gov (United States)

Zachry, Anne H; Nolan, Vikki G; Hand, Sarah B; Klemm, Susan A

2017-12-01

Objectives This study aimed to identify predictors of cranial asymmetry. We hypothesize that among infants diagnosed with cranial asymmetry in the sampled region, there is an association between exposure to more time in baby gear and less awake time in prone and side-lying than in infants who do not present with this condition. Methods The study employed a cross sectional survey of caregivers of typically developing infants and infants diagnosed with cranial asymmetry. Results A mutivariable model reveals that caregivers of children who are diagnosed with cranial asymmetry report their children spending significantly less time in prone play than those children without a diagnosis of cranial asymmetry. Side-lying and time spent in baby gear did not attain statistical significance. Conclusions for Practice Occupational therapists, physical therapists, pediatricians, nurses and other health care professionals must provide parents with early education about the importance of varying positions and prone play in infancy and address fears and concerns that may serve as barriers to providing prone playtime.

Wild-Type, but Not Mutant N296H, Human Tau Restores Aβ-Mediated Inhibition of LTP in Tau−/− mice

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Mariana Vargas-Caballero

2017-04-01

Full Text Available Microtubule associated protein tau (MAPT is involved in the pathogenesis of Alzheimer's disease and many forms of frontotemporal dementia (FTD. We recently reported that Aβ-mediated inhibition of hippocampal long-term potentiation (LTP in mice requires tau. Here, we asked whether expression of human MAPT can restore Aβ-mediated inhibition on a mouse Tau−/− background and whether human tau with an FTD-causing mutation (N296H can interfere with Aβ-mediated inhibition of LTP. We used transgenic mouse lines each expressing the full human MAPT locus using bacterial artificial chromosome technology. These lines expressed all six human tau protein isoforms on a Tau−/− background. We found that the human wild-type MAPT H1 locus was able to restore Aβ42-mediated impairment of LTP. In contrast, Aβ42 did not reduce LTP in slices in two independently generated transgenic lines expressing tau protein with the mutation N296H associated with frontotemporal dementia (FTD. Basal phosphorylation of tau measured as the ratio of AT8/Tau5 immunoreactivity was significantly reduced in N296H mutant hippocampal slices. Our data show that human MAPT is able to restore Aβ42-mediated inhibition of LTP in Tau−/− mice. These results provide further evidence that tau protein is central to Aβ-induced LTP impairment and provide a valuable tool for further analysis of the links between Aβ, human tau and impairment of synaptic function.

Cranial joint histology in the mallard duck (Anas platyrhynchos): new insights on avian cranial kinesis.

Science.gov (United States)

Bailleul, Alida M; Witmer, Lawrence M; Holliday, Casey M

2017-03-01

The evolution of avian cranial kinesis is a phenomenon in part responsible for the remarkable diversity of avian feeding adaptations observable today. Although osteological, developmental and behavioral features of the feeding system are frequently studied, comparatively little is known about cranial joint skeletal tissue composition and morphology from a microscopic perspective. These data are key to understanding the developmental, biomechanical and evolutionary underpinnings of kinesis. Therefore, here we investigated joint microstructure in juvenile and adult mallard ducks (Anas platyrhynchos; Anseriformes). Ducks belong to a diverse clade of galloanseriform birds, have derived adaptations for herbivory and kinesis, and are model organisms in developmental biology. Thus, new insights into their cranial functional morphology will refine our understanding of avian cranial evolution. A total of five specimens (two ducklings and three adults) were histologically sampled, and two additional specimens (a duckling and an adult) were subjected to micro-computed tomographic scanning. Five intracranial joints were sampled: the jaw joint (quadrate-articular); otic joint (quadrate-squamosal); palatobasal joint (parasphenoid-pterygoid); the mandibular symphysis (dentary-dentary); and the craniofacial hinge (a complex flexion zone involving four different pairs of skeletal elements). In both the ducklings and adults, the jaw, otic and palatobasal joints are all synovial, with a synovial cavity and articular cartilage on each surface (i.e. bichondral joints) ensheathed in a fibrous capsule. The craniofacial hinge begins as an ensemble of patent sutures in the duckling, but in the adult it becomes more complex: laterally it is synovial; whereas medially, it is synostosed by a bridge of chondroid bone. We hypothesize that it is chondroid bone that provides some of the flexible properties of this joint. The heavily innervated mandibular symphysis is already fused in the

Comparison of clastogen-induced gene expression profiles in wild-type and DNA repair-deficient Rad54/Rad54B cells

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van Benthem Jan

2010-01-01

Full Text Available Abstract Background Previously we found that Rad54/Rad54B cells are more sensitive towards mitomycin C (MMC as compared to wild-type (WT cells. This difference in sensitivity was absent upon exposure to other clastogens like bleomycin (BLM and γ-radiation. In order to get further insight into possible underlying mechanisms, gene expression changes in WT and Rad54/Rad54B MEFs (mouse embryonic fibroblasts after exposure to the clastogens MMC and BLM were investigated. Exposures of these cells to mutagens (N-ac-AAF and ENU and vehicle were taken as controls. Results Most exposures resulted in an induction of DNA damage signaling and apoptosis genes and a reduced expression of cell division genes in cells of both genotypes. As expected, responses to N-ac-AAF were very similar in both genotypes. ENU exposure did not lead to significant gene expression changes in cells of both genotypes, presumably due to its short half-life. Gene expression responses to clastogens, however, showed a genotype-dependent effect for BLM and MMC. MMC treated Rad54/Rad54B MEFs showed no induction of p53-signaling, DNA damage response and apoptosis as seen for all the other treatments. Conclusion These data support our finding that different types of clastogens exist and that responses to these types depend on the DNA repair status of the cells.

Rho family GTP binding proteins are involved in the regulatory volume decrease process in NIH3T3 mouse fibroblasts

DEFF Research Database (Denmark)

Pedersen, Stine F; Beisner, Kristine H; Willumsen, Berthe M

2002-01-01

The role of Rho GTPases in the regulatory volume decrease (RVD) process following osmotic cell swelling is controversial and has so far only been investigated for the swelling-activated Cl- efflux. We investigated the involvement of RhoA in the RVD process in NIH3T3 mouse fibroblasts, using wild......-type cells and three clones expressing constitutively active RhoA (RhoAV14). RhoAV14 expression resulted in an up to fourfold increase in the rate of RVD, measured by large-angle light scattering. The increase in RVD rate correlated with RhoAV14 expression. RVD in wild-type cells was unaffected by the Rho...

Differences in ultrasonic vocalizations between wild and laboratory California mice (Peromyscus californicus.

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Matina C Kalcounis-Rueppell

Full Text Available BACKGROUND: Ultrasonic vocalizations (USVs emitted by muroid rodents, including laboratory mice and rats, are used as phenotypic markers in behavioral assays and biomedical research. Interpretation of these USVs depends on understanding the significance of USV production by rodents in the wild. However, there has never been a study of muroid rodent ultrasound function in the wild and comparisons of USVs produced by wild and laboratory rodents are lacking to date. Here, we report the first comparison of wild and captive rodent USVs recorded from the same species, Peromyscus californicus. METHODOLOGY AND PRINCIPAL FINDINGS: We used standard ultrasound recording techniques to measure USVs from California mice in the laboratory (Peromyscus Genetic Stock Center, SC, USA and the wild (Hastings Natural History Reserve, CA, USA. To determine which California mouse in the wild was vocalizing, we used a remote sensing method that used a 12-microphone acoustic localization array coupled with automated radio telemetry of all resident Peromyscus californicus in the area of the acoustic localization array. California mice in the laboratory and the wild produced the same types of USV motifs. However, wild California mice produced USVs that were 2-8 kHz higher in median frequency and significantly more variable in frequency than laboratory California mice. SIGNIFICANCE: The similarity in overall form of USVs from wild and laboratory California mice demonstrates that production of USVs by captive Peromyscus is not an artifact of captivity. Our study validates the widespread use of USVs in laboratory rodents as behavioral indicators but highlights that particular characteristics of laboratory USVs may not reflect natural conditions.

Molecular cloning and tissue-specific expression analysis of mouse spinesin, a type II transmembrane serine protease 5

International Nuclear Information System (INIS)

Watanabe, Yoshihisa; Okui, Akira; Mitsui, Shinichi; Kawarabuki, Kentaro; Yamaguchi, Tatsuyuki; Uemura, Hidetoshi; Yamaguchi, Nozomi

2004-01-01

We have previously reported novel serine proteases isolated from cDNA libraries of the human and mouse central nervous system (CNS) by PCR using degenerate oligodeoxyribonucleotide primers designed on the basis of the serine protease motifs, AAHC and DSGGP. Here we report a newly isolated serine protease from the mouse CNS. This protease is homologous (77.9% identical) to human spinesin type II transmembrane serine protease 5. Mouse spinesin (m-spinesin) is also composed of (from the N-terminus) a short cytoplasmic domain, a transmembrane domain, a stem region containing a scavenger-receptor-like domain, and a serine protease domain, as is h-spinesin. We also isolated type 1, type 2, and type 3 variant cDNAs of m-spinesin. Full-length spinesin (type 4) and type 3 contain all the domains, whereas type 1 and type 2 variants lack the cytoplasmic, transmembrane, and scavenger-receptor-like domains. Subcellular localization of the variant forms was analyzed using enhanced green fluorescent protein (EGFP) fusion proteins. EGFP-type 4 fusion protein was predominantly localized to the ER, Golgi apparatus, and plasma membrane, whereas EGFP-type 1 was localized to the cytoplasm, reflecting differential classification of m-spinesin variants into transmembrane and cytoplasmic types. We analyzed the distribution of m-spinesin variants in mouse tissues, using RT-PCR with variant-specific primer sets. Interestingly, transmembrane-type spinesin, types 3 and 4, was specifically expressed in the spinal cord, whereas cytoplasmic type, type 1, was expressed in multiple tissues, including the cerebrum and cerebellum. Therefore, m-spinesin variants may have distinct biological functions arising from organ-specific variant expression

Aberrant regeneration of the third cranial nerve.

Science.gov (United States)

Shrestha, U D; Adhikari, S

2012-01-01

Aberrant regeneration of the third cranial nerve is most commonly due to its damage by trauma. A ten-month old child presented with the history of a fall from a four-storey building. She developed traumatic third nerve palsy and eventually the clinical features of aberrant regeneration of the third cranial nerve. The adduction of the eye improved over time. She was advised for patching for the strabismic amblyopia as well. Traumatic third nerve palsy may result in aberrant regeneration of the third cranial nerve. In younger patients, motility of the eye in different gazes may improve over time. © NEPjOPH.

Effect of Osteopathic Cranial Manipulative Medicine on Visual Function.

Science.gov (United States)

Sandhouse, Mark E; Shechtman, Diana; Fecho, Gregory; Timoshkin, Elena M

2016-11-01

The effects of osteopathic cranial manipulative medicine (OCMM) on visual function have been poorly characterized in the literature. Based on a pilot study conducted by their research group, the authors conducted a study that examined whether OCMM produced a measurable change in visual function in adults with cranial asymmetry. Randomized, controlled, double-blinded clinical trial. The intervention and control (sham therapy) were applied during 8 weekly visits, and participants in both groups received 8 weekly follow-up visits. Adult volunteers aged between 18 and 35 years with unremarkable systemic or ocular history were recruited. Inclusion criteria were refractive error between 6 diopters of myopia and 5 diopters of hyperopia, regular astigmatism of any amount, and cranial somatic dysfunction. All participants were evaluated for cranial asymmetry and randomly assigned to the treatment or sham therapy group. The treatment group received OCMM to correct cranial dysfunctions, and the sham therapy group received light pressure applied to the cranium. Preintervention and postintervention ophthalmic examinations consisted of distance visual acuity testing, accommodative system testing, local stereoacuity testing, pupillary size measurements, and vergence system testing. A χ2 analysis was performed to determine participant masking. Analysis of variance was performed for all ophthalmic measures. Eighty-nine participants completed the trial, with 47 in the treatment group and 42 in the sham therapy group. A hierarchical analysis of variance revealed statistically significant within-groups effects (Psize under bright light in the left eye and in near point of convergence break. Osteopathic cranial manipulative medicine may affect visual function in adults with cranial asymmetry. Active motion testing of the cranium for somatic dysfunction may affect the cranial system to a measurable level and explain interrater reliability issues in cranial studies. (Clinical

Interleukin-1 receptor type I gene-deficient mice are less susceptible to Staphylococcus epidermidis biomaterial-associated infection than are wild-type mice

NARCIS (Netherlands)

Boelens, J. J.; van der Poll, T.; Zaat, S. A.; Murk, J. L.; Weening, J. J.; Dankert, J.

2000-01-01

Elevated concentrations of interleukin-1 (IL-1) were found in tissue surrounding biomaterials infected with Staphylococcus epidermidis. To determine the role of IL-1 in biomaterial-associated infection (BAI), IL-1 receptor type I-deficient (IL-1R(-/-)) and wild-type mice received subcutaneous

Cranial imaging in child abuse

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Demaerel, P.; Wilms, G. [Department of Radiology, University Hospitals, Leuven (Belgium); Casteels, I. [Department of Ophthalmology, University Hospitals, Leuven (Belgium)

2002-04-01

Serious head injury in children less than 2 years old is often the result of child abuse. The role of the different neuroimaging modalities in child abuse is reviewed. Skull X-ray and cranial CT are mandatory. Repeat or serial imaging may be necessary and brain MR imaging may contribute to the diagnostic work-up, particularly in the absence of characteristic CT findings. The radiologist plays an important role in accurately identifying non-accidental cranial trauma. The clinical presentation can be non-specific or misleading. The possibility should be considered of a combined mechanism, i.e., an underlying condition with superimposed trauma. In this context, the radiologist is in the front line to suggest the possibility of child abuse. It is therefore important to know the spectrum of, sometimes subtle, imaging findings one may encounter. Opthalmological examination is of the greatest importance and is discussed here, because the combination of retinal hemorrhages and subdural hematoma is very suggestive of non-accidental cranial trauma. (orig.)

Cranial imaging in child abuse

International Nuclear Information System (INIS)

Demaerel, P.; Wilms, G.; Casteels, I.

2002-01-01

Serious head injury in children less than 2 years old is often the result of child abuse. The role of the different neuroimaging modalities in child abuse is reviewed. Skull X-ray and cranial CT are mandatory. Repeat or serial imaging may be necessary and brain MR imaging may contribute to the diagnostic work-up, particularly in the absence of characteristic CT findings. The radiologist plays an important role in accurately identifying non-accidental cranial trauma. The clinical presentation can be non-specific or misleading. The possibility should be considered of a combined mechanism, i.e., an underlying condition with superimposed trauma. In this context, the radiologist is in the front line to suggest the possibility of child abuse. It is therefore important to know the spectrum of, sometimes subtle, imaging findings one may encounter. Opthalmological examination is of the greatest importance and is discussed here, because the combination of retinal hemorrhages and subdural hematoma is very suggestive of non-accidental cranial trauma. (orig.)

Establishment of a mouse model with misregulated chromosome condensation due to defective Mcph1 function.

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Marc Trimborn

Full Text Available Mutations in the human gene MCPH1 cause primary microcephaly associated with a unique cellular phenotype with premature chromosome condensation (PCC in early G2 phase and delayed decondensation post-mitosis (PCC syndrome. The gene encodes the BRCT-domain containing protein microcephalin/BRIT1. Apart from its role in the regulation of chromosome condensation, the protein is involved in the cellular response to DNA damage. We report here on the first mouse model of impaired Mcph1-function. The model was established based on an embryonic stem cell line from BayGenomics (RR0608 containing a gene trap in intron 12 of the Mcph1 gene deleting the C-terminal BRCT-domain of the protein. Although residual wild type allele can be detected by quantitative real-time PCR cell cultures generated from mouse tissues bearing the homozygous gene trap mutation display the cellular phenotype of misregulated chromosome condensation that is characteristic for the human disorder, confirming defective Mcph1 function due to the gene trap mutation. While surprisingly the DNA damage response (formation of repair foci, chromosomal breakage, and G2/M checkpoint function after irradiation appears to be largely normal in cell cultures derived from Mcph1(gt/gt mice, the overall survival rates of the Mcph1(gt/gt animals are significantly reduced compared to wild type and heterozygous mice. However, we could not detect clear signs of premature malignant disease development due to the perturbed Mcph1 function. Moreover, the animals show no obvious physical phenotype and no reduced fertility. Body and brain size are within the range of wild type controls. Gene expression on RNA and protein level did not reveal any specific pattern of differentially regulated genes. To the best of our knowledge this represents the first mammalian transgenic model displaying a defect in mitotic chromosome condensation and is also the first mouse model for impaired Mcph1-function.

Establishment of a mouse model with misregulated chromosome condensation due to defective Mcph1 function.

Science.gov (United States)

Trimborn, Marc; Ghani, Mahdi; Walther, Diego J; Dopatka, Monika; Dutrannoy, Véronique; Busche, Andreas; Meyer, Franziska; Nowak, Stefanie; Nowak, Jean; Zabel, Claus; Klose, Joachim; Esquitino, Veronica; Garshasbi, Masoud; Kuss, Andreas W; Ropers, Hans-Hilger; Mueller, Susanne; Poehlmann, Charlotte; Gavvovidis, Ioannis; Schindler, Detlev; Sperling, Karl; Neitzel, Heidemarie

2010-02-16

Mutations in the human gene MCPH1 cause primary microcephaly associated with a unique cellular phenotype with premature chromosome condensation (PCC) in early G2 phase and delayed decondensation post-mitosis (PCC syndrome). The gene encodes the BRCT-domain containing protein microcephalin/BRIT1. Apart from its role in the regulation of chromosome condensation, the protein is involved in the cellular response to DNA damage. We report here on the first mouse model of impaired Mcph1-function. The model was established based on an embryonic stem cell line from BayGenomics (RR0608) containing a gene trap in intron 12 of the Mcph1 gene deleting the C-terminal BRCT-domain of the protein. Although residual wild type allele can be detected by quantitative real-time PCR cell cultures generated from mouse tissues bearing the homozygous gene trap mutation display the cellular phenotype of misregulated chromosome condensation that is characteristic for the human disorder, confirming defective Mcph1 function due to the gene trap mutation. While surprisingly the DNA damage response (formation of repair foci, chromosomal breakage, and G2/M checkpoint function after irradiation) appears to be largely normal in cell cultures derived from Mcph1(gt/gt) mice, the overall survival rates of the Mcph1(gt/gt) animals are significantly reduced compared to wild type and heterozygous mice. However, we could not detect clear signs of premature malignant disease development due to the perturbed Mcph1 function. Moreover, the animals show no obvious physical phenotype and no reduced fertility. Body and brain size are within the range of wild type controls. Gene expression on RNA and protein level did not reveal any specific pattern of differentially regulated genes. To the best of our knowledge this represents the first mammalian transgenic model displaying a defect in mitotic chromosome condensation and is also the first mouse model for impaired Mcph1-function.

Effects of phorbol ester on mitogen-activated protein kinase kinase activity in wild-type and phorbol ester-resistant EL4 thymoma cells.

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Gause, K C; Homma, M K; Licciardi, K A; Seger, R; Ahn, N G; Peterson, M J; Krebs, E G; Meier, K E

1993-08-05

Phorbol ester-sensitive and -resistant EL4 thymoma cell lines differ in their ability to activate mitogen-activated protein kinase (MAPK) in response to phorbol ester. Treatment of wild-type EL4 cells with phorbol ester results in the rapid activations of MAPK and pp90rsk kinase, a substrate for MAPK, while neither kinase is activated in response to phorbol ester in variant EL4 cells. This study examines the activation of MAPK kinase (MAPKK), an activator of MAPK, in wild-type and variant EL4 cells. Phosphorylation of a 40-kDa substrate, identified as MAPK, was observed following in vitro phosphorylation reactions using cytosolic extracts or Mono Q column fractions prepared from phorbol ester-treated wild-type EL4 cells. MAPKK activity coeluted with a portion of the inactive MAPK upon Mono Q anion-exchange chromatography, permitting detection of the MAPKK activity in fractions containing both kinases. This MAPKK activity was present in phorbol ester-treated wild-type cells, but not in phorbol ester-treated variant cells or in untreated wild-type or variant cells. The MAPKK from wild-type cells was able to activate MAPK prepared from either wild-type or variant cells. MAPKK activity could be stimulated in both wildtype and variant EL4 cells in response to treatment of cells with okadaic acid. These results indicate that the failure of variant EL4 cells to activate MAP kinase in response to phorbol ester is due to a failure to activate MAPKK. Therefore, the step that confers phorbol ester resistance to variant EL4 cells lies between the activation of protein kinase C and the activation of MAPKK.

Cranial mononeuropathy III

Science.gov (United States)

... in the skull. This is one of the cranial nerves that control eye movement. Causes may include: Brain aneurysm Infections Abnormal blood vessels (vascular malformations) Sinus thrombosis Tissue damage from loss of blood flow (infarction) Trauma (from ...

Wild-type and mutated IDH1/2 enzymes and therapy responses.

Science.gov (United States)

Molenaar, Remco J; Maciejewski, Jaroslaw P; Wilmink, Johanna W; van Noorden, Cornelis J F

2018-04-01

Isocitrate dehydrogenase 1 and 2 (IDH1/2) are key enzymes in cellular metabolism, epigenetic regulation, redox states, and DNA repair. IDH1/2 mutations are causal in the development and/or progression of various types of cancer due to supraphysiological production of D-2-hydroxyglutarate. In various tumor types, IDH1/2-mutated cancers predict for improved responses to treatment with irradiation or chemotherapy. The present review discusses the molecular basis of the sensitivity of IDH1/2-mutated cancers with respect to the function of mutated IDH1/2 in cellular processes and their interactions with novel IDH1/2-mutant inhibitors. Finally, lessons learned from IDH1/2 mutations for future clinical applications in IDH1/2 wild-type cancers are discussed.

Distinct types of feeding related neurons in mouse hypothalamus

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Yan eTang

2016-05-01

Full Text Available The last two decades of research provided evidence for a substantial heterogeneity among feeding-related neurons (FRNs in the hypothalamus. However, it remains unclear how FRNs differ in their firing patterns during food intake. Here, we investigated the relationship between the activity of neurons in mouse hypothalamus and their feeding behavior. Using tetrode-based in vivo recording technique, we identified various firing patterns of hypothalamic FRNs, which, after the initiation of food intake, can be sorted into four types: sharp increase (type I, slow increase (type II, sharp decrease (type III and sustained decrease (type IV of firing rates. The feeding-related firing response of FRNs was rigidly related to the duration of food intake and, to a less extent, associated with the type of food. The majority of these FRNs responded to glucose and leptin and exhibited electrophysiological characteristics of putative GABAergic neurons. In conclusion, our study demonstrated the diversity of neurons in the complex hypothalamic network coordinating food intake.

Phase II marker-driven trial of panitumumab and chemotherapy in KRAS wild-type biliary tract cancer

DEFF Research Database (Denmark)

Jensen, L H; Lindebjerg, J; Ploen, J

2012-01-01

BACKGROUND: Combination chemotherapy has proven beneficial in biliary tract cancer and further improvements may be achieved by individualizing treatment based on biomarkers and by adding biological agents. We report the effect of chemotherapy with panitumumab as first-line therapy for KRAS wild....... Combination chemotherapy with panitumumab in patients with KRAS wild-type tumors met the efficacy criteria for future testing in a randomized trial....

[Variation of long-chain 3-hydroxyacyl-CoA dehydrogenase DNA methylation in placenta of different preeclampsia-like mouse models].

Science.gov (United States)

Han, Yiwei; Yang, Zi; Ding, Xiaoyan; Yu, Huan; Yi, Yanhong

2015-10-01

By detecting the variation of long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) DNA methylation in preeclampsia-like mouse models generated by different ways, to explore the roles of multifactor and multiple pathways in preeclampsia pathogenesis on molecular basis. Established preeclampsia-like mouse models in different ways and divided into groups as follows: (1) Nw-nitro-L-arginine-methyl ester (L-NAME) group: wild-type pregnant mouse received subcutaneous injection of L-NAME; (2) lipopolysaccharide (LPS) group: wild-type pregnant mouse received intraperitoneal injection of LPS; (3) apolipoprotein C-III (ApoC3) group: ApoC3 transgenic pregnant mouse with dysregulated lipid metabolism received subcutaneous injection of L-NAME; (4) β2 glycoprotein I (β-2GPI) group: wild-type pregnant mouse received subcutaneous injection of β-2GPI. According to the first injection time (on day 3, 11, 16 respectively), the L-NAME, LPS and ApoC3 groups were further subdivided into: pre-implantation (PI) experimental stage, early gestation (EG) experimental stage, and late gestation (LG) experimental stage. β-2GPI group was only injected before implantation. LCHAD gene methylation levels in placental were detected in different experimental stage. Normal saline control groups were set within wild-type and ApoC3 transgenic pregnant mice simultaneously. (1) CG sites in LCHAD DNA: 45 CG sites were detected in the range of 728 bp before LCHAD gene transcription start site, the 5, 12, 13, 14, 15, 16, 19, 24, 25, 27, 28, 29, 30, 31, 32, 34, 35, 43 CG sites were complex sites which contained two or more CG sequences, others were single site which contained one CG sequence. The 3, 5, 6, 11, 13, 14, 18, 28 sites in L-NAME, LPS, ApoC3 and β-2GPI groups showed different high levels of methylation; the 16, 25, 31, 42, 44 sites showed different low levels of methylation; other 32 sites were unmethylated. (2) Comparison of LCHAD gene methylation between different groups: the methylation levels

Expression of a truncated receptor protein tyrosine phosphatase kappa in the brain of an adult transgenic mouse

DEFF Research Database (Denmark)

Shen, P; Canoll, P D; Sap, J

1999-01-01

that goal, we have used this mouse model to map the distribution of the truncated RPTP-kappa/beta-geo fusion protein in the adult mouse brain using beta-galactosidase as a marker enzyme. Visualization of the beta-galactosidase activity revealed a non-random pattern of expression, and identified cells......-6596]. Nevertheless, since the transgene's expression is driven by the endogenous RPTP-kappa promoter, distribution of the truncated RPTP-kappa/beta-geo fusion protein should reflect the regional and cellular expression of wild-type RPTP-kappa, and thus may identify sites where RPTP-kappa is important. Towards...

Surgical pitfalls with custom-made porous hydroxyapatite cranial implants

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Bruno Zanotti

2015-03-01

Full Text Available Aim: Cranioplasty implants are used primarily in cases of surgical cranial decompression following pathological elevations of intracranial pressure. Available bone substitutes include porous hydroxyapatite (HA and polymethylmethacrylate. Whichever material is used, however, prosthetic cranial implants are susceptible to intra- and postsurgical complications and even failure. The aim of this study was to investigate such occurrences in HA cranioplasty implants, seeking not only to determine the likely causes (whether correlated or not with the device itself but also, where possible, to suggest countermeasures. Methods: We analyzed information regarding failures or complications reported in postmarketing surveillance and clinical studies of patients treated worldwide with custom-made HA cranial implants (Custom Bone Service Fin-Ceramica Faenza, Italy in the period 1997-2013. Results: The two most common complications were implant fractures (84 cases, 2.9% of the total fitted and infections (51 cases, 1.77%. Conclusion: Although cranioplasties are superficial and not difficult types of surgery, and use of custom-made implants are often considered the "easy" option from a surgical perspective, these procedures are nonetheless plagued by potential pitfalls. If performed well they yield more than satisfactory results from the points of view of both the patient and surgeon, but lack of appropriate care can open the door to numerous potential sources of failure, which can compromise-even irreparably-the ability to heal.

Radiation-Induced Alterations in Mouse Brain Development Characterized by Magnetic Resonance Imaging

International Nuclear Information System (INIS)

Gazdzinski, Lisa M.; Cormier, Kyle; Lu, Fred G.; Lerch, Jason P.; Wong, C. Shun; Nieman, Brian J.

2012-01-01

Purpose: The purpose of this study was to identify regions of altered development in the mouse brain after cranial irradiation using longitudinal magnetic resonance imaging (MRI). Methods and Materials: Female C57Bl/6 mice received a whole-brain radiation dose of 7 Gy at an infant-equivalent age of 2.5 weeks. MRI was performed before irradiation and at 3 time points following irradiation. Deformation-based morphometry was used to quantify volume and growth rate changes following irradiation. Results: Widespread developmental deficits were observed in both white and gray matter regions following irradiation. Most of the affected brain regions suffered an initial volume deficit followed by growth at a normal rate, remaining smaller in irradiated brains compared with controls at all time points examined. The one exception was the olfactory bulb, which in addition to an early volume deficit, grew at a slower rate thereafter, resulting in a progressive volume deficit relative to controls. Immunohistochemical assessment revealed demyelination in white matter and loss of neural progenitor cells in the subgranular zone of the dentate gyrus and subventricular zone. Conclusions: MRI can detect regional differences in neuroanatomy and brain growth after whole-brain irradiation in the developing mouse. Developmental deficits in neuroanatomy persist, or even progress, and may serve as useful markers of late effects in mouse models. The high-throughput evaluation of brain development enabled by these methods may allow testing of strategies to mitigate late effects after pediatric cranial irradiation.

Radiation-Induced Alterations in Mouse Brain Development Characterized by Magnetic Resonance Imaging

Energy Technology Data Exchange (ETDEWEB)

Gazdzinski, Lisa M.; Cormier, Kyle [Mouse Imaging Centre, Hospital for Sick Children, Toronto (Canada); Lu, Fred G. [Department of Radiation Oncology, Sunnybrook Health Sciences Centre, Toronto (Canada); Lerch, Jason P. [Mouse Imaging Centre, Hospital for Sick Children, Toronto (Canada); Department of Medical Biophysics, University of Toronto, Toronto (Canada); Wong, C. Shun [Department of Radiation Oncology, Sunnybrook Health Sciences Centre, Toronto (Canada); Department of Medical Biophysics, University of Toronto, Toronto (Canada); Department of Radiation Oncology, University of Toronto, Toronto (Canada); Nieman, Brian J., E-mail: bjnieman@phenogenomics.ca [Mouse Imaging Centre, Hospital for Sick Children, Toronto (Canada); Department of Medical Biophysics, University of Toronto, Toronto (Canada)

2012-12-01

Purpose: The purpose of this study was to identify regions of altered development in the mouse brain after cranial irradiation using longitudinal magnetic resonance imaging (MRI). Methods and Materials: Female C57Bl/6 mice received a whole-brain radiation dose of 7 Gy at an infant-equivalent age of 2.5 weeks. MRI was performed before irradiation and at 3 time points following irradiation. Deformation-based morphometry was used to quantify volume and growth rate changes following irradiation. Results: Widespread developmental deficits were observed in both white and gray matter regions following irradiation. Most of the affected brain regions suffered an initial volume deficit followed by growth at a normal rate, remaining smaller in irradiated brains compared with controls at all time points examined. The one exception was the olfactory bulb, which in addition to an early volume deficit, grew at a slower rate thereafter, resulting in a progressive volume deficit relative to controls. Immunohistochemical assessment revealed demyelination in white matter and loss of neural progenitor cells in the subgranular zone of the dentate gyrus and subventricular zone. Conclusions: MRI can detect regional differences in neuroanatomy and brain growth after whole-brain irradiation in the developing mouse. Developmental deficits in neuroanatomy persist, or even progress, and may serve as useful markers of late effects in mouse models. The high-throughput evaluation of brain development enabled by these methods may allow testing of strategies to mitigate late effects after pediatric cranial irradiation.

A ten-week biochemistry lab project studying wild-type and mutant bacterial alkaline phosphatase.

Science.gov (United States)

Witherow, D Scott

2016-11-12

This work describes a 10-week laboratory project studying wild-type and mutant bacterial alkaline phosphatase, in which students purify, quantitate, and perform kinetic assays on wild-type and selected mutants of the enzyme. Students also perform plasmid DNA purification, digestion, and gel analysis. In addition to simply learning important techniques, students acquire novel biochemical data in their kinetic analysis of mutant enzymes. The experiments are designed to build on students' work from week to week in a way that requires them to apply quantitative analysis and reasoning skills, reinforcing traditional textbook biochemical concepts. Students are assessed through lab reports focused on journal style writing, quantitative and conceptual question sheets, and traditional exams. © 2016 by The International Union of Biochemistry and Molecular Biology, 44(6):555-564, 2016. © 2016 The International Union of Biochemistry and Molecular Biology.

Morphometric characteristics of caudal cranial nerves at petroclival region in fetuses.

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Ozdogmus, Omer; Saban, Enis; Ozkan, Mazhar; Yildiz, Sercan Dogukan; Verimli, Ural; Cakmak, Ozgur; Arifoglu, Yasin; Sehirli, Umit

2016-06-01

Morphometric measurements of cranial nerves in posterior cranial fossa of fetus cadavers were carried out in an attempt to identify any asymmetry in their openings into the cranium. Twenty-two fetus cadavers (8 females, 14 males) with gestational age ranging between 22 and 38 weeks (mean 30 weeks) were included in this study. The calvaria were removed, the brains were lifted, and the cranial nerves were identified. The distance of each cranial nerve opening to midline and the distances between different cranial nerve openings were measured on the left and right side and compared. The mean clivus length and width were 21.2 ± 4.4 and 13.2 ± 1.5 mm, respectively. The distance of the twelfth cranial nerve opening from midline was shorter on the right side when compared with the left side (6.6 ± 1.1 versus 7.1 ± 0.8 mm, p = 0.038). Openings of other cranial nerves did not show such asymmetry with regard to their distance from midline, and the distances between different cranial nerves were similar on the left and right side. Cranial nerves at petroclival region seem to show minimal asymmetry in fetuses.

Plantarflexion Contracture in the mdx Mouse

Science.gov (United States)

Garlich, Michael W.; Baltgalvis, Kristen A.; Call, Jarrod A.; Dorsey, Lisa L.; Lowe, Dawn A.

2012-01-01

Objective Contractures are a major clinical issue for patients with muscular dystrophies. However, it is unknown whether contractures are present in the widely used mdx mouse model of Duchenne muscular dystrophy. Therefore, the objectives of this study were to develop methods to measure muscle contractures in mice, to determine whether plantarflexion contractures are present in mdx mice, and to analyze the composition of the major muscles involved. Design Hindlimbs of eight wild type and six mdx mice were assessed every 2 wks during the course of a 12-wk study. Assessments included range of motion and in vivo torques about the ankle. At the end of the study, mice were euthanized, and muscles were analyzed for composition. Results The mdx mice had ~10 degrees less dorsiflexion, increased passive torque moving the ankle into dorsiflexion, and an increased passive-to-active torque ratio relative to wild type mice. Gastrocnemius muscle composition alterations included increased wet mass, decreased protein content, and increased collagen. Conclusions The results indicate that mdx mice have plantarflexion contractures similar to those seen in children with Duchenne muscular dystrophy. In future studies, these measures can be used to assess strategies to slow the progression of contractures that occur with muscular dystrophies. PMID:21403594

A multiplex reverse transcription-nested polymerase chain reaction for detection and differentiation of wild-type and vaccine strains of canine distemper virus

Directory of Open Access Journals (Sweden)

Cui Shang-jin

2010-05-01

Full Text Available Abstract A multiplex reverse transcription-nested polymerase chain reaction (RT-nPCR method was developed for the detection and differentiation of wild-type and vaccine strains of canine distemper virus (CDV. A pair of primers (P1 and P4 specific for CDV corresponding to the highly conserved region of the CDV genome were used as a common primer pair in the first-round PCR of the nested PCR. Primers P2 specific for CDV wild-type strains, were used as the forward primer together with the common reverse primer P4 in the second round of nested PCR. Primers P3, P5 specific for CDV wild-type strain or vaccine strain, were used as the forward primer together with the common reverse primer P4+P6 in the second round of nested PCR. A fragment of 177 bp was amplified from vaccine strain genomic RNA, and a fragment of 247 bp from wild-type strain genomic RNA in the RT-nPCR, and two fragments of 247 bp and 177 bp were amplified from the mixed samples of vaccine and wild-type strains. No amplification was achieved for uninfected cells, or cells infected with Newcastle disease virus (NDV, canine parvovirus (CPV, canine coronavirus (CCV, rabies virus (RV, or canine adenovirus (CAV. The RT-nPCR method was used to detect 30 field samples suspected of canine distemper from Heilongjiang and Jilin Provinces, and 51 samples in Shandong province. As a result of 30 samples, were found to be wild-type-like, and 5 to be vaccine-strain-like. The RT-nPCR method can be used to effectively detect and differentiate wild-type CDV-infected dogs from dogs vaccinated with CDV vaccine, and thus can be used in clinical detection and epidemiological surveillance.

A multiplex reverse transcription-nested polymerase chain reaction for detection and differentiation of wild-type and vaccine strains of canine distemper virus

Science.gov (United States)

2010-01-01

A multiplex reverse transcription-nested polymerase chain reaction (RT-nPCR) method was developed for the detection and differentiation of wild-type and vaccine strains of canine distemper virus (CDV). A pair of primers (P1 and P4) specific for CDV corresponding to the highly conserved region of the CDV genome were used as a common primer pair in the first-round PCR of the nested PCR. Primers P2 specific for CDV wild-type strains, were used as the forward primer together with the common reverse primer P4 in the second round of nested PCR. Primers P3, P5 specific for CDV wild-type strain or vaccine strain, were used as the forward primer together with the common reverse primer P4+P6 in the second round of nested PCR. A fragment of 177 bp was amplified from vaccine strain genomic RNA, and a fragment of 247 bp from wild-type strain genomic RNA in the RT-nPCR, and two fragments of 247 bp and 177 bp were amplified from the mixed samples of vaccine and wild-type strains. No amplification was achieved for uninfected cells, or cells infected with Newcastle disease virus (NDV), canine parvovirus (CPV), canine coronavirus (CCV), rabies virus (RV), or canine adenovirus (CAV). The RT-nPCR method was used to detect 30 field samples suspected of canine distemper from Heilongjiang and Jilin Provinces, and 51 samples in Shandong province. As a result of 30 samples, were found to be wild-type-like, and 5 to be vaccine-strain-like. The RT-nPCR method can be used to effectively detect and differentiate wild-type CDV-infected dogs from dogs vaccinated with CDV vaccine, and thus can be used in clinical detection and epidemiological surveillance. PMID:20433759

Genomic resources for wild populations of the house mouse, Mus musculus and its close relative Mus spretus

Science.gov (United States)

Harr, Bettina; Karakoc, Emre; Neme, Rafik; Teschke, Meike; Pfeifle, Christine; Pezer, Željka; Babiker, Hiba; Linnenbrink, Miriam; Montero, Inka; Scavetta, Rick; Abai, Mohammad Reza; Molins, Marta Puente; Schlegel, Mathias; Ulrich, Rainer G.; Altmüller, Janine; Franitza, Marek; Büntge, Anna; Künzel, Sven; Tautz, Diethard

2016-01-01

Wild populations of the house mouse (Mus musculus) represent the raw genetic material for the classical inbred strains in biomedical research and are a major model system for evolutionary biology. We provide whole genome sequencing data of individuals representing natural populations of M. m. domesticus (24 individuals from 3 populations), M. m. helgolandicus (3 individuals), M. m. musculus (22 individuals from 3 populations) and M. spretus (8 individuals from one population). We use a single pipeline to map and call variants for these individuals and also include 10 additional individuals of M. m. castaneus for which genomic data are publically available. In addition, RNAseq data were obtained from 10 tissues of up to eight adult individuals from each of the three M. m. domesticus populations for which genomic data were collected. Data and analyses are presented via tracks viewable in the UCSC or IGV genome browsers. We also provide information on available outbred stocks and instructions on how to keep them in the laboratory. PMID:27622383

Ophthalmople gic cranial neuropathy: clinical case

OpenAIRE

N. S. Dozorova; A. S. Kotov; E. V. Mukhina

2018-01-01

Ophthalmoplegic cranial neuropathy (OCN) is a disease with unknown etiology, which manifests itself by episodes of intense headache, accompanied by completely or partially reversible dysfunction of the oculomotor nerve: ptosis, mydriasis and ophthalmoplegia. It is assumed that the pathology is demyelinating in nature, therefore in the International classification of headaches OCN excluded from rubric migraine and related to the painful cranial neuropathies. The question of the prevention and ...

Mid-aged and aged wild-type and progestin receptor knockout (PRKO) mice demonstrate rapid progesterone and 3alpha,5alpha-THP-facilitated lordosis.

Science.gov (United States)

Frye, C A; Sumida, K; Lydon, J P; O'Malley, B W; Pfaff, D W

2006-05-01

Progesterone (P) and its 5alpha-reduced metabolite, 3alpha-hydroxy-5alpha-pregnan-20-one (3alpha,5alpha-THP), facilitate sexual behavior of rodents via agonist-like actions at intracellular progestin receptors (PRs) and membrane GABA(A)/benzodiazepine receptor complexes (GBRs), respectively. Given that ovarian secretion of progestins declines with aging, whether or not senescent mice are responsive to progestins was of interest. Homozygous PR knockout (PRKO) or wild-type mice that were between 10-12 (mid-aged) or 20-24 (aged) months of age were administered P or 3alpha,5alpha-THP, and the effect on lordosis were examined. Effects of a progestin-priming regimen that enhances PR-mediated (experiment 1) or more rapid, PR-independent effects of progestins (experiments 2 and 3) on sexual behavior were examined. Levels of P, 3alpha,5alpha-THP, and muscimol binding were examined in tissues from aged mice (experiment 4). Wild-type, but not PRKO, mice were responsive when primed with 17beta-estradiol (E(2); 0.5 microg) and administered P (500 microg, subcutaneously). Mid-aged wild-type mice demonstrated greater increases in lordosis 6 h later compared to their pre-P, baseline test than did aged wild-type mice (experiment 1). Lordosis of younger and older wild-type, but not PRKO, mice was significantly increased within 5 min of intravenous (IV) administration of P (100 ng), compared with E(2)-priming alone (experiment 2). However, wild-type and PRKO mice demonstrated significant increases in lordosis 5 min after IV administration of 3alpha,5alpha-THP, an effect which was more pronounced in mid-aged than in aged animals (100 ng-experiment 3). In tissues from aged wild-type and PRKO mice, levels of P, 3alpha,5alpha-THP, and muscimol binding were increased by P administration (experiment 4). PR binding was lower in the cortex of PRKO than that of wild-type mice. Mid-aged and aged PRKO and wild-type mice demonstrated rapid P or 3alpha,5alpha-THP-facilitated lordosis that may be

MicroRNA-Attenuated Clone of Virulent Semliki Forest Virus Overcomes Antiviral Type I Interferon in Resistant Mouse CT-2A Glioma.

Science.gov (United States)

Martikainen, Miika; Niittykoski, Minna; von und zu Fraunberg, Mikael; Immonen, Arto; Koponen, Susanna; van Geenen, Maartje; Vähä-Koskela, Markus; Ylösmäki, Erkko; Jääskeläinen, Juha E; Saksela, Kalle; Hinkkanen, Ari

2015-10-01

Glioblastoma is a terminal disease with no effective treatment currently available. Among the new therapy candidates are oncolytic viruses capable of selectively replicating in cancer cells, causing tumor lysis and inducing adaptive immune responses against the tumor. However, tumor antiviral responses, primarily mediated by type I interferon (IFN-I), remain a key problem that severely restricts viral replication and oncolysis. We show here that the Semliki Forest virus (SFV) strain SFV4, which causes lethal encephalitis in mice, is able to infect and replicate independent of the IFN-I defense in mouse glioblastoma cells and cell lines originating from primary human glioblastoma patient samples. The ability to tolerate IFN-I was retained in SFV4-miRT124 cells, a derivative cell line of strain SFV4 with a restricted capacity to replicate in neurons due to insertion of target sites for neuronal microRNA 124. The IFN-I tolerance was associated with the viral nsp3-nsp4 gene region and distinct from the genetic loci responsible for SFV neurovirulence. In contrast to the naturally attenuated strain SFV A7(74) and its derivatives, SFV4-miRT124 displayed increased oncolytic potency in CT-2A murine astrocytoma cells and in the human glioblastoma cell lines pretreated with IFN-I. Following a single intraperitoneal injection of SFV4-miRT124 into C57BL/6 mice bearing CT-2A orthotopic gliomas, the virus homed to the brain and was amplified in the tumor, resulting in significant tumor growth inhibition and improved survival. Although progress has been made in development of replicative oncolytic viruses, information regarding their overall therapeutic potency in a clinical setting is still lacking. This could be at least partially dependent on the IFN-I sensitivity of the viruses used. Here, we show that the conditionally replicating SFV4-miRT124 virus shares the IFN-I tolerance of the pathogenic wild-type SFV, thereby allowing efficient targeting of a glioma that is refractory

A Longitudinal Motor Characterisation of the HdhQ111 Mouse Model of Huntington's Disease.

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Yhnell, Emma; Dunnett, Stephen B; Brooks, Simon P

2016-05-31

Huntington's disease (HD) is a rare, incurable neurodegenerative disorder caused by a CAG trinucleotide expansion with the first exon of the huntingtin gene. Numerous knock-in mouse models are currently available for modelling HD. However, before their use in scientific research, these models must be characterised to determine their face and predictive validity as models of the disease and their reliability in recapitulating HD symptoms. Manifest HD is currently diagnosed upon the onset of motor symptoms, thus we sought to longitudinally characterise the progression and severity of motor signs in the HdhQ111 knock-in mouse model of HD, in heterozygous mice. An extensive battery of motor tests including: rotarod, inverted lid test, balance beam, spontaneous locomotor activity and gait analysis were applied longitudinally to a cohort of HdhQ111 heterozygous mice in order to progressively assess motor function. A progressive failure to gain body weight was demonstrated from 11 months of age and motor problems in all measures of balance beam performance were shown in HdhQ111 heterozygous animals in comparison to wild type control animals from 9 months of age. A decreased latency to fall from the rotarod was demonstrated in HdhQ111 heterozygous animals in comparison to wild type animals, although this was not progressive with time. No genotype specific differences were demonstrated in any of the other motor tests included in the test battery. The HdhQ111 heterozygous mouse demonstrates a subtle and progressive motor phenotype that begins at 9 months of age. This mouse model represents an early disease stage and would be ideal for testing therapeutic strategies that require elongated lead-in times, such as viral gene therapies or striatal transplantation.

Multiple cranial nerve palsies complicating tympanomastoiditis: case ...

African Journals Online (AJOL)

Otitis media either acute or chronic, is not uncommon in childhood. Multiple cranial nerve palsies occuring as a complication of either form of otitis media is unusual. A case of a nine year old boy with chronic suppurative otitis media with associated mastoiditis complicated with ipsilateral multiple cranial nerve palsies is ...

Lactobacillus apodemi sp. nov., a tannase-producing species isolated from wild mouse faeces.

Science.gov (United States)

Osawa, Ro; Fujisawa, Tomohiko; Pukall, Rüdiger

2006-07-01

A Gram-positive, rod-shaped, non-endospore-forming bacterium, strain ASB1(T), able to degrade tannin, was isolated from faeces of the Japanese large wood mouse, Apodemus speciosus. Comparative analysis of the 16S rRNA gene sequence revealed that the strain could be assigned as a member of the genus Lactobacillus. The nearest phylogenetic neighbours were determined as Lactobacillus animalis DSM 20602(T) (98.9 % 16S rRNA gene sequence similarity) and Lactobacillus murinus ASF 361 (98.9 %). Subsequent polyphasic analysis, including automated ribotyping and DNA-DNA hybridization experiments, confirmed that the isolate represents a novel species, for which the name Lactobacillus apodemi sp. nov. is proposed. The DNA G+C content of the novel strain is 38.5 mol%. The cell-wall peptidoglycan is of type A4alpha L-lys-D-asp. The type strain is ASB1(T) (=DSM 16634(T)=CIP 108913(T)).

Cranial osteopathy: its fate seems clear

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Hartman Steve E

2006-06-01

Full Text Available Abstract Background According to the original model of cranial osteopathy, intrinsic rhythmic movements of the human brain cause rhythmic fluctuations of cerebrospinal fluid and specific relational changes among dural membranes, cranial bones, and the sacrum. Practitioners believe they can palpably modify parameters of this mechanism to a patient's health advantage. Discussion This treatment regime lacks a biologically plausible mechanism, shows no diagnostic reliability, and offers little hope that any direct clinical effect will ever be shown. In spite of almost uniformly negative research findings, "cranial" methods remain popular with many practitioners and patients. Summary Until outcome studies show that these techniques produce a direct and positive clinical effect, they should be dropped from all academic curricula; insurance companies should stop paying for them; and patients should invest their time, money, and health elsewhere.

Literature review of cranial nerve injuries during carotid endarterectomy.

Science.gov (United States)

Sajid, M S; Vijaynagar, B; Singh, P; Hamilton, G

2007-01-01

In the recent prospective randomised trials on carotid endarterectomy (CEA), the incidence of cranial nerve injuries (CNI) are reported to be higher than in previously published studies. The objective of this study is to review the incidence of post CEA cranial nerve injury and to discover whether it has changed in the last 25 years after many innovations in vascular surgery. Generic terms including carotid endarterectomy, cranial nerve injuries, post CEA complications and cranial nerve deficit after neck surgery were used to search a variety of electronic databases. Based on selection criteria, decisions regarding inclusion and exclusion of primary studies were made. The incidence of CNI before and after 1995 was compared. We found 31 eligible studies from the literature. Patients who underwent CEA through any approach were included in the study. All patients had cranial nerves examined both before and after surgery. The total number of patients who had CEA before 1995 was 3521 with 10.6% CNI (352 patients) and after 1995, 7324 patients underwent CEA with 8.3% CNI (614 patients). Cranial nerves XII, X and VII were most commonly involved (rarely IX and XI). Statistical analysis showed that the incidence of CNI has decreased (X(2) = 5.89 + 0.74 = 6.63 => p-value = 0.0100). CNI is still a significant postoperative complication of carotid endarterectomy. Despite increasing use of CEA, the incidence of CNI has decreased probably because of increased awareness of the possibility of cranial nerve damage.

Epithelial V-like antigen mediates efficacy of anti-alpha₄ integrin treatment in a mouse model of multiple sclerosis.

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Erik Wright

Full Text Available Natalizumab inhibits the transmigration of activated T lymphocytes into the brain and is highly efficacious in multiple sclerosis (MS. However, from a pharmacogenomic perspective, its efficacy and safety in specific patients remain unclear. Here our goal was to analyze the effects of epithelial V-like antigen (EVA on anti-alpha₄ integrin (VLA4 efficacy in a mouse model of MS, experimental autoimmune encephalomyelitis (EAE. EVA has been previously characterized in human CD4 T lymphocytes, mouse thymic development, and choroid plexus epithelial cells. Further analysis here demonstrated expression in B lymphocytes and an increase in EVA⁺ lymphocytes following immunization. Following active induction of EAE using the MOG³⁵⁻⁵⁵ active immunization model, EVA deficient mice developed more severe EAE and white matter tissue injury as compared to wild type controls. This severe EAE phenotype did not respond to anti-VLA4 treatment. In both the control antibody and anti-VLA4 conditions, these mice demonstrated persistent CNS invasion of mature B lymphocyte (CD19⁺, CD21⁺, sIgG⁺, increased serum autoantibody levels, and extensive complement and IgG deposition within lesions containing CD5⁺IgG⁺ cells. Wild type mice treated with control antibody also demonstrated the presence of CD19⁺, CD21⁺, sIgG⁺ cells within the CNS during peak EAE disease severity and detectable serum autoantibody. In contrast, wild type mice treated with anti-VLA4 demonstrated reduced serum autoantibody levels as compared to wild type controls and EVA-knockout mice. As expected, anti-VLA4 treatment in wild type mice reduced the total numbers of all CNS mononuclear cells and markedly decreased CD4 T lymphocyte invasion. Treatment also reduced the frequency of CD19⁺, CD21⁺, sIgG⁺ cells in the CNS. These results suggest that anti-VLA4 treatment may reduce B lymphocyte associated autoimmunity in some individuals and that EVA expression is necessary for an

Critical off-target effects of the widely used Rac1 inhibitors NSC23766 and EHT1864 in mouse platelets

DEFF Research Database (Denmark)

Dütting, Sebastian; Heidenreich, Julius; Cherpokova, Deya

2015-01-01

BACKGROUND: Platelet aggregation at sites of vascular injury is essential for normal hemostasis, but may also cause pathological vessel occlusion. Rho GTPases are molecular switches that regulate essential cellular processes and they have pivotal functions in the cardiovascular system. Rac1......, have been characterized in different cell types, demonstrating high specificity for Rac1 or Rac, respectively. OBJECTIVES: We sought to analyze the specificity of NSC23766 and EHT1864. METHODS: Platelet function was assessed in mouse wild-type and Rac1-deficient platelets by using flow cytometric...... function tests. Both inhibitors induced a Rac1-specific inhibition of platelet spreading, but also markedly impaired agonist-induced activation of Rac1(-/-) platelets. Furthermore, GPIb-mediated signaling was dramatically inhibited by NSC23766 in both wild-type and Rac1-deficient platelets. Importantly...

The role of the mesenchyme in mouse neural fold elevation. II. Patterns of hyaluronate synthesis and distribution in embryos developing in vitro

International Nuclear Information System (INIS)

Morris-Wiman, J.; Brinkley, L.L.

1990-01-01

Hyaluronate (HA) distribution patterns were examined in the cranial mesenchyme underlying the mesencephalic neural folds of mouse embryos maintained in roller tube culture. Using standard image-processing techniques, the digitized images of Alcian blue-stained or 3H-glucosamine-labeled sections digested with an enzyme specific for HA, were subtracted from adjacent, undigested sections. The resultant difference picture images (DPI) accurately depicted the distribution of stained or labeled HA within the cranial mesenchyme. 3H-glucosamine-labeled HA was distributed uniformly throughout the cranial mesenchyme as 12, 18, and 24 hr of culture. By contrast, the mesenchyme was uniformly stained with Alcian blue at 12 hr, but stain intensity decreased in the central regions of the mesenchyme at 18 and 24 hr. HA distribution patterns were also examined in the cranial mesenchyme of embryos cultured in the presence of diazo-oxo-norleucine (DON), a glutamine analogue that inhibits glycosaminoglycan and glycoprotein synthesis. In DON-treated mesenchyme, Alcian blue staining of HA was decreased from that in controls at 12, 18, and 24 hr. However, incorporation of 3H-glucosamine into HA was increased. The distribution of labeled HA within treated mesenchyme as 12, 18, and 24 hr resembled that in controls at 12 hr. These results indicate that the distribution of HA within the cranial mesenchyme of normal mouse embryos during neural fold elevation and convergence is not determined solely by regional differences in HA synthesis. We propose that HA distribution patterns result from the expansion of the HA-rich extracellular matrix of the central mesenchyme regions. This expansion may play a major role in fold elevation. These results also suggest that DON treatment reversibly inhibits HA synthesis

Arterial supply of the upper cranial nerves: a comprehensive review.

Science.gov (United States)

Hendrix, Philipp; Griessenauer, Christoph J; Foreman, Paul; Shoja, Mohammadali M; Loukas, Marios; Tubbs, R Shane

2014-11-01

The arterial supply to the upper cranial nerves is derived from a complex network of branches derived from the anterior and posterior cerebral circulations. We performed a comprehensive literature review of the arterial supply of the upper cranial nerves with an emphasis on clinical considerations. Arteries coursing in close proximity to the cranial nerves regularly give rise to small vessels that supply the nerve. Knowledge of the arteries supplying the cranial nerves is of particular importance during surgical approaches to the skull base. © 2014 Wiley Periodicals, Inc.

Effects of major histocompatibility complex class II knockout on mouse bone mechanical properties during development

Science.gov (United States)

Simske, Steven J.; Bateman, Ted A.; Smith, Erin E.; Ferguson, Virginia L.; Chapes, Stephen K.

2002-01-01

We investigated the effect of major histocompatibility complex class II (MHC II) knockout on the development of the mouse peripheral skeleton. These C2D mice had less skeletal development at 8, 12 and 16 weeks of age compared to wild-type C57BL/6J (B6) male mice. The C2D mice had decreased femur mechanical, geometric and compositional measurements compared to wild type mice at each of these ages. C2D femur stiffness (S), peak force in 3-pt bending (Pm), and mineral mass (Min-M) were 74%, 64% and 66%, respectively, of corresponding B6 values at 8 weeks of age. Similar differences were measured at 12 weeks (for which C2D femoral S, Pm and Min-M were 71%, 72% and 73%, respectively, of corresponding B6 values) and at 16 weeks (for which C2D femoral S, Pm and Min-M were 80%, 66% and 61%, respectively, of corresponding B6 values). MHC II knockout delays the development of adult bone properties and is accompanied by lower body mass compared to wild-type controls.

Introduction of the human proα1(I) collagen gene into proα1(I)-deficient Mov-13 mouse cells leads to formation of functional mouse-human hybrid type I collagen

International Nuclear Information System (INIS)

Schnieke, A.; Dziadek, M.; Bateman, J.; Mascara, T.; Harbers, K.; Gelinas, R.; Jaenisch, R.

1987-01-01

The Mov-13 mouse strain carries a retroviral insertion in the proα1(I) collagen gene that prevents transcription of the gene. Cell lines derived from homozygous embryos do not express type I collagen although normal amounts of proα2 mRNA are synthesized. The authors have introduced genomic clones of either the human or mouse proα1(I) collagen gene into homozygous cell lines to assess whether the human or mouse proα1(I) chains can associate with the endogenous mouse proα2(I) chain to form stable type I collagen. The human gene under control of the simian virus 40 promoter was efficiently transcribed in the transfected cells. Protein analyses revealed that stable heterotrimers consisting of two human α1 chains and one mouse α2 chain were formed and that type I collagen was secreted by the transfected cells at normal rates. However, the electrophoretic migration of both α1(I) and α2(I) chains in the human-mouse hybrid molecules were retarded, compared to the α(I) chains in control mouse cells. Inhibition of the posttranslational hydroxylation of lysine and proline resulted in comigration of human and mouse α1 and α2 chains, suggesting that increased posttranslational modification caused the altered electrophoretic migration in the human-mouse hybrid molecules. Amino acid sequence differences between the mouse and human α chains may interfere with the normal rate of helix formation and increase the degree of posttranslational modifications similar to those observed in patients with lethal perinatal osteogenesis imperfecta. The Mov-13 mouse system should allow the authors to study the effect specific mutations introduced in transfected proα1(I) genes have on the synthesis, assembly, and function of collagen I

Cranial and dental abnormalities of the endangered red wolf Canis rufus

Science.gov (United States)

Federoff, Nicholas E.; Nowak, Ronald M.

1998-01-01

Three skulls of captive-raised female endangered red wolves (Canis rufus) exhibited severe malocclusion of the jaws. Cranial and dental abnormalities (including crowding of upper toothrows, and an extra tooth behind the lower left M3 in one of the three mandibles) were also evident. Ratios of alveolar length of maxillary toothrow to maximum width across the outer sides of crowns of P4 were significantly different (p=0.008) compared to unaffected skulls. Significant differences were also evident when ratios of maximum width across inner edges of alveoli of P1 to alveolar length of maxillary toothrow and maximum width across outer sides of crowns of P4 were compared between the two groups. Although the three skulls all exhibited malocclusion, the abnormality expressed itself differently in relation to the effects to each skull. Captive inbreeding may increase the probability and frequency of expressing these anomalies, although inbreeding coefficients calculated for the wolves expressing malocclusion were not considered high (0.0313-0.0508). A wild female red wolf specimen captured in 1921 in Arkansas also exhibited the malocclusion, although not as severely as in the captive females. This demonstrates that this trait was present in wild populations prior to, and not a result of, the captive breeding program.

Changes in fatty acid content and composition between wild type and CsHMA3 overexpressing Camelina sativa under heavy-metal stress.

Science.gov (United States)

Park, Won; Feng, Yufeng; Kim, Hyojin; Suh, Mi Chung; Ahn, Sung-Ju

2015-09-01

Under heavy-metal stress, CsHMA3 overexpressing transgenic Camelina plants displayed not only a better quality, but also a higher quantity of unsaturated fatty acids in their seeds compared with wild type. Camelina sativa L. belongs to the Brassicaceae family and is frequently used as a natural vegetable oil source, as its seeds contain a high content of fatty acids. In this study, we observed that, when subjected to heavy metals (Cd, Co, Zn and Pb), the seeds of CsHMA3 (Heavy-Metal P1B-ATPase 3) transgenic lines retained their original golden yellow color and smooth outline, unlike wild-type seeds. Furthermore, we investigated the fatty acids content and composition of wild type and CsHMA3 transgenic lines after heavy metal treatments compared to the control. The results showed higher total fatty acid amounts in seeds of CsHMA3 transgenic lines compared with those in wild-type seeds under heavy-metal stresses. In addition, the compositions of unsaturated fatty acids-especially 18:1 (oleic acid), 18:2 (linoleic acid; only in case of Co treatment), 18:3 (linolenic acid) and 20:1 (eicosenoic acid)-in CsHMA3 overexpressing transgenic lines treated with heavy metals were higher than those of wild-type seeds under the same conditions. Furthermore, reactive oxygen species (ROS) contents in wild-type leaves and roots when treated with heavy metal were higher than in CsHMA3 overexpressing transgenic lines. These results indicate that overexpression of CsHMA3 affects fatty acid composition and content-factors that are responsible for the fuel properties of biodiesel-and can alleviate ROS accumulation caused by heavy-metal stresses in Camelina. Due to these factors, we propose that CsHMA3 transgenic Camelina can be used for phytoremediation of metal-contaminated soil as well as for oil production.

The Use of EGFR Tyrosine Kinase Inhibitors in EGFR Wild-Type Non-Small-Cell Lung Cancer.

Science.gov (United States)

Stinchcombe, Thomas E

2016-04-01

The objective response rate and progression-free survival observed with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) in patients with metastatic epidermal growth factor receptor (EGFR) wild-type non-small cell lung cancer (NSCLC) are modest. The adverse events associated with EGFR TKIs are manageable but they must be considered in the context of the limited efficacy. The development of anti-PD-1 immunotherapy as second-line therapy has reduced the role of EGFR TKIs in EGFR wild-type NSCLC. Recently, there has been increased recognition of the benefit of the earlier integration of palliative care and symptom management, and this is reasonable alternative to treatment with an EGFR TKI for many patients. My practice pattern for patients with EGFR wild-type NSCLC is platinum-based chemotherapy as first-line therapy, immunotherapy as second-line therapy, and single-agent chemotherapy as third-line therapy for patients with preserved performance status who want to pursue further therapy. Only a small proportion of patients are eligible for fourth-line therapy, and I prefer to enroll them in clinical trials rather than use EGFR TKIs. I suspect that the use of EGFR TKIs in clinical use and as a comparator arm for clinical trials will continue to decline over the next several years.

Round Spermatid Injection Rescues Female Lethality of a Paternally Inherited Xist Deletion in Mouse.

Directory of Open Access Journals (Sweden)

Federica Federici

2016-10-01

Full Text Available In mouse female preimplantation embryos, the paternal X chromosome (Xp is silenced by imprinted X chromosome inactivation (iXCI. This requires production of the noncoding Xist RNA in cis, from the Xp. The Xist locus on the maternally inherited X chromosome (Xm is refractory to activation due to the presence of an imprint. Paternal inheritance of an Xist deletion (XpΔXist is embryonic lethal to female embryos, due to iXCI abolishment. Here, we circumvented the histone-to-protamine and protamine-to-histone transitions of the paternal genome, by fertilization of oocytes via injection of round spermatids (ROSI. This did not affect initiation of XCI in wild type female embryos. Surprisingly, ROSI using ΔXist round spermatids allowed survival of female embryos. This was accompanied by activation of the intact maternal Xist gene, initiated with delayed kinetics, around the morula stage, resulting in Xm silencing. Maternal Xist gene activation was not observed in ROSI-derived males. In addition, no Xist expression was detected in male and female morulas that developed from oocytes fertilized with mature ΔXist sperm. Finally, the expression of the X-encoded XCI-activator RNF12 was enhanced in both male (wild type and female (wild type as well as XpΔXist ROSI derived embryos, compared to in vivo fertilized embryos. Thus, high RNF12 levels may contribute to the specific activation of maternal Xist in XpΔXist female ROSI embryos, but upregulation of additional Xp derived factors and/or the specific epigenetic constitution of the round spermatid-derived Xp are expected to be more critical. These results illustrate the profound impact of a dysregulated paternal epigenome on embryo development, and we propose that mouse ROSI can be used as a model to study the effects of intergenerational inheritance of epigenetic marks.

Autophagy and UPR in alpha-crystallin mutant knock-in mouse models of hereditary cataracts.

Science.gov (United States)

Andley, Usha P; Goldman, Joshua W

2016-01-01

Knock-in mice provide useful models of congenital and age-related cataracts caused by α-crystallin mutations. R49C αA-crystallin and R120G αB-crystallin mutations are linked with hereditary cataracts. Knock-in αA-R49C+/- heterozygotes develop cataracts by 1-2months, whereas homozygote mice have cataracts at birth. The R49C mutation drastically reduces lens protein water solubility and causes cell death in knock-in mouse lenses. Mutant crystallin cannot function as a chaperone, which leads to protein aggregation and lens opacity. Protein aggregation disrupts the lens fiber cell structure and normal development and causes cell death in epithelial and fiber cells. We determined what aspects of the wild-type phenotype are age-dependently altered in the mutant lens. Wild-type, heterozygote (αA-R49C+/-), and homozygote (αA-R49C+/+) mouse lenses were assessed pre- and postnatally for lens morphology (electron microscopy, immunohistochemistry), and autophagy or unfolded protein response markers (immunoblotting). Morphology was altered by embryonic day 17 in R49C+/+ lenses; R49C+/- lens morphology was unaffected at this stage. Active autophagy in the lens epithelium of mutant lenses was indicated by the presence of autophagosomes using electron microscopy. Protein p62 levels, which are degraded specifically by autophagy, increased in αA-R49C mutant versus wild-type lenses, suggesting autophagy inhibition in the mutant lenses. The unfolded protein response marker XBP-1 was upregulated in adult lenses of αB-R120G+/+ mice, suggesting its role in lens opacification. Mutated crystallins alter lens morphology, autophagy, and stress responses. Therapeutic modulation of autophagic pathways may improve protein degradation in cataractous lenses and reduce lens opacity. This article is part of a Special Issue entitled Crystallin Biochemistry in Health and Disease. Copyright © 2015 Elsevier B.V. All rights reserved.

Accounting for cranial vault growth in experimental design.

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Power, Stephanie M; Matic, Damir B; Holdsworth, David W

2014-05-01

Earlier studies have not accounted for continued growth when using the rat calvarial defect model to evaluate bone healing in vivo. The purpose of this study was: 1) to calculate rat cranial vault growth over time; and 2) to determine the effects of accounting for growth on defect healing. Bilateral parietal defects were created in 10 adult Wistar rats. Serial microscopic computerized tomography scans were performed. Bone mineral content (BMC) measured according to standard technique and repeated accounting for cranial growth over time was compared with the use of parametric and nonparametric tests. Cranial vault growth continued through 22 weeks of age, increasing 7.5% in width and 9.1% in length, and calvarial defects expanded proportionately. BMC was greater within defects accounting for growth 2-12 weeks postoperatively (P accounting for cranial growth given advances in serial imaging techniques. Crown Copyright © 2014. Published by Mosby, Inc. All rights reserved.

Establishment of new transmissible and drug-sensitive human immunodeficiency virus type 1 wild types due to transmission of nucleoside analogue-resistant virus.

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de Ronde, A; van Dooren, M; van Der Hoek, L; Bouwhuis, D; de Rooij, E; van Gemen, B; de Boer, R; Goudsmit, J

2001-01-01

Sequence analysis of human immunodeficiency virus type 1 (HIV-1) from 74 persons with acute infections identified eight strains with mutations in the reverse transcriptase (RT) gene at positions 41, 67, 68, 70, 215, and 219 associated with resistance to the nucleoside analogue zidovudine (AZT). Follow-up of the fate of these resistant HIV-1 strains in four newly infected individuals revealed that they were readily replaced by sensitive strains. The RT of the resistant viruses changed at amino acid 215 from tyrosine (Y) to aspartic acid (D) or serine (S), with asparagine (N) as a transient intermediate, indicating the establishment of new wild types. When we introduced these mutations and the original threonine (T)-containing wild type into infectious molecular clones and assessed their competitive advantage in vitro, the order of fitness was in accord with the in vivo observations: 215Y types with D, S, or N residues at position 215 may be warranted in order to estimate the threat to long-term efficacy of regimens including nucleoside analogues.

Multiple cranial neuropathies without limb involvements: guillain-barre syndrome variant?

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Yu, Ju Young; Jung, Han Young; Kim, Chang Hwan; Kim, Hyo Sang; Kim, Myeong Ok

2013-10-01

Acute multiple cranial neuropathies are considered as variant of Guillain-Barre syndrome, which are immune-mediated diseases triggered by various cases. It is a rare disease which is related to infectious, inflammatory or systemic diseases. According to previous case reports, those affected can exhibit almost bilateral facial nerve palsy, then followed by bulbar dysfunctions (cranial nerves IX and X) accompanied by limb weakness and walking difficulties due to motor and/or sensory dysfunctions. Furthermore, reported cases of the acute multiple cranial neuropathies show electrophysiological abnormalities compatible with the typical Guillain-Barre syndromes (GBS). We recently experienced a patient with a benign infectious disease who subsequently developed symptoms of variant GBS. Here, we describe the case of a 48-year-old male patient who developed multiple symptoms of cranial neuropathy without limb weakness. His laboratory findings showed a positive result for anti-GQ1b IgG antibody. As compared with previously described variants of GBS, the patient exhibited widespread cranial neuropathy, which included neuropathies of cranial nerves III-XII, without limb involvement or ataxia.

Effects of age and liquid holding on the UV-radiation sensitivities of wild-type and mutant Caenorhabditis elegans dauer larvae

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Hartman, P S

1984-01-01

The dauer larva is a facultative developmental stage in the life cycle of the nematode Caenorhabditis elegans. Dauer larvae, which can survive under starvation for over 60 days, resume normal development when feeding is resumed. Wild-type (N2) and 4 radiation-sensitive (rad) mutant dauer larvae were tested for their abilities to develop into adults after UV-irradiation. The rad-3 mutant was over 30 times as sensitive as N2; rad-1, rad-2 and rad-7 mutants were not hypersensitive. Irradiation also delayed development in survivors. Wild-type dauer larvae did not differ in radiation sensitivity from 0 through 50 days of age. There was no liquid holding recovery (LHR); that is, survival did not increase when wild-type dauer larvae were held in buffer after irradiation. (orig.). 28 refs.; 4 figs.

Genotyping assay for differentiation of wild-type and vaccine viruses in subjects immunized with live attenuated influenza vaccine.

Directory of Open Access Journals (Sweden)

Victoria Matyushenko

Full Text Available Live attenuated influenza vaccines (LAIVs are considered as safe and effective tool to control influenza in different age groups, especially in young children. An important part of the LAIV safety evaluation is the detection of vaccine virus replication in the nasopharynx of the vaccinees, with special attention to a potential virus transmission to the unvaccinated close contacts. Conducting LAIV clinical trials in some geographical regions with year-round circulation of influenza viruses warrants the development of robust and reliable tools for differentiating vaccine viruses from wild-type influenza viruses in nasal pharyngeal wash (NPW specimens of vaccinated subjects. Here we report the development of genotyping assay for the detection of wild-type and vaccine-type influenza virus genes in NPW specimens of young children immunized with Russian-backbone seasonal trivalent LAIV using Sanger sequencing from newly designed universal primers. The new primer set allowed amplification and sequencing of short fragments of viral genes in NPW specimens and appeared to be more sensitive than conventional real-time RT-PCR protocols routinely used for the detection and typing/subtyping of influenza virus in humans. Furthermore, the new assay is capable of defining the origin of wild-type influenza virus through BLAST search with the generated sequences of viral genes fragments.

Comparison of collagen fibre architecture between slow-twitch cranial and fast-twitch caudal parts of broiler M. latissimus dorsi.

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Nakamura, Y N; Iwamoto, H; Tabata, S; Ono, Y

2003-07-01

1. Collagen fibre architectures of perimysium and endomysium in the slow-twitch cranial and fast-twitch caudal parts of broiler M. latissimus dorsi were compared. 2. Type I and III collagens were distributed in both perimysium and endomysium as indicated by their positive immunohistochemical reactions to polyclonal antibodies. 3. Cells invested by endomysium with no myofibres were larger in the cranial part because of the presence of larger slow-twitch myofibres. The honeycomb structure of endomysium was divided into several parts by thick perimysium. 4. The thick perimysial collagen fibres with parallel fibrils, which were interconnected by the loose reticular fibrils and thin fibres, were more numerous and thicker in the cranial part than the caudal. 5. Thick endomysial sidewall of cells in the cranial part was composed of a rougher reticulum of slightly thicker collagen fibrils compared with the thin sidewall in the caudal part. 6. These results indicated that both perimysial constitutions of collagen fibres and endomysial collagen fibrils had attained much larger growth in the slow-twitch cranial part than the fast-twitch caudal in broiler latissimus dorsi muscle.

Cranial computerized tomography in children suffering from acute leukemia

International Nuclear Information System (INIS)

Metz, O.

1981-01-01

Cranial computerized (axial) tomography permits a more complete neurologic supervision of children with acute leukemia and a better knowledge of the frequency and varieties of cerebral complications in leukemia. Endocranial complications in acute leukemia are essentially infiltrative, hemorrhagic, infectious or iatrogenic. Cranial computerized tomography can demonstrate cerebral changes in meningeal leukemia, hemorrhages, calcifications, brain atrophy or leukencephalopathy. The preliminary results of cranial computerized tomography in childhood leukemia suggest that the iatrogenic main lesion of the brain due to combined radiation-chemotherapy is atrophy whereas that of the intrathecal cytostatic therapy is demyelination. Accurate diagnostics and control of possible cerebral complications in therapy of leukemia is essentially for appropriate therapeutic management. For that cranial computerized tomography is the best method to a effective supervision of the brain. (author)

Fully-Automated μMRI Morphometric Phenotyping of the Tc1 Mouse Model of Down Syndrome.

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Nick M Powell

Full Text Available We describe a fully automated pipeline for the morphometric phenotyping of mouse brains from μMRI data, and show its application to the Tc1 mouse model of Down syndrome, to identify new morphological phenotypes in the brain of this first transchromosomic animal carrying human chromosome 21. We incorporate an accessible approach for simultaneously scanning multiple ex vivo brains, requiring only a 3D-printed brain holder, and novel image processing steps for their separation and orientation. We employ clinically established multi-atlas techniques-superior to single-atlas methods-together with publicly-available atlas databases for automatic skull-stripping and tissue segmentation, providing high-quality, subject-specific tissue maps. We follow these steps with group-wise registration, structural parcellation and both Voxel- and Tensor-Based Morphometry-advantageous for their ability to highlight morphological differences without the laborious delineation of regions of interest. We show the application of freely available open-source software developed for clinical MRI analysis to mouse brain data: NiftySeg for segmentation and NiftyReg for registration, and discuss atlases and parameters suitable for the preclinical paradigm. We used this pipeline to compare 29 Tc1 brains with 26 wild-type littermate controls, imaged ex vivo at 9.4T. We show an unexpected increase in Tc1 total intracranial volume and, controlling for this, local volume and grey matter density reductions in the Tc1 brain compared to the wild-types, most prominently in the cerebellum, in agreement with human DS and previous histological findings.

The use of urinary proteomics in the assessment of suitability of mouse models for ageing.

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Nkuipou-Kenfack, Esther; Schanstra, Joost P; Bajwa, Seerat; Pejchinovski, Martin; Vinel, Claire; Dray, Cédric; Valet, Philippe; Bascands, Jean-Loup; Vlahou, Antonia; Koeck, Thomas; Borries, Melanie; Busch, Hauke; Bechtel-Walz, Wibke; Huber, Tobias B; Rudolph, Karl L; Pich, Andreas; Mischak, Harald; Zürbig, Petra

2017-01-01

Ageing is a complex process characterised by a systemic and progressive deterioration of biological functions. As ageing is associated with an increased prevalence of age-related chronic disorders, understanding its underlying molecular mechanisms can pave the way for therapeutic interventions and managing complications. Animal models such as mice are commonly used in ageing research as they have a shorter lifespan in comparison to humans and are also genetically close to humans. To assess the translatability of mouse ageing to human ageing, the urinary proteome in 89 wild-type (C57BL/6) mice aged between 8-96 weeks was investigated using capillary electrophoresis coupled to mass spectrometry (CE-MS). Using age as a continuous variable, 295 peptides significantly correlated with age in mice were identified. To investigate the relevance of using mouse models in human ageing studies, a comparison was performed with a previous correlation analysis using 1227 healthy subjects. In mice and humans, a decrease in urinary excretion of fibrillar collagens and an increase of uromodulin fragments was observed with advanced age. Of the 295 peptides correlating with age, 49 had a strong homology to the respective human age-related peptides. These ortholog peptides including several collagen (N = 44) and uromodulin (N = 5) fragments were used to generate an ageing classifier that was able to discriminate the age among both wild-type mice and healthy subjects. Additionally, the ageing classifier depicted that telomerase knock-out mice were older than their chronological age. Hence, with a focus on ortholog urinary peptides mouse ageing can be translated to human ageing.

Plasticity-Related Gene 1 Affects Mouse Barrel Cortex Function via Strengthening of Glutamatergic Thalamocortical Transmission

OpenAIRE

Unichenko, Petr; Kirischuk, Sergei; Yang, Jenq-Wei; Baumgart, Jan; Roskoden, Thomas; Schneider, Patrick; Sommer, Angela; Horta, Guilherme; Radyushkin, Konstantin; Nitsch, Robert; Vogt, Johannes; Luhmann, Heiko J.

2016-01-01

Plasticity-related gene-1 (PRG-1) is a brain-specific protein that modulates glutamatergic synaptic transmission. Here we investigated the functional role of PRG-1 in adolescent and adult mouse barrel cortex both in vitro and in vivo. Compared with wild-type (WT) animals, PRG-1-deficient (KO) mice showed specific behavioral deficits in tests assessing sensorimotor integration and whisker-based sensory discrimination as shown in the beam balance/walking test and sandpaper tactile discriminatio...

Unique Safety Issues Associated with Virus Vectored Vaccines: Potential for and Theoretical Consequences of Recombination with Wild Type Virus Strains

Science.gov (United States)

Condit, Richard C.; Williamson, Anna-Lise; Sheets, Rebecca; Seligman, Stephen J.; Monath, Thomas P.; Excler, Jean-Louis; Gurwith, Marc; Bok, Karin; Robertson, James S.; Kim, Denny; Hendry, Michael; Singh, Vidisha; Mac, Lisa M.; Chen, Robert T.

2016-01-01

In 2003 and 2013, the World Health Organization convened informal consultations on characterization and quality aspects of vaccines based on live virus vectors. In the resulting reports, one of several issues raised for future study was the potential for recombination of virus-vectored vaccines with wild type pathogenic virus strains. This paper presents an assessment of this issue formulated by the Brighton Collaboration. To provide an appropriate context for understanding the potential for recombination of virus-vectored vaccines, we review briefly the current status of virus vectored vaccines, mechanisms of recombination between viruses, experience with recombination involving live attenuated vaccines in the field, and concerns raised previously in the literature regarding recombination of virus-vectored vaccines with wild type virus strains. We then present a discussion of the major variables that could influence recombination between a virus-vectored vaccine and circulating wild type virus and the consequences of such recombination, including intrinsic recombination properties of the parent virus used as a vector; sequence relatedness of vector and wild virus; virus host range, pathogenesis and transmission; replication competency of vector in target host; mechanism of vector attenuation; additional factors potentially affecting virulence; and circulation of multiple recombinant vectors in the same target population. Finally, we present some guiding principles for vector design and testing intended to anticipate and mitigate the potential for and consequences of recombination of virus-vectored vaccines with wild type pathogenic virus strains. PMID:27346303

Exploratory biomarker analysis for treatment response in KRAS wild type metastatic colorectal cancer patients who received cetuximab plus irinotecan

International Nuclear Information System (INIS)

Kim, Seung Tae; Ahn, Tae Jin; Lee, Eunjin; Do, In-Gu; Lee, Su Jin; Park, Se Hoon; Park, Joon Oh; Park, Young Suk; Lim, Ho Yeong; Kang, Won Ki; Kim, Suk Hyeong; Lee, Jeeyun; Kim, Hee Cheol

2015-01-01

More than half of the patients selected based on KRAS mutation status fail to respond to the treatment with cetuximab in metastatic colorectal cancer (mCRC). We designed a study to identify additional biomarkers that could act as indicators for cetuximab treatment in mCRC. We investigated 58 tumor samples from wild type KRAS CRC patients treated with cetuximab plus irinotecan (CI). We conducted the genotyping for mutations in either BRAF or PIK3CA and profiled comprehensively the expression of 522 kinase genes. BRAF mutation was detected in 5.1 % (3/58) of patients. All 50 patients showed wild type PIK3CA. Gene expression patterns that categorized patients with or without the disease control to CI were compared by supervised classification analysis. PSKH1, TLK2 and PHKG2 were overexpressed significantly in patients with the disease control to IC. The higher expression value of PSKH1 (r = 0.462, p < 0.001) and TLK2 (r = 0.361, p = 0.005) had the significant correlation to prolonged PFS. The result of this work demonstrated that expression nature of kinase genes such as PSKH1, TLK2 and PHKG2 may be informative to predict the efficacy of CI in wild type KRAS CRC. Mutations in either BRAF or PIK3CA were rare subsets in wild type KRAS CRC

MLH1-deficient Colorectal Carcinoma With Wild-type BRAF and MLH1 Promoter Hypermethylation Harbor KRAS Mutations and Arise From Conventional Adenomas.

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Farchoukh, Lama; Kuan, Shih-Fan; Dudley, Beth; Brand, Randall; Nikiforova, Marina; Pai, Reetesh K

2016-10-01

Between 10% and 15% of colorectal carcinomas demonstrate sporadic DNA mismatch-repair protein deficiency as a result of MLH1 promoter methylation and are thought to arise from sessile serrated adenomas, termed the serrated neoplasia pathway. Although the presence of the BRAF V600E mutation is indicative of a sporadic cancer, up to 30% to 50% of colorectal carcinomas with MLH1 promoter hypermethylation will lack a BRAF mutation. We report the clinicopathologic and molecular features of MLH1-deficient colorectal carcinoma with wild-type BRAF and MLH1 promoter hypermethylation (referred to as MLH1-hypermethylated BRAF wild-type colorectal carcinoma, n=36) in comparison with MLH1-deficient BRAF-mutated colorectal carcinoma (n=113) and Lynch syndrome-associated colorectal carcinoma (n=36). KRAS mutations were identified in 31% of MLH1-hypermethylated BRAF wild-type colorectal carcinomas compared with 0% of MLH1-deficient BRAF-mutated colorectal carcinomas and 37% of Lynch syndrome-associated colorectal carcinomas. When a precursor polyp was identified, MLH1-hypermethylated BRAF wild-type colorectal carcinomas arose from precursor polyps resembling conventional tubular/tubulovillous adenomas in contrast to MLH1-deficient BRAF-mutated colorectal carcinomas, which arose from precursor sessile serrated adenomas (PMLH1-hypermethylated BRAF wild-type colorectal carcinoma and MLH1-deficient BRAF-mutated colorectal carcinoma had a predilection for the right colon compared with Lynch syndrome-associated colorectal carcinoma (86% vs. 92% vs. 49%, P0.05). In conclusion, our results indicate that MLH1-hypermethylated BRAF wild-type colorectal carcinomas can harbor KRAS mutations and arise from precursor polyps resembling conventional tubular/tubulovillous adenomas.

Mineral phosphate solubilization by wild type and radiation induced mutants of pantoea dispersa and pantoea terrae

International Nuclear Information System (INIS)

Murugesan, Senthilkumar; Lee, Young Keun; Kim, Jung Hun

2009-01-01

Three mineral phosphate solubilizing (MPS) bacteria where isolated from rhizosphere soil samples of common bean and weed plants. 16S rDNA analysis indicated that the isolate P2 and P3 are closely related to Pantoea dispersa while isolate P4 is closely related to Pantoea terrae. Islates P2 and P3 recorded 381.60 μg ml -1 of tricalcium phosphate (TCP) solubilization respectively on 3 days incubation. Isolate P4 recorded the TCP solubilization of 215.85 μg ml -1 and the pH was dropped to 4.44 on 24 h incubation. Further incubation of P4 sharply decreased the available phosphorous to 28.94 μg ml -1 and pH level was raised to 6.32. Gamma radiation induced mutagenesis was carried out at LD 99 dose of the wild type strains. The total of 14 mutant clones with enhanced MPS activity and 4 clones with decreased activity were selected based on solubilization index (SI) and phosphate solubilization assay. Mutant P2-M1 recorded the highest P-solubilizing potential among any other wild or mutnat clones by releasing 504.21 μg ml -1 of phosphorous i.e. 35% higher than its wild type by the end of day 5. A comparative evaluation of TCP solubilization by wild type isolates of Pantoea and their mutants, led to select three MPS mutant clones such as P2-M1, P3-M2 and P3-M4 with a potential to release >471.67 μg ml 1 of phosphorous from TCP. These over expressing mutant clones are considered as suitable candidates for biofertilization

MR imaging of cranial nerve schwannomas

International Nuclear Information System (INIS)

Shapiro, M.; Peyster, R.; Cross, R.R.; Charles, J.; Murtagh, R.; Shapiro, R.; Chyatte, D.

1988-01-01

One of the major advantages of magnetic resonance (MR) imaging over other imaging modalities is direct visualization of the cranial nerves. This is best accomplished with thin-section, contiguous T1-weighted images. They report a series of 75 cranial nerve neuromas, including 47 of the eighth nerve and a mixture of schwannomas involving all other cranial nerves (excluding the fourth). All tumors demonstrated at least some area of increased signal (equal to or greater than that of cerebrospinal fluid) on T2-weighted images. This fact enabled them to differentiate schwannomas from neoplasms (lymphoma, meningioma, sarcoma) that may be isointense on T2-weighted pulse sequences. Many of the lesions had areas of low signal intermixed with predominantly high signal (on T2-weighted images). The pathologic evaluation of these areas of decreased signal revealed predominant fibrosis. In addition, some of the neuromas had a cystic component. Gadolinium-enhanced MR imaging may permit detection when the nerve is still normal in size

Cranial involvement in sickle cell disease

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Alkan, Ozlem, E-mail: yalinozlem@hotmail.com [Department of Radiology, Faculty of Medicine, Baskent University, Ankara (Turkey); Kizilkilic, Ebru, E-mail: ebru90@yahoo.com [Department of Hematology, Faculty of Medicine, Baskent University, Ankara (Turkey); Kizilkilic, Osman, E-mail: ebos90@hotmail.com [Department of Radiology, Faculty of Medicine, Baskent University, Ankara (Turkey); Yildirim, Tulin, E-mail: ytulin@hotmail.com [Department of Radiology, Faculty of Medicine, Baskent University, Ankara (Turkey); Karaca, Sibel, E-mail: sibelkaraca@hotmail.com [Department of Neurology, Faculty of Medicine, Baskent University, Ankara (Turkey); Yeral, Mahmut, E-mail: mahmutyeral@hotmail.com [Department of Hematology, Faculty of Medicine, Baskent University, Ankara (Turkey); Kasar, Mutlu, E-mail: mutlukasar@hotmail.com [Department of Hematology, Faculty of Medicine, Baskent University, Ankara (Turkey); Ozdogu, Hakan, E-mail: hakanozdogu@hotmail.com [Department of Hematology, Faculty of Medicine, Baskent University, Ankara (Turkey)

2010-11-15

Purpose: To evaluate cranial findings in patients with neurologically symptomatic sickle cell disease (SCD). Materials and methods: We studied 50 consecutive patients with SCD and neurologic symptoms. All patients underwent brain MR examinations: all 50 underwent classic MR imaging; 42, diffusion-weighted MR imaging; 10, MR angiography; four, MR venography; and three patients, digital subtraction angiography. Results: Of the 50 SCD patients, 19 (38%) had normal MR findings, and 31 (62%) showed abnormalities on brain MR images. Of the 50 patients, 16 (32%) had ischemic lesions; two (4%), subarachnoid hemorrhage; one (2%), moya-moya pattern; one (2%), posterior reversible encephalopathy; one (2%), dural venous sinus thrombosis; 12 (24%), low marrow signal intensity and thickness of the diploic space; 12 (24%), cerebral atrophy; and two (4%), osteomyelitis. Twenty-seven patients (54%) presented with headache, which was the most common clinical finding. Conclusions: The cranial involvement is one of the most devastating complications of SCD. Early and accurate diagnosis is important in the management of cranial complications of SCD.

Fitness of crop-wild hybrid sunflower under competitive conditions: implications for crop-to-wild introgression.

Science.gov (United States)

Mercer, Kristin L; Emry, D Jason; Snow, Allison A; Kost, Matthew A; Pace, Brian A; Alexander, Helen M

2014-01-01

Understanding the likelihood and extent of introgression of novel alleles in hybrid zones requires comparison of lifetime fitness of parents and hybrid progeny. However, fitness differences among cross types can vary depending on biotic conditions, thereby influencing introgression patterns. Based on past work, we predicted that increased competition would enhance introgression between cultivated and wild sunflower (Helianthus annuus) by reducing fitness advantages of wild plants. To test this prediction, we established a factorial field experiment in Kansas, USA where we monitored the fitness of four cross types (Wild, F1, F2, and BCw hybrids) under different levels of interspecific and intraspecific competition. Intraspecific manipulations consisted both of density of competitors and of frequency of crop-wild hybrids. We recorded emergence of overwintered seeds, survival to reproduction, and numbers of seeds produced per reproductive plant. We also calculated two compound fitness measures: seeds produced per emerged seedling and seeds produced per planted seed. Cross type and intraspecific competition affected emergence and survival to reproduction, respectively. Further, cross type interacted with competitive treatments to influence all other fitness traits. More intense competition treatments, especially related to density of intraspecific competitors, repeatedly reduced the fitness advantage of wild plants when considering seeds produced per reproductive plant and per emerged seedling, and F2 plants often became indistinguishable from the wilds. Wild fitness remained superior when seedling emergence was also considered as part of fitness, but the fitness of F2 hybrids relative to wild plants more than quadrupled with the addition of interspecific competitors and high densities of intraspecific competitors. Meanwhile, contrary to prediction, lower hybrid frequency reduced wild fitness advantage. These results emphasize the importance of taking a full life cycle

Fitness of crop-wild hybrid sunflower under competitive conditions: implications for crop-to-wild introgression.

Directory of Open Access Journals (Sweden)

Kristin L Mercer

Full Text Available Understanding the likelihood and extent of introgression of novel alleles in hybrid zones requires comparison of lifetime fitness of parents and hybrid progeny. However, fitness differences among cross types can vary depending on biotic conditions, thereby influencing introgression patterns. Based on past work, we predicted that increased competition would enhance introgression between cultivated and wild sunflower (Helianthus annuus by reducing fitness advantages of wild plants. To test this prediction, we established a factorial field experiment in Kansas, USA where we monitored the fitness of four cross types (Wild, F1, F2, and BCw hybrids under different levels of interspecific and intraspecific competition. Intraspecific manipulations consisted both of density of competitors and of frequency of crop-wild hybrids. We recorded emergence of overwintered seeds, survival to reproduction, and numbers of seeds produced per reproductive plant. We also calculated two compound fitness measures: seeds produced per emerged seedling and seeds produced per planted seed. Cross type and intraspecific competition affected emergence and survival to reproduction, respectively. Further, cross type interacted with competitive treatments to influence all other fitness traits. More intense competition treatments, especially related to density of intraspecific competitors, repeatedly reduced the fitness advantage of wild plants when considering seeds produced per reproductive plant and per emerged seedling, and F2 plants often became indistinguishable from the wilds. Wild fitness remained superior when seedling emergence was also considered as part of fitness, but the fitness of F2 hybrids relative to wild plants more than quadrupled with the addition of interspecific competitors and high densities of intraspecific competitors. Meanwhile, contrary to prediction, lower hybrid frequency reduced wild fitness advantage. These results emphasize the importance of taking

Fitness of Crop-Wild Hybrid Sunflower under Competitive Conditions: Implications for Crop-to-Wild Introgression

Science.gov (United States)

Mercer, Kristin L.; Emry, D. Jason; Snow, Allison A.; Kost, Matthew A.; Pace, Brian A.; Alexander, Helen M.

2014-01-01

Understanding the likelihood and extent of introgression of novel alleles in hybrid zones requires comparison of lifetime fitness of parents and hybrid progeny. However, fitness differences among cross types can vary depending on biotic conditions, thereby influencing introgression patterns. Based on past work, we predicted that increased competition would enhance introgression between cultivated and wild sunflower (Helianthus annuus) by reducing fitness advantages of wild plants. To test this prediction, we established a factorial field experiment in Kansas, USA where we monitored the fitness of four cross types (Wild, F1, F2, and BCw hybrids) under different levels of interspecific and intraspecific competition. Intraspecific manipulations consisted both of density of competitors and of frequency of crop-wild hybrids. We recorded emergence of overwintered seeds, survival to reproduction, and numbers of seeds produced per reproductive plant. We also calculated two compound fitness measures: seeds produced per emerged seedling and seeds produced per planted seed. Cross type and intraspecific competition affected emergence and survival to reproduction, respectively. Further, cross type interacted with competitive treatments to influence all other fitness traits. More intense competition treatments, especially related to density of intraspecific competitors, repeatedly reduced the fitness advantage of wild plants when considering seeds produced per reproductive plant and per emerged seedling, and F2 plants often became indistinguishable from the wilds. Wild fitness remained superior when seedling emergence was also considered as part of fitness, but the fitness of F2 hybrids relative to wild plants more than quadrupled with the addition of interspecific competitors and high densities of intraspecific competitors. Meanwhile, contrary to prediction, lower hybrid frequency reduced wild fitness advantage. These results emphasize the importance of taking a full life cycle

A review of hedgehog signaling in cranial bone development

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Angel ePan

2013-04-01

Full Text Available During craniofacial development, the Hedgehog (HH signaling pathway is essential for mesodermal tissue patterning and differentiation. The Hedgehog family consists of three protein ligands: Sonic Hedgehog (SHH, Indian Hedgehog (IHH, and Desert Hedgehog (DHH, of which two are expressed in the craniofacial complex (IHH and SHH. Dysregulations in HH signaling are well documented to result in a wide range of craniofacial abnormalities, including holoprosencephaly, hypotelorism, and cleft lip/palate. Furthermore, mutations in HH effectors, co-receptors, and ciliary proteins result in skeletal and craniofacial deformities. Cranial suture morphogenesis is a delicate developmental process that requires control of cell commitment, proliferation and differentiation. This review focuses on both what is known and what remains unknown regarding HH signaling in cranial suture morphogenesis and intramembranous ossification. As demonstrated from murine studies, expression of both SHH and IHH is critical to the formation and fusion of the cranial sutures and calvarial ossification. SHH expression has been observed in the cranial suture mesenchyme and its precise function is not fully defined, although some postulate SHH to delay cranial suture fusion. IHH expression is mainly found on the osteogenic fronts of the calvarial bones, and functions to induce cell proliferation and differentiation. Unfortunately, neonatal lethality of deficient mice precludes a detailed examination of their postnatal calvarial phenotype. In summary, a number of basic questions are yet to be answered regarding domains of expression, developmental role, and functional overlap of HH morphogens in the calvaria. Nevertheless, SHH and IHH ligands are integral to cranial suture development and regulation of calvarial ossification. When HH signaling goes awry, the resultant suite of morphologic abnormalities highlights the important roles of HH signaling in cranial development.

Androgen action during male sex differentiation includes suppression of cranial suspensory ligament development

NARCIS (Netherlands)

J.M.A. Emmen (Judith); A. McLuskey; J.A. Grootegoed (Anton); A.O. Brinkmann (Albert)

1998-01-01

textabstractThe cranial suspensory ligament is located on the border of the cranial (mesonephric) mesentery in adult female mammals, which runs between the cranial pole of the internal genitalia and the dorsal abdominal wall. Absence of the cranial suspensory ligament

Traumatic superior orbital fissure syndrome: assessment of cranial nerve recovery in 33 cases.

Science.gov (United States)

Chen, Chien-Tzung; Wang, Theresa Y; Tsay, Pei-Kwei; Huang, Faye; Lai, Jui-Pin; Chen, Yu-Ray

2010-07-01

Superior orbital fissure syndrome is a rare complication that occurs in association with craniofacial trauma. The characteristics of superior orbital fissure syndrome are attributable to a constellation of cranial nerve III, IV, and VI palsies. This is the largest series describing traumatic superior orbital fissure syndrome that assesses the recovery of individual cranial nerve function after treatment. In a review from 1988 to 2002, 33 patients with superior orbital fissure syndrome were identified from 11,284 patients (0.3 percent) with skull and facial fractures. Severity of cranial nerve injury and functional recovery were evaluated by extraocular muscle movement. Patients were evaluated on average 6 days after initial injury, and average follow-up was 11.8 months. There were 23 male patients. The average age was 31 years. The major mechanism of injury was motorcycle accident (67 percent). Twenty-two received conservative treatment, five were treated with steroids, and six patients underwent surgical decompression of the superior orbital fissure. After initial injury, cranial nerve VI suffered the most damage, whereas cranial nerve IV sustained the least. In the first 3 months, recovery was greatest in cranial nerve VI. At 9 months, function was lowest in cranial nerve VI and highest in cranial nerve IV. Eight patients (24 percent) had complete recovery of all cranial nerves. Functional recovery of all cranial nerves reached a plateau at 6 months after trauma. Cranial nerve IV suffered the least injury, whereas cranial nerve VI experienced the most neurologic deficits. Cranial nerve palsies improved to their final recovery endpoints by 6 months. Surgical decompression is considered when there is evidence of bony compression of the superior orbital fissure.

Mathematical model of the SOS response regulation in wild-type Escherichia coli

International Nuclear Information System (INIS)

Aksenov, S.V.

1997-01-01

Regulation of the SOS response in Escherichia coli, which is a set of inducible cellular reactions introduced after DNA damage, is due to specific interaction of LexA and RecA proteins. LexA protein is a common repressor of the genes of the SOS system, and RecA protein, once transiently activated by the so-called SOS-inducing signal, promotes LexA protein destruction. We have described the SOS regulation by means of differential equations with regard to LexA and RecA concentrations elsewhere. The 'input' function for model equations is the level of the SOS-inducing signal against time. Here we present a means for calculating the concentration of single-stranded DNA (SOS-inducing signal) as a function of time in wild-type cells after ultraviolet irradiation. With model equations one can simulate kinetic curves of SOS regulatory proteins after DNA damage to survey the SOS response kinetics. Simulation of LexA protein kinetics agrees with experimental data. We compare simulated LexA kinetic curves in wild-type and uνr - mutant bacteria, which is useful in investigating the way uνrABC-dependent excision repair modulates the SOS response kinetics. Possible applications of the model to investigating various aspects of the SOS induction are discussed

21 CFR 882.4370 - Pneumatic cranial drill motor.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Pneumatic cranial drill motor. 882.4370 Section 882.4370 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... drill motor. (a) Identification. A pneumatic cranial drill motor is a pneumatically operated power...

Anti-amyloid-β-mediated positron emission tomography imaging in Alzheimer's disease mouse brains.

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Daniel McLean

Full Text Available Antibody-mediated imaging of amyloid β (Aβ in Alzheimer's disease (AD offers a promising strategy to detect and monitor specific Aβ species, such as oligomers, that have important pathological and therapeutic relevance. The major current limitation of antibodies as a diagnostic and imaging device is poor blood-brain-barrier permeability. A classical anti-Aβ antibody, 6E10, is modified with 10 kDa polyethylene glycol (PEG and a positron emitting isotope, Copper-64 (t(½ = 12.7 h, and intravenously delivered to the TgCRND8 mouse model of Alzheimer's disease. Modification of 6E10 with PEG (6E10-PEG increases accumulation of 6E10 in brain tissue in both TgCRND8 and wild type control animals. 6E10-PEG differentiates TgCRND8 animals from wild type controls using positron emission tomography (PET and provides a framework for using antibodies to detect pathology using non-invasive medical imaging techniques.

Dinosaur remains from the type Maastrichtian: An update

NARCIS (Netherlands)

Weishampel, David B.; Mulder, Eric W A; Dortangs, Rudi W.; Jagt, John W M; Jianu, Coralia Maria; Kuypers, Marcel M M; Peeters, Hans H G; Schulp, Anne S.

1999-01-01

Isolated cranial and post-cranial remains of hadrosaurid dinosaurs have been collected from various outcrops in the type area of the Maastrichtian stage during the last few years. In the present contribution, dentary and maxillary teeth are recorded from the area for the first time. Post-cranial

Sequence analysis of chromosome 1 revealed different selection patterns between Chinese wild mice and laboratory strains.

Science.gov (United States)

Xu, Fuyi; Hu, Shixian; Chao, Tianzhu; Wang, Maochun; Li, Kai; Zhou, Yuxun; Xu, Hongyan; Xiao, Junhua

2017-10-01

Both natural and artificial selection play a critical role in animals' adaptation to the environment. Detection of the signature of selection in genomic regions can provide insights for understanding the function of specific phenotypes. It is generally assumed that laboratory mice may experience intense artificial selection while wild mice more natural selection. However, the differences of selection signature in the mouse genome and underlying genes between wild and laboratory mice remain unclear. In this study, we used two mouse populations: chromosome 1 (Chr 1) substitution lines (C1SLs) derived from Chinese wild mice and mouse genome project (MGP) sequenced inbred strains and two selection detection statistics: Fst and Tajima's D to identify the signature of selection footprint on Chr 1. For the differentiation between the C1SLs and MGP, 110 candidate selection regions containing 47 protein coding genes were detected. A total of 149 selection regions which encompass 7.215 Mb were identified in the C1SLs by Tajima's D approach. While for the MGP, we identified nearly twice selection regions (243) compared with the C1SLs which accounted for 13.27 Mb Chr 1 sequence. Through functional annotation, we identified several biological processes with significant enrichment including seven genes in the olfactory transduction pathway. In addition, we searched the phenotypes associated with the 47 candidate selection genes identified by Fst. These genes were involved in behavior, growth or body weight, mortality or aging, and immune systems which align well with the phenotypic differences between wild and laboratory mice. Therefore, the findings would be helpful for our understanding of the phenotypic differences between wild and laboratory mice and applications for using this new mouse resource (C1SLs) for further genetics studies.

Arterial supply of the lower cranial nerves: a comprehensive review.

Science.gov (United States)

Hendrix, Philipp; Griessenauer, Christoph J; Foreman, Paul; Loukas, Marios; Fisher, Winfield S; Rizk, Elias; Shoja, Mohammadali M; Tubbs, R Shane

2014-01-01

The lower cranial nerves receive their arterial supply from an intricate network of tributaries derived from the external carotid, internal carotid, and vertebrobasilar territories. A contemporary, comprehensive literature review of the vascular supply of the lower cranial nerves was performed. The vascular supply to the trigeminal, facial, vestibulocochlear, glossopharyngeal, vagus, spinal accessory, and hypoglossal nerves are illustrated with a special emphasis on clinical issues. Frequently the external carotid, internal carotid, and vertebrobasilar territories all contribute to the vascular supply of an individual cranial nerve along its course. Understanding of the vasculature of the lower cranial nerves is of great relevance for skull base surgery. Copyright © 2013 Wiley Periodicals, Inc.

Imaging of muscular denervation secondary to motor cranial nerve dysfunction

International Nuclear Information System (INIS)

Connor, S.E.J.; Chaudhary, N.; Fareedi, S.; Woo, E.K.

2006-01-01

The effects of motor cranial nerve dysfunction on the computed tomography (CT) and magnetic resonance imaging (MRI) appearances of head and neck muscles are reviewed. Patterns of denervation changes are described and illustrated for V, VII, X, XI and XII cranial nerves. Recognition of the range of imaging manifestations, including the temporal changes in muscular appearances and associated muscular grafting or compensatory hypertrophy, will avoid misinterpretation as local disease. It will also prompt the radiologist to search for underlying cranial nerve pathology, which may be clinically occult. The relevant cranial nerve motor division anatomy will be described to enable a focussed search for such a structural abnormality

Imaging of muscular denervation secondary to motor cranial nerve dysfunction

Energy Technology Data Exchange (ETDEWEB)

Connor, S.E.J. [Neuroradiology Department, Kings College Hospital, Denmark Hill, London SE5 9RS (United Kingdom)]. E-mail: sejconnor@tiscali.co.uk; Chaudhary, N. [Neuroradiology Department, Kings College Hospital, Denmark Hill, London SE5 9RS (United Kingdom); Fareedi, S. [Neuroradiology Department, Kings College Hospital, Denmark Hill, London SE5 9RS (United Kingdom); Woo, E.K. [Neuroradiology Department, Kings College Hospital, Denmark Hill, London SE5 9RS (United Kingdom)

2006-08-15

The effects of motor cranial nerve dysfunction on the computed tomography (CT) and magnetic resonance imaging (MRI) appearances of head and neck muscles are reviewed. Patterns of denervation changes are described and illustrated for V, VII, X, XI and XII cranial nerves. Recognition of the range of imaging manifestations, including the temporal changes in muscular appearances and associated muscular grafting or compensatory hypertrophy, will avoid misinterpretation as local disease. It will also prompt the radiologist to search for underlying cranial nerve pathology, which may be clinically occult. The relevant cranial nerve motor division anatomy will be described to enable a focussed search for such a structural abnormality.

Normal social seeking behavior, hypoactivity and reduced exploratory range in a mouse model of Angelman syndrome

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Reiter Lawrence T

2011-01-01

Full Text Available Abstract Background Angelman syndrome (AS is a neurogenetic disorder characterized by severe developmental delay with mental retardation, a generally happy disposition, ataxia and characteristic behaviors such as inappropriate laughter, social-seeking behavior and hyperactivity. The majority of AS cases are due to loss of the maternal copy of the UBE3A gene. Maternal Ube3a deficiency (Ube3am-/p+, as well as complete loss of Ube3a expression (Ube3am-/p-, have been reproduced in the mouse model used here. Results Here we asked if two characteristic AS phenotypes - social-seeking behavior and hyperactivity - are reproduced in the Ube3a deficient mouse model of AS. We quantified social-seeking behavior as time spent in close proximity to a stranger mouse and activity as total time spent moving during exploration, movement speed and total length of the exploratory path. Mice of all three genotypes (Ube3am+/p+, Ube3am-/p+, Ube3am-/p- were tested and found to spend the same amount of time in close proximity to the stranger, indicating that Ube3a deficiency in mice does not result in increased social seeking behavior or social dis-inhibition. Also, Ube3a deficient mice were hypoactive compared to their wild-type littermates as shown by significantly lower levels of activity, slower movement velocities, shorter exploratory paths and a reduced exploratory range. Conclusions Although hyperactivity and social-seeking behavior are characteristic phenotypes of Angelman Syndrome in humans, the Ube3a deficient mouse model does not reproduce these phenotypes in comparison to their wild-type littermates. These phenotypic differences may be explained by differences in the size of the genetic defect as ~70% of AS patients have a deletion that includes several other genes surrounding the UBE3A locus.

Clavulanic acid production by the MMS 150 mutant obtained from wild type Streptomyces clavuligerus ATCC 27064

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Eliton da Silva Vasconcelos

2013-12-01

Full Text Available Clavulanic acid (CA is a powerful inhibitor of the beta-lactamases, enzymes produced by bacteria resistants to penicillin and cefalosporin. This molecule is produced industrially by strains of Streptomyces clavuligerus in complex media which carbon and nitrogen resources are supplied by inexpensive compounds still providing high productivity. The genetic production improvement using physical and chemical mutagenic agents is an important strategy in programs of industrial production development of bioactive metabolites. However, parental strains are susceptible to loss of their original productivity due genetic instability phenomenona. In this work, some S. clavuligerus mutant strains obtained by treatment with UV light and with MMS are compared with the wild type (Streptomyces clavuligerus ATCC 27064. The results indicated that the random mutations originated some strains with different phenotypes, most divergent demonstrated by the mutants strains named AC116, MMS 150 and MMS 54, that exhibited lack of pigmentation in their mature spores. Also, the strain MMS 150 presented a larger production of CA when cultivated in semi-synthetics media. Using other media, the wild type strain obtained a larger CA production. Besides, using the modifed complex media the MMS 150 strain showed changes in its lipolitic activity and a larger production of CA. The studies also allowed finding the best conditions for a lipase activity exhibited by wild type S. clavuligerus and the MMS150 mutant.

Clavulanic acid production by the MMS 150 mutant obtained from wild type Streptomyces clavuligerus ATCC 27064.

Science.gov (United States)

da Silva Vasconcelos, Eliton; de Lima, Vanderlei Aparecido; Goto, Leandro Seiji; Cruz-Hernández, Isara Lourdes; Hokka, Carlos Osamu

2013-12-01

Clavulanic acid (CA) is a powerful inhibitor of the beta-lactamases, enzymes produced by bacteria resistants to penicillin and cefalosporin. This molecule is produced industrially by strains of Streptomyces clavuligerus in complex media which carbon and nitrogen resources are supplied by inexpensive compounds still providing high productivity. The genetic production improvement using physical and chemical mutagenic agents is an important strategy in programs of industrial production development of bioactive metabolites. However, parental strains are susceptible to loss of their original productivity due genetic instability phenomenona. In this work, some S. clavuligerus mutant strains obtained by treatment with UV light and with MMS are compared with the wild type (Streptomyces clavuligerus ATCC 27064). The results indicated that the random mutations originated some strains with different phenotypes, most divergent demonstrated by the mutants strains named AC116, MMS 150 and MMS 54, that exhibited lack of pigmentation in their mature spores. Also, the strain MMS 150 presented a larger production of CA when cultivated in semi-synthetics media. Using other media, the wild type strain obtained a larger CA production. Besides, using the modifed complex media the MMS 150 strain showed changes in its lipolitic activity and a larger production of CA. The studies also allowed finding the best conditions for a lipase activity exhibited by wild type S. clavuligerus and the MMS150 mutant.

Forming a complex with MHC class I molecules interferes with mouse CD1d functional expression.

Directory of Open Access Journals (Sweden)

Renukaradhya J Gourapura

Full Text Available CD1d molecules are structurally similar to MHC class I, but present lipid antigens as opposed to peptides. Here, we show that MHC class I molecules physically associate with (and regulate the functional expression of mouse CD1d on the surface of cells. Low pH (3.0 acid stripping of MHC class I molecules resulted in increased surface expression of murine CD1d on antigen presenting cells as well as augmented CD1d-mediated antigen presentation to NKT cells. Consistent with the above results, TAP1-/- mice were found to have a higher percentage of type I NKT cells as compared to wild type mice. Moreover, bone marrow-derived dendritic cells from TAP1-/- mice showed increased antigen presentation by CD1d compared to wild type mice. Together, these results suggest that MHC class I molecules can regulate NKT cell function, in part, by masking CD1d.

The role of prophylactic cranial irradiation in small cell lung cancer

International Nuclear Information System (INIS)

Kiricuta, I.C.; Bohndorf, W.

1996-01-01

To analyse if prophylactic cranial irradiation is small cell lung cancer for improved survival is indicated; if adjuvant irradiation could cure the microscopic disease; if and how late effects could be minimized. Data from randomized trials and retrospective studies are critically analysed related to the incidence of central nervous system (CNS) metastases in limited disease patients in complete remission with or without prophylactic cranial irradiation. The mechanisms of late effects on CNS of prophylactic cranial irradiation and combined treatment are presented. Prophylactic cranial irradiation could decrease the incidence of CNS metastases but could not improve survival. A subgroup of patients (9 to 14%) most likely to benefit from prophylactic cranial irradiation includes patients who are likely to have an isolated CNS failure. The actual used total dose in the range 30 to 40 Gy could only conditionally decrease the CNS failure. Higher total and/or daily doses and combined treatment are related with potentially devastating neurologic and intellectual disabilities. No prospective randomized trial has demonstrated a significant survival advantage for patients treated with prophylactic cranial irradiation. Prophylactic cranial irradiation is capable of reducing the incidence of cerebral metastases and delays CNS failure. A subgroup of patients most likely to benefit from prophylactic cranial irradiation (9 to 14%) includes patients who are likely to have an isolated CNS failure, but this had yet to be demonstrated. The toxicity of treatment is difficult to be influenced. Prophylactic cranial irradiation should not be given concurrently with chemotherapy, a larger interval after chemotherapy is indicated. The total dose should be in the range 30 to 36 Gy and the daily fraction size not larger than 2 Gy. (orig.) [de

Evaluation of paracavernous cranial nerves (3rd to 6th) with CT

International Nuclear Information System (INIS)

Tsuha, Mitsuru; Okamura, Tomomi; Abiko, Seisho; Aoki, Hideo

1984-01-01

We have now used CT to evaluate the cavernous sinuses, especially the 3rd, 4th, 5th, and 6th cranial nerves. adjacent to them. Twenty cases, presumably all having sellar or parasellar lesions, were examined by means of thin-slice (2-4 mm) axial and coronal (including both direct and reconstructed methods) CT studies. Moreover, three blocks of the sellar region obtained from adult cadavers were examined beforehand by CT scan, and the courses of the respective paracavernous cranial nerves were confirmed by microsurgical dissection. As a result, the following conclusions were obtained. 1. It was valuable to perform a post-enhanced direct coronal study for the definite identification of the paracavernous cranial nerves (3rd to 6th cranial nerves). 2. Also valuable was a magnified CT film of the parasellar regions, which made the identification of the parasellar cranial nerves clearer. 3. In the clinical cases showing a normal shape of the cavernous sinuses on CT, each cranial nerve was evaluated. In the axial studies (almost 10 to 15 degrees anterior to Reid's basal line), the frequencies of the identification of the 3rd, 5th, and 6th cranial nerves were 76%, 97% (as to the Gasserian ganglion), and 21% respectively. None of the 4th cranial nerve was visualized in the cases examined. On the other hand, the frequencies of the identification of the 3rd, 5th, and 6th cranial nerves were 83%, 86%, and 21% respectively in the direct coronal studies and 62%, 57%, and 4% in those of the reconstructed films. The visualization of each cranial nerve in the direct coronal study was better than when the reconstructed method was used. Finally, a schematic presentation of the cranial nerves adjacent to the cavernous sinuses was made in the axial and coronal projections. (J.P.N.)

Decreased anxiety- and depression-like behaviors and hyperactivity in a type 3 deiodinase-deficient mouse showing brain thyrotoxicosis and peripheral hypothyroidism.

Science.gov (United States)

Stohn, J Patrizia; Martinez, M Elena; Hernandez, Arturo

2016-12-01

Hypo- and hyperthyroid states, as well as functional abnormalities in the hypothalamic-pituitary-thyroid axis have been associated with psychiatric conditions like anxiety and depression. However, the nature of this relationship is poorly understood since it is difficult to ascertain the thyroid status of the brain in humans. Data from animal models indicate that the brain exhibits efficient homeostatic mechanisms that maintain local levels of the active thyroid hormone, triiodothyronine (T3) within a narrow range. To better understand the consequences of peripheral and central thyroid status for mood-related behaviors, we used a mouse model of type 3 deiodinase (DIO3) deficiency (Dio3 -/- mouse). This enzyme inactivates thyroid hormone and is highly expressed in the adult central nervous system. Adult Dio3 -/- mice exhibit elevated levels of T3-dependent gene expression in the brain, despite peripheral hypothyroidism as indicated by low circulating levels of thyroxine and T3. Dio3 -/- mice of both sexes exhibit hyperactivity and significantly decreased anxiety-like behavior, as measured by longer time spent in the open arms of the elevated plus maze and in the light area of the light/dark box. During the tail suspension, they stayed immobile for a significantly shorter time than their wild-type littermates, suggesting decreased depression-like behavior. These results indicate that increased thyroid hormone in the brain, not necessarily in peripheral tissues, correlates with hyperactivity and with decreases in anxiety and depression-like behaviors. Our results also underscore the importance of DIO3 as a determinant of behavior by locally regulating the brain levels of thyroid hormone. Copyright © 2016 Elsevier Ltd. All rights reserved.

ADAM10 is essential for cranial neural crest-derived maxillofacial bone development

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Tan, Yu, E-mail: tanyu2048@163.com; Fu, Runqing, E-mail: furunqing@sjtu.edu.cn; Liu, Jiaqiang, E-mail: liujqmj@163.com; Wu, Yong, E-mail: wyonger@gmail.com; Wang, Bo, E-mail: wb228@126.com; Jiang, Ning, E-mail: 179639060@qq.com; Nie, Ping, E-mail: nieping1011@sina.com; Cao, Haifeng, E-mail: 0412chf@163.com; Yang, Zhi, E-mail: wcums1981@163.com; Fang, Bing, E-mail: fangbing@sjtu.edu.cn

2016-07-08

Growth disorders of the craniofacial bones may lead to craniofacial deformities. The majority of maxillofacial bones are derived from cranial neural crest cells via intramembranous bone formation. Any interruption of the craniofacial skeleton development process might lead to craniofacial malformation. A disintegrin and metalloprotease (ADAM)10 plays an essential role in organ development and tissue integrity in different organs. However, little is known about its function in craniofacial bone formation. Therefore, we investigated the role of ADAM10 in the developing craniofacial skeleton, particularly during typical mandibular bone development. First, we showed that ADAM10 was expressed in a specific area of the craniofacial bone and that the expression pattern dynamically changed during normal mouse craniofacial development. Then, we crossed wnt1-cre transgenic mice with adam10-flox mice to generate ADAM10 conditional knockout mice. The stereomicroscopic, radiographic, and von Kossa staining results showed that conditional knockout of ADAM10 in cranial neural crest cells led to embryonic death, craniofacial dysmorphia and bone defects. Furthermore, we demonstrated that impaired mineralization could be triggered by decreased osteoblast differentiation, increased cell death. Overall, these findings show that ADAM10 plays an essential role in craniofacial bone development. -- Highlights: •We firstly reported that ADAM10 was essentially involved in maxillofacial bone development. •ADAM10 cKO mice present craniofacial dysmorphia and bone defects. •Impaired osteoblast differentiation,proliferation and apoptosis underlie the bone deformity.

ADAM10 is essential for cranial neural crest-derived maxillofacial bone development

International Nuclear Information System (INIS)

Tan, Yu; Fu, Runqing; Liu, Jiaqiang; Wu, Yong; Wang, Bo; Jiang, Ning; Nie, Ping; Cao, Haifeng; Yang, Zhi; Fang, Bing

2016-01-01

Growth disorders of the craniofacial bones may lead to craniofacial deformities. The majority of maxillofacial bones are derived from cranial neural crest cells via intramembranous bone formation. Any interruption of the craniofacial skeleton development process might lead to craniofacial malformation. A disintegrin and metalloprotease (ADAM)10 plays an essential role in organ development and tissue integrity in different organs. However, little is known about its function in craniofacial bone formation. Therefore, we investigated the role of ADAM10 in the developing craniofacial skeleton, particularly during typical mandibular bone development. First, we showed that ADAM10 was expressed in a specific area of the craniofacial bone and that the expression pattern dynamically changed during normal mouse craniofacial development. Then, we crossed wnt1-cre transgenic mice with adam10-flox mice to generate ADAM10 conditional knockout mice. The stereomicroscopic, radiographic, and von Kossa staining results showed that conditional knockout of ADAM10 in cranial neural crest cells led to embryonic death, craniofacial dysmorphia and bone defects. Furthermore, we demonstrated that impaired mineralization could be triggered by decreased osteoblast differentiation, increased cell death. Overall, these findings show that ADAM10 plays an essential role in craniofacial bone development. -- Highlights: •We firstly reported that ADAM10 was essentially involved in maxillofacial bone development. •ADAM10 cKO mice present craniofacial dysmorphia and bone defects. •Impaired osteoblast differentiation,proliferation and apoptosis underlie the bone deformity.

White and Gray Matter Abnormalities After Cranial Radiation in Children and Mice

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Nieman, Brian J., E-mail: brian.nieman@utoronto.ca [Department of Physiology & Experimental Medicine, Hospital for Sick Children, Toronto, Ontario (Canada); Department of Medical Biophysics, University of Toronto, Toronto, Ontario (Canada); Ontario Institute for Cancer Research, Toronto, Ontario (Canada); Guzman, A. Elizabeth de [Department of Physiology & Experimental Medicine, Hospital for Sick Children, Toronto, Ontario (Canada); Department of Medical Biophysics, University of Toronto, Toronto, Ontario (Canada); Gazdzinski, Lisa M. [Department of Physiology & Experimental Medicine, Hospital for Sick Children, Toronto, Ontario (Canada); Lerch, Jason P. [Department of Neurosciences & Mental Health, Hospital for Sick Children, Toronto, Ontario (Canada); Department of Medical Biophysics, University of Toronto, Toronto, Ontario (Canada); Chakravarty, M. Mallar [Cerebral Imaging Centre, Douglas Mental Health University Institute, Montreal, Quebec (Canada); Departments of Psychiatry and Biomedical Engineering, McGill University, Montreal, Quebec (Canada); Pipitone, Jon [Kimel Family Translational Imaging Genetics Research Laboratory, Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Ontario (Canada); Strother, Douglas [Alberta Children' s Hospital, Calgary, Alberta (Canada); Departments of Oncology and Pediatrics, University of Calgary, Calgary, Alberta (Canada); Fryer, Chris [Division of Oncology/Hematology/BMT British Columbia Children' s Hospital and British Columbia Women' s Hospital and Health Centre, Vancouver, British Columbia (Canada); Department of Pediatrics, University of British Columbia, Vancouver, British Columbia (Canada); Bouffet, Eric [Department of Physiology & Experimental Medicine, Hospital for Sick Children, Toronto, Ontario (Canada); Department of Paediatrics, University of Toronto, Toronto, Ontario (Canada); and others

2015-11-15

Purpose: Pediatric patients treated with cranial radiation are at high risk of developing lasting cognitive impairments. We sought to identify anatomical changes in both gray matter (GM) and white matter (WM) in radiation-treated patients and in mice, in which the effect of radiation can be isolated from other factors, the time course of anatomical change can be established, and the effect of treatment age can be more fully characterized. Anatomical results were compared between species. Methods and Materials: Patients were imaged with T{sub 1}-weighted magnetic resonance imaging (MRI) after radiation treatment. Nineteen radiation-treated patients were divided into groups of 7 years of age and younger (7−) and 8 years and older (8+) and were compared to 41 controls. C57BL6 mice were treated with radiation (n=52) or sham treated (n=52) between postnatal days 16 and 36 and then assessed with in vivo and/or ex vivo MRI. In both cases, measurements of WM and GM volume, cortical thickness, area and volume, and hippocampal volume were compared between groups. Results: WM volume was significantly decreased following treatment in 7− and 8+ treatment groups. GM volume was unchanged overall, but cortical thickness was slightly increased in the 7− group. Results in mice mostly mirrored these changes and provided a time course of change, showing early volume loss and normal growth. Hippocampal volume showed a decreasing trend with age in patients, an effect not observed in the mouse hippocampus but present in the olfactory bulb. Conclusions: Changes in mice treated with cranial radiation are similar to those in humans, including significant WM and GM alterations. Because mice did not receive any other treatment, the similarity across species supports the expectation that radiation is causative and suggests mice provide a representative model for studying impaired brain development after cranial radiation and testing novel treatments.

White and Gray Matter Abnormalities After Cranial Radiation in Children and Mice

International Nuclear Information System (INIS)

Nieman, Brian J.; Guzman, A. Elizabeth de; Gazdzinski, Lisa M.; Lerch, Jason P.; Chakravarty, M. Mallar; Pipitone, Jon; Strother, Douglas; Fryer, Chris; Bouffet, Eric

2015-01-01

Purpose: Pediatric patients treated with cranial radiation are at high risk of developing lasting cognitive impairments. We sought to identify anatomical changes in both gray matter (GM) and white matter (WM) in radiation-treated patients and in mice, in which the effect of radiation can be isolated from other factors, the time course of anatomical change can be established, and the effect of treatment age can be more fully characterized. Anatomical results were compared between species. Methods and Materials: Patients were imaged with T_1-weighted magnetic resonance imaging (MRI) after radiation treatment. Nineteen radiation-treated patients were divided into groups of 7 years of age and younger (7−) and 8 years and older (8+) and were compared to 41 controls. C57BL6 mice were treated with radiation (n=52) or sham treated (n=52) between postnatal days 16 and 36 and then assessed with in vivo and/or ex vivo MRI. In both cases, measurements of WM and GM volume, cortical thickness, area and volume, and hippocampal volume were compared between groups. Results: WM volume was significantly decreased following treatment in 7− and 8+ treatment groups. GM volume was unchanged overall, but cortical thickness was slightly increased in the 7− group. Results in mice mostly mirrored these changes and provided a time course of change, showing early volume loss and normal growth. Hippocampal volume showed a decreasing trend with age in patients, an effect not observed in the mouse hippocampus but present in the olfactory bulb. Conclusions: Changes in mice treated with cranial radiation are similar to those in humans, including significant WM and GM alterations. Because mice did not receive any other treatment, the similarity across species supports the expectation that radiation is causative and suggests mice provide a representative model for studying impaired brain development after cranial radiation and testing novel treatments.

The effects of cervical traction, cranial rhythmic impulse, and Mckenzie exercise on headache and cervical muscle stiffness in episodic tension-type headache patients.

Science.gov (United States)

Choi, Sung-Yong; Choi, Jung-Hyun

2016-03-01

[Purpose] The purpose of this study was to examine the effects of cervical traction treatment, cranial rhythmic impulse treatment, a manual therapy, and McKenzie exercise, a dynamic strengthening exercise, on patients who have the neck muscle stiffness of the infrequent episodic tension-type (IETTH) headache and frequent episodic tension-type headache(FETTH), as well as to provide the basic materials for clinical interventions. [Subjects] Twenty-seven subjects (males: 15, females: 12) who were diagnosed with IETTH and FETTH after treatment by a neurologist were divided into three groups: (a cervical traction group (CTG, n=9), a cranial rhythmic contractiongroup (CRIG, n=9), and a McKenzie exercise group (MEG, n=9). An intervention was conducted for each group and the differences in their degrees of neck pain and changes in muscle tone were observed. [Results] In the within-group comparison of each group, headache significantly decreased in CTG. According to the results of the analysis of the muscle tone of the upper trapezius, there was a statistically significant difference in MEG on the right side and in CRIG on the left side. According to the results of the analysis of the muscle tone of the sternocleidomastoid muscle, there was a statistically significant difference in MEG on the right side and in CRIG on the left side. [Conclusion] In the comparison of the splenius capitis muscle between the groups, there was a statistically significant difference on the right side. Hence, compared to the other methods, cervical traction is concluded to be more effective at reducing headaches in IETTH and FETTH patients.

Development of a Human Cranial Bone Surrogate for Impact Studies

International Nuclear Information System (INIS)

Roberts, Jack C.; Merkle, Andrew C.; Carneal, Catherine M.; Voo, Liming M.; Johannes, Matthew S.; Paulson, Jeff M.; Tankard, Sara; Uy, O. Manny

2013-01-01

In order to replicate the fracture behavior of the intact human skull under impact it becomes necessary to develop a material having the mechanical properties of cranial bone. The most important properties to replicate in a surrogate human skull were found to be the fracture toughness and tensile strength of the cranial tables as well as the bending strength of the three-layer (inner table-diplöe-outer table) architecture of the human skull. The materials selected to represent the surrogate cranial tables consisted of two different epoxy resins systems with random milled glass fiber to enhance the strength and stiffness and the materials to represent the surrogate diplöe consisted of three low density foams. Forty-one three-point bending fracture toughness tests were performed on nine material combinations. The materials that best represented the fracture toughness of cranial tables were then selected and formed into tensile samples and tested. These materials were then used with the two surrogate diplöe foam materials to create the three-layer surrogate cranial bone samples for three-point bending tests. Drop tower tests were performed on flat samples created from these materials and the fracture patterns were very similar to the linear fractures in pendulum impacts of intact human skulls, previously reported in the literature. The surrogate cranial tables had the quasi-static fracture toughness and tensile strength of 2.5 MPa√ m and 53 ± 4.9 MPa, respectively, while the same properties of human compact bone were 3.1 ± 1.8 MPa√ m and 68 ± 18 MPa, respectively. The cranial surrogate had a quasi-static bending strength of 68 ± 5.7 MPa, while that of cranial bone was 82 ± 26 MPa. This material/design is currently being used to construct spherical shell samples for drop tower and ballistic tests.

Phosphorylated EGFR expression may predict outcome of EGFR-TKIs therapy for the advanced NSCLC patients with wild-type EGFR

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Wang Fen

2012-08-01

Full Text Available Abstract Background EGFR mutation is a strong predictive factor of EGFR-TKIs therapy. However, at least 10% of patients with EGFR wild-type are responsive to TKIs, suggesting that other determinants of outcome besides EGFR mutation might exist. We hypothesized that activation of phosphorylated EGFR could be a potential predictive biomarker to EGFR-TKIs treatment among patients in wild-type EGFR. Method Total of 205 stage IIIb and IV NSCLC patients, tissue samples of whom were available for molecular analysis, were enrolled in this study. The phosphorylation of EGFR at tyrosine 1068 (pTyr1068 and 1173 (pTyr1173 were assessed by immunohistochemistry, and EGFR mutations were detected by denaturing high performance liquid chromatograph (DHPLC. Results Among 205 patients assessable for EGFR mutation and phosphorylation analysis, 92 (44.9% were EGFR mutant and 165 patients (57.6% had pTyr1173 expression. Superior progression-free survival (PFS was seen after EGFR-TKIs therapy in patients with pTyr1068 expression compared to pTyr1068 negative ones (median PFS 7.0 months vs. 1.2 months, P P = 0.016. In subgroup of patients with wild-type EGFR, pTyr1068 expression positive ones had a significantly prolonged PFS (4.2 months vs.1.2 months P  Conclusion pTyr1068 may be a predictive biomarker for screening the population for clinical response to EGFR-TKIs treatment; especially for patients with wild-type EGFR.

p53-dependent manner of persistent activation of the radiation-induced reversion in the pink-eyed unstable mouse embryo

International Nuclear Information System (INIS)

Shiraishi, K.; Yonezawa, M.; Niwa, O.

2003-01-01

Full text: We previously reported that radiation has an ability to induce genomic instability which causes delayed and untargeted mutation. These mutations aren't accounted for by the usual relationship between DNA damages and repair. However, the mechanisms of a long-term memory of DNA damage and the persistence of up-regulated recombination activity have yet to be elucidated. The mouse pink-eyed unstable (pun) mutation is due to an intragenic duplication of the pink-eyed dilution locus and frequently reverts black to the wild type in germ cells as well as somatic cells. The frequency of reversion was estimated by counting cluster of pigment cells in retinal pigment epithelium. Twice increase of the reversion was observed in F1 mice born to 6Gy irradiated male at spermatozoa stage, but not at other spermatogenesis stages( -tid, -cyte, -gonia ). Trans-genarational effect in F2 mice also didn't observe. Therefore, this phenomenon only occurs under the restricted germ cell stage. Additionally, the reversion frequency of p53 deficient F1 mouse born to irradiated sperm was less than irradiated wild mouse. 5aza-dc chemical agent, which is DNA methylation emzyme inhibitor, also suppressed pun allele recombination in mouse embryo. These data indicate that p53 contributes delayed and untargeted mutation, perhaps, by regulation of DNA metylation status

Multiple Cranial Nerve Palsy Due to Cerebral Venous Thrombosis

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Esra Eruyar

2017-04-01

Full Text Available Cerebral venous thrombosis (CVT is a rare clinical condition between cerebrovasculer diases. The most common findings are headache, seizure and focal neurological deficit. Multiple cranial nerve palsy due to CVT is rarely seen and it is not clear pathology. A pathology that could explain the lack of cranial nerve imaging is carrying suspected diagnosis but the disease is known to provide early diagnosis and treatment. We want to emphasize with this case multipl cranial nerve palsy due to CVT is seen rarely and good response to treatment.

Is phenytoin contraindicated in patients receiving cranial irradiation?

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Borg, M.F. [Royal Adelaide Hospital, SA (Australia); Probert, J.C. [Auckland Hospital, Auckland (New Zealand). Dept. of Radiation Oncology; Zwi, L.J. [Auckland Univ. (New Zealand). Dept. of Medicine and Surgery

1995-02-01

Three recent publications have reported the development of erythema multiforme and Stevens-Johnson syndrome in patients receiving cranial irradiation and sodium phenytoin. Some authors have recommended that patients receiving whole brain radiation therapy and who have had seizures should not be prescribed phenytoin but an alternative anticonvulsant. This article reviews the current literature pertaining to the development of this potentially lethal complication in patients receiving whole brain radiation and phenytoin, with reference to the single recorded case of Stevens-Johnson syndrome in a patient receiving cranial irradiation and phenytoin in Auckland, New Zealand. While the clinical picture in the 16 patients reported in the literature and the current case report differed from the classical form of erythema multiforme, a similar pattern of presentation and outcome appeared in all patients reviewed, suggesting that the combination of phenytoin, cranial irradiation and the gradual reduction of concomitant steroids seem to lead to the development of erythema multiforme and/or Stevens-Johnson syndrome. The data presented, although sparse, suggest that phenytoin should not be prescribed in patients receiving cranial irradiation. 21 refs., 2 tabs., 3 figs.

Is phenytoin contraindicated in patients receiving cranial irradiation?

International Nuclear Information System (INIS)

Borg, M.F.; Probert, J.C.; Zwi, L.J.

1995-01-01

Three recent publications have reported the development of erythema multiforme and Stevens-Johnson syndrome in patients receiving cranial irradiation and sodium phenytoin. Some authors have recommended that patients receiving whole brain radiation therapy and who have had seizures should not be prescribed phenytoin but an alternative anticonvulsant. This article reviews the current literature pertaining to the development of this potentially lethal complication in patients receiving whole brain radiation and phenytoin, with reference to the single recorded case of Stevens-Johnson syndrome in a patient receiving cranial irradiation and phenytoin in Auckland, New Zealand. While the clinical picture in the 16 patients reported in the literature and the current case report differed from the classical form of erythema multiforme, a similar pattern of presentation and outcome appeared in all patients reviewed, suggesting that the combination of phenytoin, cranial irradiation and the gradual reduction of concomitant steroids seem to lead to the development of erythema multiforme and/or Stevens-Johnson syndrome. The data presented, although sparse, suggest that phenytoin should not be prescribed in patients receiving cranial irradiation. 21 refs., 2 tabs., 3 figs

Cranial vasculature in zebrafish forms by angioblast cluster-derived angiogenesis.

Science.gov (United States)

Proulx, Kira; Lu, Annie; Sumanas, Saulius

2010-12-01

Formation of embryonic vasculature involves vasculogenesis as endothelial cells differentiate and aggregate into vascular cords and angiogenesis which includes branching from the existing vessels. In the zebrafish which has emerged as an advantageous model to study vasculogenesis, cranial vasculature is thought to originate by a combination of vasculogenesis and angiogenesis, but how these processes are coordinated is not well understood. To determine how angioblasts assemble into cranial vasculature, we generated an etsrp:GFP transgenic line in which GFP reporter is expressed under the promoter control of an early regulator of vascular and myeloid development, etsrp/etv2. By utilizing time-lapse imaging we show that cranial vessels originate by angiogenesis from angioblast clusters, which themselves form by the mechanism of vasculogenesis. The two major pairs of bilateral clusters include the rostral organizing center (ROC) which gives rise to the most rostral cranial vessels and the midbrain organizing center (MOC) which gives rise to the posterior cranial vessels and to the myeloid and endocardial lineages. In Etsrp knockdown embryos initial cranial vasculogenesis proceeds normally but endothelial and myeloid progenitors fail to initiate differentiation, migration and angiogenesis. Such angioblast cluster-derived angiogenesis is likely to be involved during vasculature formation in other vertebrate systems as well. Copyright © 2010 Elsevier Inc. All rights reserved.

Histological and reference system for the analysis of mouse intervertebral disc.

Science.gov (United States)

Tam, Vivian; Chan, Wilson C W; Leung, Victor Y L; Cheah, Kathryn S E; Cheung, Kenneth M C; Sakai, Daisuke; McCann, Matthew R; Bedore, Jake; Séguin, Cheryle A; Chan, Danny

2018-01-01

A new scoring system based on histo-morphology of mouse intervertebral disc (IVD) was established to assess changes in different mouse models of IVD degeneration and repair. IVDs from mouse strains of different ages, transgenic mice, or models of artificially induced IVD degeneration were assessed. Morphological features consistently observed in normal, and early/later stages of degeneration were categorized into a scoring system focused on nucleus pulposus (NP) and annulus fibrosus (AF) changes. "Normal NP" exhibited a highly cellularized cell mass that decreased with natural ageing and in disc degeneration. "Normal AF" consisted of distinct concentric lamellar structures, which was disrupted in severe degeneration. NP/AF clefts indicated more severe changes. Consistent scores were obtained between experienced and new users. Altogether, our scoring system effectively differentiated IVD changes in various strains of wild-type and genetically modified mice and in induced models of IVD degeneration, and is applicable from the post-natal stage to the aged mouse. This scoring tool and reference resource addresses a pressing need in the field for studying IVD changes and cross-study comparisons in mice, and facilitates a means to normalize mouse IVD assessment between different laboratories. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:233-243, 2018. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

EBI3 regulates the NK cell response to mouse cytomegalovirus infection

DEFF Research Database (Denmark)

Jensen, Helle; Chen, Shih-Yu; Folkersen, Lasse Westergaard

2017-01-01

Natural killer (NK) cells are key mediators in the control of cytomegalovirus infection. Here, we show that Epstein-Barr virus-induced 3 (EBI3) is expressed by human NK cells after NKG2D or IL-12 plus IL-18 stimulation and by mouse NK cells during mouse cytomegalovirus (MCMV) infection. The induc......Natural killer (NK) cells are key mediators in the control of cytomegalovirus infection. Here, we show that Epstein-Barr virus-induced 3 (EBI3) is expressed by human NK cells after NKG2D or IL-12 plus IL-18 stimulation and by mouse NK cells during mouse cytomegalovirus (MCMV) infection....... The induction of EBI3 protein expression in mouse NK cells is a late activation event. Thus, early activation events of NK cells, such as IFNγ production and CD69 expression, were not affected in EBI3-deficient (Ebi3-/-) C57BL/6 (B6) mice during MCMV infection. Furthermore, comparable levels of early viral...... replication in spleen and liver were observed in MCMV-infected Ebi3-/- and wild-type (WT) B6 mice. Interestingly, the viral load in salivary glands and oral lavage was strongly decreased in the MCMV-infected Ebi3-/- B6 mice, suggesting that EBI3 plays a role in the establishment of MCMV latency. We detected...

Purkinje Cell Compartmentation in the Cerebellum of the Lysosomal Acid Phosphatase 2 Mutant Mouse (Nax - Naked-Ataxia Mutant Mouse)

Science.gov (United States)

Bailey, Karen; Rahimi Balaei, Maryam; Mannan, Ashraf; Del Bigio, Marc R.; Marzban, Hassan

2014-01-01

The Acp2 gene encodes the beta subunit of lysosomal acid phosphatase, which is an isoenzyme that hydrolyzes orthophosphoric monoesters. In mice, a spontaneous mutation in Acp2 results in severe cerebellar defects. These include a reduced size, abnormal lobulation, and an apparent anterior cerebellar disorder with an absent or hypoplastic vermis. Based on differential gene expression in the cerebellum, the mouse cerebellar cortex can normally be compartmentalized anteroposteriorly into four transverse zones and mediolaterally into parasagittal stripes. In this study, immunohistochemistry was performed using various Purkinje cell compartmentation markers to examine their expression patterns in the Acp2 mutant. Despite the abnormal lobulation and anterior cerebellar defects, zebrin II and PLCβ4 showed similar expression patterns in the nax mutant and wild type cerebellum. However, fewer stripes were found in the anterior zone of the nax mutant, which could be due to a lack of Purkinje cells or altered expression of the stripe markers. HSP25 expression was uniform in the central zone of the nax mutant cerebellum at around postnatal day (P) 18–19, suggesting that HSP25 immunonegative Purkinje cells are absent or delayed in stripe pattern expression compared to the wild type. HSP25 expression became heterogeneous around P22–23, with twice the number of parasagittal stripes in the nax mutant compared to the wild type. Aside from reduced size and cortical disorganization, both the posterior zone and nodular zone in the nax mutant appeared less abnormal than the rest of the cerebellum. From these results, it is evident that the anterior zone of the nax mutant cerebellum is the most severely affected, and this extends beyond the primary fissure into the rostral central zone/vermis. This suggests that ACP2 has critical roles in the development of the anterior cerebellum and it may regulate anterior and central zone compartmentation. PMID:24722417

Forces necessary for the disruption of the cisternal segments of cranial nerves II through XII.

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Tubbs, R Shane; Wellons, John C; Blount, Jeffrey P; Salter, E George; Oakes, W Jerry

2007-04-01

Manipulation of the cisternal segment of cranial nerves is often performed by the neurosurgeon. To date, attempts at quantifying the forces necessary to disrupt these nerves in situ, to our knowledge, has not been performed. The present study seeks to further elucidate the forces necessary to disrupt the cranial nerves while within the subarachnoid space. The cisternal segments of cranial nerves II through XII were exposed in six unfixed cadavers, all less than 6 hr postmortem. Forces to failure were then measured. Mean forces necessary to disrupt nerves for left sides in increasing order were found for cranial nerves IX, VII, IV, X, XII, III, VIII, XI, VI, V, and II, respectively. Mean forces for right-sided cranial nerves in increasing order were found for cranial nerves IX, VII, IV, X, XII, VIII, V, VI, XI, III, and II, respectively. Overall, cranial nerves requiring the least amount of force prior to failure included cranial nerves IV, VII, and IX. Those requiring the highest amount of force included cranial nerves II, V, VI, and XI. There was an approximately ten-fold difference between the least and greatest forces required to failure. Cranial nerve III was found to require significantly (P cranial nerves II through XII. We found that cranial nerve IX consistently took the least amount of force until its failure and cranial nerve II took the greatest. Other cranial nerves that took relatively small amount of force prior to failure included cranial nerves IV and VII. Although in vivo damage can occur prior to failure of a cranial nerve, our data may serve to provide a rough estimation for the maximal amount of tension that can be applied to a cranial nerve that is manipulated while within its cistern.

Assessment of tropism and effectiveness of new primate-derived hybrid recombinant AAV serotypes in the mouse and primate retina.

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Peter Charbel Issa

Full Text Available Adeno-associated viral vectors (AAV have been shown to be safe in the treatment of retinal degenerations in clinical trials. Thus, improving the efficiency of viral gene delivery has become increasingly important to increase the success of clinical trials. In this study, structural domains of different rAAV serotypes isolated from primate brain were combined to create novel hybrid recombinant AAV serotypes, rAAV2/rec2 and rAAV2/rec3. The efficacy of these novel serotypes were assessed in wild type mice and in two models of retinal degeneration (the Abca4(-/- mouse which is a model for Stargardt disease and in the Pde6b(rd1/rd1 mouse in vivo, in primate tissue ex-vivo, and in the human-derived SH-SY5Y cell line, using an identical AAV2 expression cassette. We show that these novel hybrid serotypes can transduce retinal tissue in mice and primates efficiently, although no more than AAV2/2 and rAAV2/5 serotypes. Transduction efficiency appeared lower in the Abca4(-/- mouse compared to wild type with all vectors tested, suggesting an effect of specific retinal diseases on the efficiency of gene delivery. Shuffling of AAV capsid domains may have clinical applications for patients who develop T-cell immune responses following AAV gene therapy, as specific peptide antigen sequences could be substituted using this technique prior to vector re-treatments.

Assessment of tropism and effectiveness of new primate-derived hybrid recombinant AAV serotypes in the mouse and primate retina.

Science.gov (United States)

Charbel Issa, Peter; De Silva, Samantha R; Lipinski, Daniel M; Singh, Mandeep S; Mouravlev, Alexandre; You, Qisheng; Barnard, Alun R; Hankins, Mark W; During, Matthew J; Maclaren, Robert E

2013-01-01

Adeno-associated viral vectors (AAV) have been shown to be safe in the treatment of retinal degenerations in clinical trials. Thus, improving the efficiency of viral gene delivery has become increasingly important to increase the success of clinical trials. In this study, structural domains of different rAAV serotypes isolated from primate brain were combined to create novel hybrid recombinant AAV serotypes, rAAV2/rec2 and rAAV2/rec3. The efficacy of these novel serotypes were assessed in wild type mice and in two models of retinal degeneration (the Abca4(-/-) mouse which is a model for Stargardt disease and in the Pde6b(rd1/rd1) mouse) in vivo, in primate tissue ex-vivo, and in the human-derived SH-SY5Y cell line, using an identical AAV2 expression cassette. We show that these novel hybrid serotypes can transduce retinal tissue in mice and primates efficiently, although no more than AAV2/2 and rAAV2/5 serotypes. Transduction efficiency appeared lower in the Abca4(-/-) mouse compared to wild type with all vectors tested, suggesting an effect of specific retinal diseases on the efficiency of gene delivery. Shuffling of AAV capsid domains may have clinical applications for patients who develop T-cell immune responses following AAV gene therapy, as specific peptide antigen sequences could be substituted using this technique prior to vector re-treatments.

Role of adenosine 5'-monophosphate-activated protein kinase in interleukin-6 release from isolated mouse skeletal muscle

DEFF Research Database (Denmark)

Glund, Stephan; Treebak, Jonas Thue; Long, Yun Chau

2009-01-01

IL-6 is released from skeletal muscle during exercise and has consequently been implicated to mediate beneficial effects on whole-body metabolism. Using 5-aminoimidazole-4-carboxamide-1-beta-4-ribofuranoside (AICAR), a pharmacological activator of 5'-AMP-activated protein kinase (AMPK), we tested......-type mice was also incubated with the AMPK activator A-769662. Incubation of mouse glycolytic extensor digitorum longus and oxidative soleus muscle for 2 h was associated with profound IL-6 mRNA production and protein release, which was suppressed by AICAR (P ... the hypothesis that AMPK modulates IL-6 release from isolated muscle. Skeletal muscle from AMPKalpha2 kinase-dead transgenic, AMPKalpha1 knockout (KO) and AMPKgamma3 KO mice and respective wild-type littermates was incubated in vitro, in the absence or presence of 2 mmol/liter AICAR. Skeletal muscle from wild...

Deformed Skull Morphology Is Caused by the Combined Effects of the Maldevelopment of Calvarias, Cranial Base and Brain in FGFR2-P253R Mice Mimicking Human Apert Syndrome.

Science.gov (United States)

Luo, Fengtao; Xie, Yangli; Xu, Wei; Huang, Junlan; Zhou, Siru; Wang, Zuqiang; Luo, Xiaoqing; Liu, Mi; Chen, Lin; Du, Xiaolan

2017-01-01

Apert syndrome (AS) is a common genetic syndrome in humans characterized with craniosynostosis. Apert patients and mouse models showed abnormalities in sutures, cranial base and brain, that may all be involved in the pathogenesis of skull malformation of Apert syndrome. To distinguish the differential roles of these components of head in the pathogenesis of the abnormal skull morphology of AS, we generated mouse strains specifically expressing mutant FGFR2 in chondrocytes, osteoblasts, and progenitor cells of central nervous system (CNS) by crossing Fgfr2 +/P253R-Neo mice with Col2a1-Cre, Osteocalcin-Cre (OC-Cre), and Nestin-Cre mice, respectively. We then quantitatively analyzed the skull and brain morphology of these mutant mice by micro-CT and micro-MRI using Euclidean distance matrix analysis (EDMA). Skulls of Col2a1-Fgfr2 +/P253R mice showed Apert syndrome-like dysmorphology, such as shortened skull dimensions along the rostrocaudal axis, shortened nasal bone, and evidently advanced ossification of cranial base synchondroses. The OC-Fgfr2 +/P253R mice showed malformation in face at 8-week stage. Nestin-Fgfr2 +/P253R mice exhibited increased dorsoventral height and rostrocaudal length on the caudal skull and brain at 8 weeks. Our study indicates that the abnormal skull morphology of AS is caused by the combined effects of the maldevelopment in calvarias, cranial base, and brain tissue. These findings further deepen our knowledge about the pathogenesis of the abnormal skull morphology of AS, and provide new clues for the further analyses of skull phenotypes and clinical management of AS.

Comparison of cranial form and function in association with diet in natricine snakes.

Science.gov (United States)

Hampton, Paul M

2011-12-01

The skull of squamates has many functions, with food acquisition and ingestion being paramount. Snakes vary interspecifically in the frequency, size, and types of prey that are consumed. Natural selection should favor phenotypes that minimize the costs of energy acquisition; therefore, trophic morphology should reflect a snake's primary prey type to enhance some aspect of feeding performance. I measured 19 cranial variables for six natricine species that vary in the frequency with which they consume frogs and fish. Both conventional and phylogenetically corrected analyses indicated that fish-eating snakes have relatively longer upper and lower jaw elements than frog-eating snakes, which tended to have broader skull components. I also compared the ratio of the in-lever to the out-lever lengths of the jaw-closing mechanism [jaw mechanical advantage (MA)] among species. Fish-eating snakes had significantly lower MAs in the jaws than did the frog-eating snakes. This result suggests that piscivores have faster closing jaws and that the jaws of frog-eating snakes have higher closing forces. Cranial morphology and the functional demands of prey capture and ingestion appear to be associated with primary prey type in natricine snakes. Copyright © 2011 Wiley-Liss, Inc.

The effect of the cranial bone CT numbers on the brain CT numbers

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Fukuda, Hitoshi; Kobayashi, Shotai; Koide, Hiromi; Yamaguchi, Shuhei; Okada, Kazunori; Shimote, Koichi; Tsunematsu, Tokugoro (Shimane Medical Univ., Izumo (Japan))

1989-06-01

The effects of the cranial size and the computed tomography (CT) numbers of the cranial bone on that of the brain were studied in 70 subjects, aged from 30 to 94 years. The subjects had no histories of cerebrovascular accidents and showed no abnormalities in the central nervous system upon physical examinations and a CT scan. We measured the average attenuation values (CT numbers) of each elliptical region (165 pixels, 0.39 cm{sup 2}) at the bilateral thalamus and at twelve areas of the deep white matter. Multiple regression analysis was used to assess the effects of age, cranial size, and cranial bone CT numbers on the brain CT numbers. The effect of the cranial bone CT numbers on the brain CT numbers was statistically significant. The brain CT numbers increased with the increase in the cranial bone CT numbers. There was, however, no significant correlation between brain CT numbers and cranial size. In measuring the brain CT numbers, it is desirable that consideration be given to the cranial bone CT numbers. (author).

Differentiation between probiotic and wild-type Bacillus cereus isolates by antibiotic susceptibility test and Fourier transform infrared spectroscopy (FT-IR).

Science.gov (United States)

Mietke, Henriette; Beer, W; Schleif, Julia; Schabert, G; Reissbrodt, R

2010-05-30

Animal feed often contains probiotic Bacillus strains used as feed additives. Spores of the non-pathogenic B. cereus var. toyoi (product name Toyocerin) are used. Distinguishing between toxic wild-type Bacillus cereus strains and this probiotic strain is essential for evaluating the quality and risk of feed. Bacillus cereus CIP 5832 (product name Paciflor was used as probiotic strain until 2001. The properties of the two probiotic strains are quite similar. Differentiating between probiotic strains and wild-type B. cereus strains is not easy. ss-lactam antibiotics such as penicillin and cefamandole exhibit an inhibition zone in the agar diffusion test of probiotic B. cereus strains which are not seen for wild-type strains. Therefore, performing the agar diffusion test first may make sense before FT-IR testing. When randomly checking these strains by Fourier transform infrared spectroscopy (FT-IR), the probiotic B. cereus strains were separated from wild-type B. cereus/B. thuringiensis/B. mycoides/B. weihenstephanensis strains by means of hierarchical cluster analysis. The discriminatory information was contained in the spectral windows 3000-2800 cm(-1) ("fatty acid region"), 1200-900 cm(-1) ("carbohydrate region") and 900-700 cm(-1) ("fingerprint region"). It is concluded that FT-IR spectroscopy can be used for the rapid quality control and risk analysis of animal feed containing probiotic B. cereus strains. (c) 2010 Elsevier B.V. All rights reserved.

Additive Manufacturing of Cranial Simulants for Blast Induced Traumatic Brain Injury

Science.gov (United States)

2017-08-28

REPORT TYPE 08/28/2017 Poster 4. TITLE AND SUBTITLE Additive Manufacturing of Cranial Sin1ulants for Blast Induced Traumatic Brain Injut’y 6... manufacturing techniques: Fused deposition modeling: ca sling molds Casting: white and gray matter Polymerization of injected solution...Sandia National Laboratories Conclusion MICHIGAN STAT[ l- I’ll I \\ I R <, I r \\ Additive manufacturrng provrdes a cost effective fabrration

Increased susceptibility to structural acute kidney injury in a mouse model of presymptomatic cardiomyopathy.

Science.gov (United States)

Pleasant, LaTawnya; Ma, Qing; Devarajan, Mahima; Parameswaran, Priyanka; Drake, Keri; Siroky, Brian; Shay-Winkler, Kritton; Robbins, Jeffrey; Devarajan, Prasad

2017-09-01

The early events that signal renal dysfunction in presymptomatic heart failure are unclear. We tested the hypothesis that functional and mechanistic changes occur in the kidney that precede the development of symptomatic heart failure. We employed a transgenic mouse model with cardiomyocyte-specific overexpression of mutant α-B-crystallin that develops slowly progressive cardiomyopathy. Presymptomatic transgenic mice displayed an increase in serum creatinine (1.17 ± 0.34 vs. wild type 0.65 ± 0.16 mg/dl, P kidneys exhibited a twofold upregulation of the Ren1 gene, marked overexpression of renin protein in the tubules, and a worsened response to ischemia-reperfusion injury based on serum creatinine (2.77 ± 0.66 in transgenic mice vs. 2.01 ± 0.58 mg/dl in wild type, P kidney that occur in early presymptomatic heart failure, which increase the susceptibility to subsequent acute kidney injury. Copyright © 2017 the American Physiological Society.

Mapping genetic variants for cranial vault shape in humans

DEFF Research Database (Denmark)

Roosenboom, Jasmien; Lee, Myoung Keun; Hecht, Jacqueline T

2018-01-01

The shape of the cranial vault, a region comprising interlocking flat bones surrounding the cerebral cortex, varies considerably in humans. Strongly influenced by brain size and shape, cranial vault morphology has both clinical and evolutionary relevance. However, little is known about the geneti...

Neurovascular compression syndrome of the eighth cranial nerve

International Nuclear Information System (INIS)

Itoh, Akinori

2010-01-01

Neurovascular compression syndrome (NVCS) involves neuropathy due to intracranial blood vessels compressing the cranial nerves. NVCS of the eighth cranial nerve is less reportedly established as a clinical entity than that of the fifth and seventh cranial nerves. We report 17 cases of NVCS of the eighth cranial nerve and their clinical features. Clinical symptoms and test findings among our subjects indicated that most were aged more than 65 years, were unilateral, had intermittent tinnitus, suffered attacks lasting a few seconds dozens of times a day, experienced dizziness concomitantly with tinnitus, aggravated tinnitus and dizziness when tilting the head toward the affected side and looking downward (positional tinnitus, positional dizziness), heard specific tinnitus sounds such as crackling differing from those in cochlear tinnitus, had mild or no hearing loss, were diagnosed with retrocochlear hearing disturbance due to an interpeak latency delay between waves I and III of the auditory brainstem response (ABR), often had no nystagmus or canal paresis (CP), were found in constructive interference steady state magnetic resonance imaging (CISS MRI) to have compression of the eighth cranial nerve by the vertebral artery (VA) or the anterior inferior cerebellar artery (AICA), rarely had concomitant facial spasms, and had tinnitus and dizziness markedly suppressed by carbamazepine. With the number of elderly individuals continuing to increase, cases of NVCS due to arteriosclerotic changes in cerebral blood vessels are expected to increase, making it necessary to consider NVCS in elderly subjects with dizziness, tinnitus, and hearing loss. (author)

Neurovascular compression syndrome of the eighth cranial nerve

Energy Technology Data Exchange (ETDEWEB)

Itoh, Akinori [Saitama Medical Univ., Faculty of Medicine, Moroyama, Saitama (Japan)

2010-04-15

Neurovascular compression syndrome (NVCS) involves neuropathy due to intracranial blood vessels compressing the cranial nerves. NVCS of the eighth cranial nerve is less reportedly established as a clinical entity than that of the fifth and seventh cranial nerves. We report 17 cases of NVCS of the eighth cranial nerve and their clinical features. Clinical symptoms and test findings among our subjects indicated that most were aged more than 65 years, were unilateral, had intermittent tinnitus, suffered attacks lasting a few seconds dozens of times a day, experienced dizziness concomitantly with tinnitus, aggravated tinnitus and dizziness when tilting the head toward the affected side and looking downward (positional tinnitus, positional dizziness), heard specific tinnitus sounds such as crackling differing from those in cochlear tinnitus, had mild or no hearing loss, were diagnosed with retrocochlear hearing disturbance due to an interpeak latency delay between waves I and III of the auditory brainstem response (ABR), often had no nystagmus or canal paresis (CP), were found in constructive interference steady state magnetic resonance imaging (CISS MRI) to have compression of the eighth cranial nerve by the vertebral artery (VA) or the anterior inferior cerebellar artery (AICA), rarely had concomitant facial spasms, and had tinnitus and dizziness markedly suppressed by carbamazepine. With the number of elderly individuals continuing to increase, cases of NVCS due to arteriosclerotic changes in cerebral blood vessels are expected to increase, making it necessary to consider NVCS in elderly subjects with dizziness, tinnitus, and hearing loss. (author)

Radiation-induced cranial nerve palsy and its causative factors in nasopharyngeal carcinoma

International Nuclear Information System (INIS)

Kong Lin; Zhang Youwang; Wu Yongru; Guo Xiaomao; Li Longgen

2005-01-01

Objective: To analyze the incidence and causative factors of radiation-induced cranial nerve palsy in patients with nasopharyngeal carcinoma (NPC). Methods: 512 NPC patients who underwent radiotherapy from January 1, 1989 to December 31, 1990 and from January 1, 1994 to December 31, 1995 were retrospectively analyzed. According to Fuzhou' 92 NPC Staging Classification, there are 31 patients in stage I, 212 in stage II, 198 in stage III and 71 in stage IV. All patients were treated by 60 Co or 6 MV X-ray with faciocervical fields or pre-auricular fields to primary area. Some patients were boosted by post-auricular fields or cranial fields. The median dose to the nasopharyngeal region was 7130 cGy by external beam radiotherapy. Thirty-four patients were boosted by brachytherapy. The medial dose to cervical lymph nodes was 6410 cGy as definitive treatment and 5480 cGy as prophylactic treatment. 101 patients were treated with combined chemotherapy. Results: The median follow-up was 6.7 years . Radiation-induced cranial nerve palsies occurred in 81 among the 512 patients. The 5- and 10-year cumulative incidences were 10.3%, 25.4%, respectively. The most common affected nerve was XII. On multivariates analysis, cranial nerve invasion before radiation, chemotherapy, dose to the nasopharyngeal region and age were the independent factors of radiation-induced cranial nerve palsy on nerve I-VII, while the N stage and the radiation fields were independent factors on nerve IX-XII. The cumulative incidence of cranial nerve I-VII palsies increased in patients with cranial nerve invasion, chemotherapy and the dose to the nasopharyngeal region (>7000 cGy). The cumulative incidence of cranial nerve IX- XII palsies increased in patients with advanced N stage. Patients in the first group of treatment field had the highest risk to progress cranial nerve IX-XII palsies, followed by the second group, and the third group had the lowest risk. Only 1 in 34 patients with brachytherapy

Genome Sequences of Three Vaccine Strains and Two Wild-Type Canine Distemper Virus Strains from a Recent Disease Outbreak in South Africa.

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Loots, Angelika K; Du Plessis, Morné; Dalton, Desiré Lee; Mitchell, Emily; Venter, Estelle H

2017-07-06

Canine distemper virus causes global multihost infectious disease. This report details complete genome sequences of three vaccine and two new wild-type strains. The wild-type strains belong to the South African lineage, and all three vaccine strains to the America 1 lineage. This constitutes the first genomic sequences of this virus from South Africa. Copyright © 2017 Loots et al.

Significcance of cranial nerve involvement shown by the prognosis of nasopharyngeal carcinoma

International Nuclear Information System (INIS)

Hui Zhouguang; Gao Li; Yi Junlin; Li Suyan; Jin Jing; Huang Xiaodong; Luo Jingwei; Xu Guozhen

2006-01-01

Objective: To analyze the cranial nerve involvement in nasophryngeal carcinoma and its relationship with the prognosis with the optimal treatment for such patients studied also. Methods: 935 untreated nasopharyngeal carcinoma patients, admitted into our hospital from January 1990 to June 1999, were analyzed retrospectively. These patients were divided into cranial nerve involved group and cranial nerve un- involved group by patients symptoms signs and/or images before the treatment. SPSS10.0 soft package was used to analyze the effect of cranial nerve involvement on the prognosis. Results: The overall percentage of cranial nerve involvement was 20.0%, of which the trigeminal nerve was most common . The 5-year local recurrence rate was 20.1% and 16.8% (P=0.465) in cranial nerve involved group and un-involved group, respectively. In the patients with cranial nerve involved, the 5-year local recurrence rates of patients who received boost skull base irradiation dose <70, 70-79 and ≥80 Gy was 38.1%, 24.5% and 16.0% (P =0.082), respectively. The 5-year distant metastasis rate was 31.6% and 19.5% (P=0.020) in cranial nerve involved group and un-involved group. The corresponding overall survival rates and disease-free survival rate was 62.2% and 78.1% (P=O.000) and 43.2%, 62.4% (P=0.000), respectively. By multivariate analysis, cranial nerve involvement was an independent factor both in overall survival (RR 1.62, P=0.001 ) and disease-free survival (RR=1.40, P=0.020). Conclusions: There are more distant metastasis, worse overall survival and disease-free survival in patients with cranial nerve involved. Boost irradiation to the involved skull base may improve the local control. Radiotherapy combined with chemotherapy for these patients may also have brighter future. (authors)

Anomalies in social behaviors and exploratory activities in an APPswe/PS1 mouse model of Alzheimer's disease.

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Filali, Mohammed; Lalonde, Robert; Rivest, Serge

2011-10-24

Alzheimer's disease is characterized by deficits in social communication, associated with generalized apathy or agitation, as well as social memory. To assess social behaviors in 6-month-old male APPswe/PS1 bigenics relative to non-transgenic controls, the 3-chamber test was used, together with open-field and elevated plus-maze tests of exploration. APPswe/PS1 mice were less willing to engage in social interaction than wild-type, avoiding an unfamiliar stimulus mouse, probably not due to generalized apathy because in both tests of exploratory activity the mutants were hyperactive. This study reveals reduced "sociability" combined with hyperactivity in an APPswe/PS1 mouse model of Alzheimer dementia. Copyright © 2011 Elsevier Inc. All rights reserved.

The evolution and development of cranial form in Homo sapiens

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Lieberman, Daniel E.; McBratney, Brandeis M.; Krovitz, Gail

2002-01-01

Despite much data, there is no unanimity over how to define Homo sapiens in the fossil record. Here, we examine cranial variation among Pleistocene and recent human fossils by using a model of cranial growth to identify unique derived features (autapomorphies) that reliably distinguish fossils attributed to “anatomically modern” H. sapiens (AMHS) from those attributed to various taxa of “archaic” Homo spp. (AH) and to test hypotheses about the changes in cranial development that underlie the ...

Characterization of two second-site mutations preventing wild type protein aggregation caused by a dominant negative PMA1 mutant.

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Pilar Eraso

Full Text Available The correct biogenesis and localization of Pma1 at the plasma membrane is essential for yeast growth. A subset of PMA1 mutations behave as dominant negative because they produce aberrantly folded proteins that form protein aggregates, which in turn provoke the aggregation of the wild type protein. One approach to understand this dominant negative effect is to identify second-site mutations able to suppress the dominant lethal phenotype caused by those mutant alleles. We isolated and characterized two intragenic second-site suppressors of the PMA1-D378T dominant negative mutation. We present here the analysis of these new mutations that are located along the amino-terminal half of the protein and include a missense mutation, L151F, and an in-frame 12bp deletion that eliminates four residues from Cys409 to Ala412. The results show that the suppressor mutations disrupt the interaction between the mutant and wild type enzymes, and this enables the wild type Pma1 to reach the plasma membrane.

Pontine extension of a tentorial schwannoma without cranial nerve involvement: a case report

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D'Urso Pietro

2011-12-01

Full Text Available Abstract Introduction Intracranial schwannomas unrelated to the cranial nerves are uncommon. We report a new case of tentorial schwannoma unrelated to the cranial nerves, with extension into the pons. A literature review with discussion of the most relevant pathogenetic aspects is also performed. Case presentation A 42-year-old Caucasian man was admitted with right-sided paresthesias and weakness of his upper and lower extremities. The neurological examination revealed right hemiparesis and hemi-hypoesthesia. A brain magnetic resonance imaging scan revealed a cerebellopontine lesion, arising from the left free edge of the tentorium, and extending into his pons. A piecemeal removal was performed through a retrosigmoid approach. The lesion was not found to be associated with any cranial nerves. The histological examination revealed a schwannoma Antoni type A. His postoperative course was uneventful. At one year follow-up, the patient was neurologically intact and the magnetic resonance imaging of his brain performed at that time showed complete removal without signs of recurrence. Conclusion Tentorial schwannomas are rare clinical entities. Knowledge of their clinical, radiological and anatomical characteristics is very important for the correct diagnosis and management.

Detection and differentiation of wild-type and vaccine strains of canine distemper virus by a duplex reverse transcription polymerase chain reaction.

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Dong, X Y; Li, W H; Zhu, J L; Liu, W J; Zhao, M Q; Luo, Y W; Chen, J D

2015-01-01

Canine distemper virus (CDV) is the cause of canine distemper (CD) which is a severe and highly contagious disease in dogs. In the present study, a duplex reverse transcription polymerase chain reaction (RT-PCR) method was developed for the detection and differentiation of wild-type and vaccine strains of CDV. Four primers were designed to detect and discriminate the two viruses by generating 638- and 781-bp cDNA products, respectively. Furthermore, the duplex RT-PCR method was used to detect 67 field samples suspected of CD from Guangdong province in China. Results showed that, 33 samples were to be wild-type-like. The duplex RT-PCR method exhibited high specificity and sensitivity which could be used to effectively detect and differentiate wild-type and vaccine CDV, indicating its use for clinical detection and epidemiological surveillance.

Comparative Study on Growth Performance of Transgenic (Over-Expressed OsNHX1 and Wild-Type Nipponbare under Different Salinity Regimes

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Nurul Kahrani ISHAK

2015-11-01

Full Text Available Transgenic Nipponbare which over-expressed a Na+/H+ antiporter gene OsNHX1 was used to compare its growth performance, water status and photosynthetic efficiency with its wild type under varying salinity regimes. Chlorophyll content, quantum yield and photosynthetic rate were measured to assess the impact of salinity stress on photosynthetic efficiency for transgenic and wild-type Nipponbare. Effects of salinity on water status and gas exchange to both lines were studied by measuring water use efficiency, instantaneous transpiration rate and stomatal conductance. Dry shoot weight and leaf area were determined after three months of growth to assess the impacts of salinity on the growth of those two lines. Our study showed that both lines were affected by salinity stress, however, the transgenic line showed higher photosynthetic efficiency, better utilization of water, and better growth due to low transpiration rate and stomatal conductance. Reduction of photosynthetic efficiency exhibited by the wild-type Nipponbare was correlated to its poor growth under salinity stress.

4D atlas of the mouse embryo for precise morphological staging.

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Wong, Michael D; van Eede, Matthijs C; Spring, Shoshana; Jevtic, Stefan; Boughner, Julia C; Lerch, Jason P; Henkelman, R Mark

2015-10-15

After more than a century of research, the mouse remains the gold-standard model system, for it recapitulates human development and disease and is quickly and highly tractable to genetic manipulations. Fundamental to the power and success of using a mouse model is the ability to stage embryonic mouse development accurately. Past staging systems were limited by the technologies of the day, such that only surface features, visible with a light microscope, could be recognized and used to define stages. With the advent of high-throughput 3D imaging tools that capture embryo morphology in microscopic detail, we now present the first 4D atlas staging system for mouse embryonic development using optical projection tomography and image registration methods. By tracking 3D trajectories of every anatomical point in the mouse embryo from E11.5 to E14.0, we established the first 4D atlas compiled from ex vivo 3D mouse embryo reference images. The resulting 4D atlas comprises 51 interpolated 3D images in this gestational range, resulting in a temporal resolution of 72 min. From this 4D atlas, any mouse embryo image can be subsequently compared and staged at the global, voxel and/or structural level. Assigning an embryonic stage to each point in anatomy allows for unprecedented quantitative analysis of developmental asynchrony among different anatomical structures in the same mouse embryo. This comprehensive developmental data set offers developmental biologists a new, powerful staging system that can identify and compare differences in developmental timing in wild-type embryos and shows promise for localizing deviations in mutant development. © 2015. Published by The Company of Biologists Ltd.

Idiopathic hypertrophic cranial pachymeningitis associated with Sweet's Syndrome

International Nuclear Information System (INIS)

Cano, Antonio; Ribes, Ramon; Riva, Andres de la; Rubio, Fernando Lopez; Sanchez, Carmen; Sancho, Jose L.

2002-01-01

A case of hypertrophic cranial pachymeningitis associated with Sweet's Syndrome is presented. Both entities have been described in association with several other chronic systemic inflammatory diseases and autoimmune conditions. To our knowledge the coexistence between Sweet's Syndrome and hypertrophic cranial pachymeningitis has not been reported up to date. We suggest a possible autoimmune or dysimmune mechanism in the pathogenesis of these two entities

Random genetic drift, natural selection, and noise in human cranial evolution.

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Roseman, Charles C

2016-08-01

This study assesses the extent to which relationships among groups complicate comparative studies of adaptation in recent human cranial variation and the extent to which departures from neutral additive models of evolution hinder the reconstruction of population relationships among groups using cranial morphology. Using a maximum likelihood evolutionary model fitting approach and a mixed population genomic and cranial data set, I evaluate the relative fits of several widely used models of human cranial evolution. Moreover, I compare the goodness of fit of models of cranial evolution constrained by genomic variation to test hypotheses about population specific departures from neutrality. Models from population genomics are much better fits to cranial variation than are traditional models from comparative human biology. There is not enough evolutionary information in the cranium to reconstruct much of recent human evolution but the influence of population history on cranial variation is strong enough to cause comparative studies of adaptation serious difficulties. Deviations from a model of random genetic drift along a tree-like population history show the importance of environmental effects, gene flow, and/or natural selection on human cranial variation. Moreover, there is a strong signal of the effect of natural selection or an environmental factor on a group of humans from Siberia. The evolution of the human cranium is complex and no one evolutionary process has prevailed at the expense of all others. A holistic unification of phenome, genome, and environmental context, gives us a strong point of purchase on these problems, which is unavailable to any one traditional approach alone. Am J Phys Anthropol 160:582-592, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Annotating and quantifying pri-miRNA transcripts using RNA-Seq data of wild type and serrate-1 globular stage embryos of Arabidopsis thaliana

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Daniel Lepe-Soltero

2017-12-01

Full Text Available The genome annotation for the model plant Arabidopsis thaliana does not include the primary transcripts from which MIRNAs are processed. Here we present and analyze the raw mRNA sequencing data from wild type and serrate-1 globular stage embryos of A. thaliana, ecotype Columbia. Because SERRATE is required for pri-miRNA processing, these precursors accumulate in serrate-1 mutants, facilitating their detection using standard RNA-Seq protocols. We first use the mapping of the RNA-Seq reads to the reference genome to annotate the potential primary transcripts of MIRNAs expressed in the embryo. We then quantify these pri-miRNAs in wild type and serrate-1 mutants. Finally, we use differential expression analysis to determine which are up-regulated in serrate-1 compared to wild type, to select the best candidates for bona fide pri-miRNAs expressed in the globular stage embryos. In addition, we analyze a previously published RNA-Seq dataset of wild type and dicer-like 1 mutant embryos at the globular stage [1]. Our data are interpreted and discussed in a separate article [2].

Annotating and quantifying pri-miRNA transcripts using RNA-Seq data of wild type and serrate-1 globular stage embryos of Arabidopsis thaliana.

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Lepe-Soltero, Daniel; Armenta-Medina, Alma; Xiang, Daoquan; Datla, Raju; Gillmor, C Stewart; Abreu-Goodger, Cei

2017-12-01

The genome annotation for the model plant Arabidopsis thaliana does not include the primary transcripts from which MIRNAs are processed. Here we present and analyze the raw mRNA sequencing data from wild type and serrate-1 globular stage embryos of A. thaliana , ecotype Columbia. Because SERRATE is required for pri-miRNA processing, these precursors accumulate in serrate-1 mutants, facilitating their detection using standard RNA-Seq protocols. We first use the mapping of the RNA-Seq reads to the reference genome to annotate the potential primary transcripts of MIRNAs expressed in the embryo. We then quantify these pri-miRNAs in wild type and serrate-1 mutants. Finally, we use differential expression analysis to determine which are up-regulated in serrate-1 compared to wild type, to select the best candidates for bona fide pri-miRNAs expressed in the globular stage embryos. In addition, we analyze a previously published RNA-Seq dataset of wild type and dicer-like 1 mutant embryos at the globular stage [1]. Our data are interpreted and discussed in a separate article [2].

Genotype-temperature interaction in the regulation of development, growth, and morphometrics in wild-type, and growth-hormone transgenic coho salmon.

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Mare Lõhmus

2010-04-01

Full Text Available The neuroendocrine system is an important modulator of phenotype, directing cellular genetic responses to external cues such as temperature. Behavioural and physiological processes in poikilothermic organisms (e.g. most fishes, are particularly influenced by surrounding temperatures.By comparing the development and growth of two genotypes of coho salmon (wild-type and transgenic with greatly enhanced growth hormone production at six different temperatures, ranging between 8 degrees and 18 degrees C, we observed a genotype-temperature interaction and possible trend in directed neuroendocrine selection. Differences in growth patterns of the two genotypes were compared by using mathematical models, and morphometric analyses of juvenile salmon were performed to detect differences in body shape. The maximum hatching and alevin survival rates of both genotypes occurred at 12 degrees C. At lower temperatures, eggs containing embryos with enhanced GH production hatched after a shorter incubation period than wild-type eggs, but this difference was not apparent at and above 16 degrees C. GH transgenesis led to lower body weights at the time when the yolk sack was completely absorbed compared to the wild genotype. The growth of juvenile GH-enhanced salmon was to a greater extent stimulated by higher temperatures than the growth of the wild-type. Increased GH production significantly influenced the shape of the salmon growth curves.Growth hormone overexpression by transgenesis is able to stimulate the growth of coho salmon over a wide range of temperatures. Temperature was found to affect growth rate, survival, and body morphology between GH transgenic and wild genotype coho salmon, and differential responses to temperature observed between the genotypes suggests they would experience different selective forces should they ever enter natural ecosystems. Thus, GH transgenic fish would be expected to differentially respond and adapt to shifts in environmental

Differential Expression of Claudin Family Proteins in Mouse Ovarian Serous Papillary Epithelial Adenoma in Aging FSH Receptor-Deficient Mutants

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Jayaprakash Aravindakshan

2006-12-01

Full Text Available Ovarian cancer is a deadly disease with long latency. To understand the consequences of loss of folliclestimulating hormone receptor (FSH-R signaling and to explore why the atrophic and anovulatory ovaries of follitropin receptor knockout (FORKO mice develop different types of ovarian tumors, including serous papillary epithelial adenoma later in life, we used mRNA expression profiling to gain a comprehensive view of misregulated genes. Using real-time quantitative reverse transcription-polymerase chain reaction, protein analysis, and cellular localization, we show, for the first time, in vivo evidence that, in the absence of FSH-R signaling, claudin-3, claudin-4, and claudin-11 are selectively upregulated, whereas claudin-1 decreases in ovarian surface epithelium and tumors in comparison to wild type. In vitro experiments using a mouse ovarian surface epithelial cell line derived from wild-type females reveal direct hormonal influence on claudin proteins. Although recent studies suggest that cell junction proteins are differentially expressed in ovarian tumors in women, the etiology of such changes remains unclear. Our results suggest an altered hormonal environment resulting from FSH-R loss as a cause of early changes in tight junction proteins that predispose the ovary to late-onset tumors that occur with aging. More importantly, this study identifies claudin-11 overexpression in mouse ovarian serous cystadenoma.

Ocular cranial nerve palsies secondary to sphenoid sinusitis

Institute of Scientific and Technical Information of China (English)

Aiman El Mograbi; Ethan Soudry

2017-01-01

Objective:The clinical presentation of sphenoid sinusitis can be highly variable.Rarely,sphenoid sinusitis may present with cranial nerve complications due to the proximity of these structures to the sphenoid sinus.Method:A case series from Rabin Medical Center and all cases of cranial nerves palsies secondary to sphenoid sinusitis that have been reported in the literature were reviewed.Results:Seventeen patients were identified.The abducent nerve was the most common cranial nerve affected (76％),followed by the oculomotor nerve (18％).One patient had combined oculomotor,trochlear and abducent palsies.The most common pathology was isolated purulent sphenoid sinusitis in 64％ followed by allergic fungal sinusitis (AFS) in 18％,and fungal infection in 18％.94％ had an acute presentation.The majority (85％) received a combined intravenous antibiotics and surgical treatment.The remainder received conservative treatment alone.Complete recovery of cranial nerve palsy was noted in 82％ during follow up.Conclusion:Sphenoid sinusitis presenting as diplopia and headaches is rare.A neoplastic process must be ruled out and early surgical intervention with intravenous antimicrobial therapy carry an excellent outcome with complete resolution of symptoms.

Roentgen stereophotogrammetry for analysis of cranial growth

International Nuclear Information System (INIS)

Selvik, G.; Alberius, P.; Fahlman, M.

1986-01-01

A system of roentgen stereophotogrammetric analysis (RSA) has been developed and its value in studies of cranial growth in both man and the experimental animal (rabbit) has been delineated. This method is based on measurements from metal bone marker images on roentgenograms. Two roentgen tubes simultaneously expose the object, which is placed in one of two types of calibration cages. The object position does not need to be identical from one examination to the next. The cage, holding indicators of predetermined internal positions (in two or four planes), defines a laboratory coordinate system. Two-dimensional image coordinates are obtained by means of a highly accurate cartographic instrument. By computer reconstruction of the x-ray beams through the markers, 3-D object coordinates are calculated. For subsequent analysis of growth processes, extensive software is necessary. To control intrasegmental stability (routinely performed at each examination), a minimum of two markers is required, whereas three markers are needed in each skeletal segment for kinematic analysis using the rigid-body concept. Careful planning of marker placement before implantation minimizes implant loss and instability that otherwise might be a problem. Complications other than bone marker loosening have been nonexistent. The technical accuracy is high. Consequently, roentgen stereophotogrammetry, with the aid of metallic implants, is a superior means to obtain biometric information on cranial growth with relative ease

Cranial pole nephrectomy in the pig model: anatomic analysis of arterial injuries in tridimensional endocasts.

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Pereira-Sampaio, Marco A; Henry, Robert W; Favorito, Luciano A; Sampaio, Francisco J B

2012-06-01

To assess the intrarenal arteries injuries after cranial pole nephrectomy in a pig model to compare these findings with those in humans. Polyester resin was injected through the ureter and the renal artery to make three-dimensional casts of 61 pig kidneys. The cranial pole of the kidneys was sectioned at four different sites before the solidification of the resin, and the casts were examined for arterial damage. Section performed through the hilus (15 kidneys): The cranial division of the renal artery was sectioned in two (13.33%) cases, the ventral branch of the cranial division of the renal artery was sectioned in 13 (86.7%) cases, and the dorsal branch of the cranial division of the renal artery was sectioned in 11 (73.34%) cases. Section at 0.5 cm cranial to the hilus (16 kidneys): The cranial division of the renal artery was sectioned in 1 (6.25%) case, the ventral branch of the cranial division of the renal artery was sectioned in 14 (87.5%) cases, and the dorsal branch of the cranial division of the renal artery was sectioned in 13 (81.25%) cases. Section at 1.0 cm cranial to the hilus (15 kidneys): The ventral branch of the cranial division of the renal artery was sectioned in five (33.33%) cases, and the dorsal branch of the cranial division of the renal artery was injured in five (33.33%) cases. Section at 1.5 cm cranial to the hilus (15 kidneys): No lesions were found in the main arteries, only in the interlobular branches. As previously demonstrated in humans, sections at 1.0 cm or more cranially to the hilus in pigs also showed a significant decrease in damage to the major intrarenal arteries. Therefore, as regards arterial damage, the pig kidney is a useful model for partial nephrectomy in the cranial (upper) pole.

Sex-Specific Diurnal Immobility Induced by Forced Swim Test in Wild Type and Clock Gene Deficient Mice

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Ningyue Li

2015-03-01

Full Text Available Objective: The link between alterations in circadian rhythms and depression are well established, but the underlying mechanisms are far less elucidated. We investigated the circadian characteristics of immobility behavior in wild type (WT mice and mice with mutations in core Clock genes. Methods: All mice were tested with forced swim test (FST at 4 h intervals. Results: These experiments revealed significant diurnal rhythms associated with immobility behavior in both male and female WT mice with sex-different circadian properties. In addition, male mice showed significantly less immobility during the night phase in comparison to female mice. Female Per1Brdm1 mice also showed significant rhythmicity. However, the timing of rhythmicity was very different from that observed in female wild type mice. Male Per1Brdm1 mice showed a pattern of rhythmicity similar to that of wild type mice. Furthermore, female Per1Brdm1 mice showed higher duration of immobility in comparison to male Per1Brdm1 mice in both daytime and early night phases. Neither Per2Brdm1 nor ClockΔ19 mice showed significant rhythmicity, but both female Per2Brdm1 and ClockΔ19 mice had lower levels of immobility, compared to males. Conclusions: This study highlights the differences in the circadian characteristics of immobility induced by FST in WT, ClockΔ19, Per1, and Per2 deficient mice.

Cranial suture biology of the Aleutian Island inhabitants.

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Cray, James; Mooney, Mark P; Siegel, Michael I

2011-04-01

Research on cranial suture biology suggests there is biological and taxonomic information to be garnered from the heritable pattern of suture synostosis. Suture synostosis along with brain growth patterns, diet, and biomechanical forces influence phenotypic variability in cranial vault morphology. This study was designed to determine the pattern of ectocranial suture synostosis in skeletal populations from the Aleutian Islands. We address the hypothesis that ectocranial suture synostosis pattern will differ according to cranial vault shape. Ales Hrdlicka identified two phenotypes in remains excavated from the Aleutian Island. The Paleo-Aleutians, exhibiting a dolichocranic phenotype with little prognathism linked to artifacts distinguished from later inhabitants, Aleutians, who exhibited a brachycranic phenotype with a greater amount of prognathism. A total of 212 crania representing Paleo-Aleuts and Aleutian as defined by Hrdlicka were investigated for suture synostosis pattern following standard methodologies. Comparisons were performed using Guttmann analyses. Results revealed similar suture fusion patterns for the Paleo-Aleut and Aleutian, a strong anterior to posterior pattern of suture fusion for the lateral-anterior suture sites, and a pattern of early termination at the sagittal suture sites for the vault. These patterns were found to differ from that reported in the literature. Because these two populations with distinct cranial shapes exhibit similar patterns of suture synostosis it appears pattern is independent of cranial shape in these populations of Homo sapiens. These findings suggest that suture fusion patterns may be population dependent and that a standardized methodology, using suture fusion to determine age-at-death, may not be applicable to all populations. Copyright © 2011 Wiley-Liss, Inc.

Multilocus sequence typing of commensal and enteropathogenic Escherichia coli from domestic and wild lagomorphs in Italy

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Giorgia Dotto

2015-12-01

Full Text Available The aim of the study was to determine the multilocus sequence types of Escherichia coli from diseased farm rabbits and apparently healthy wild lagomorphs, and the genetic relatedness among them. Fifty-five enteropathogenic E. coli from reared rabbits and 32 from wild rabbits and hares were characterised by multilocus sequence typing (MLST according to the Michigan State University EcMLST scheme. Isolates were differentiated into 37 sequence types (STs, which were grouped into 8 clonal complexes (CCs. The most common ST was ST140 (CC31, followed by ST238 and ST119 (CC17. MLST analysis revealed 22 novel STs. Phylogenetic analyses showed a heterogeneous distribution of STs into 3 clusters of genetically related strains. The genetic relationship among STs of different origin and the detection of new, as well as previously described STs as human pathogens, indicate a widespread distribution and adaptability of particular lineages to different hosts. These findings highlight the need for further research to improve the knowledge about E. coli populations colonising the gut of lagomorphs and their zoonotic potential.

Maintenance erlotinib in advanced nonsmall cell lung cancer: cost-effectiveness in EGFR wild-type across Europe

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Walleser S

2012-09-01

Full Text Available Silke Walleser,1 Joshua Ray,2 Helge Bischoff,3 Alain Vergnenègre,4 Hubertus Rosery,5 Christos Chouaid,6 David Heigener,7 Javier de Castro Carpeño,8 Marcello Tiseo,9 Stefan Walzer21Health Economic Consultancy, Renens, Switzerland; 2F Hoffmann-La Roche Pharmaceuticals AG, Basel, Switzerland; 3Thoracic Hospital of Heidelberg, Heidelberg, Germany; 4Limoges University Hospital, Limoges, France; 5Assessment-in-Medicine GmbH, Loerrach, Germany; 6Hospital Saint Antoine, Paris, France; 7Hospital Grosshansdorf, Grosshansdorf, Germany; 8University Hospital La Paz, Madrid, Spain; 9University Hospital of Parma, Parma, ItalyBackground: First-line maintenance erlotinib in patients with locally advanced or metastatic nonsmall cell lung cancer (NSCLC has demonstrated significant overall survival and progression-free survival benefits compared with best supportive care plus placebo, irrespective of epidermal growth factor receptor (EGFR status (SATURN trial. The cost-effectiveness of first-line maintenance erlotinib in the overall SATURN population has been assessed and published recently, but analyses according to EGFR mutation status have not been performed yet, which was the rationale for assessing the cost-effectiveness of first-line maintenance erlotinib specifically in EGFR wild-type metastatic NSCLC.Methods: The incremental cost per life-year gained of first-line maintenance erlotinib compared with best supportive care in patients with EGFR wild-type stable metastatic NSCLC was assessed for five European countries (the United Kingdom, Germany, France, Spain, and Italy with an area-under-the-curve model consisting of three health states (progression-free survival, progressive disease, death. Log-logistic survival functions were fitted to Phase III patient-level data (SATURN to model progression-free survival and overall survival. The first-line maintenance erlotinib therapy cost (modeled for time to treatment cessation, medication cost in later lines, and

Proteomics of Arabidopsis Seed Germination : a Comparative Study of Wild-Type and Gibberellin-Deficient Seeds

NARCIS (Netherlands)

Gallardo, K.; Job, C.; Groot, S.P.C.; Puype, M.; Vandekerckhove, J.; Job, D.

2002-01-01

We examined the role of gibberellins (GAs) in germination of Arabidopsis seeds by a proteomic approach. For that purpose, we used two systems. The first system consisted of seeds of the GA-deficient ga1 mutant, and the second corresponded to wild-type seeds incubated in paclobutrazol, a specific GA

Effects of ACNU and cranial irradiation on the mouse immune system

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Yamanaka, Ryuya; Tanaka, Ryuichi; Yoshida, Seiichi; Mori, Hiroshi; Takeda, Norio; Satoh, Mitsuya [Niigata Univ. (Japan). Brain Research Inst.

1993-02-01

The effects of 1-(4-amino-2-methyl-5-pyrimidinyl)-methyl- 3-(2-chloroethyl)-3-nitrosourea (ACNU) and cranial irradiation on the immune system were studied in three groups of 90 mice: Group A, intraperitoneal injection of ACNU (30 mg/kg); Group B, single exposure of 10 Gy to the head; and Group C, intraperitoneal injection of ACNU (30 mg/kg) and single exposure of 10 Gy to the head. Peripheral white blood cell counts, spleen cell subsets, natural killer (NK) cell activity, lymphocyte blastogenesis, and production of interferon (IFN)-[gamma] were analyzed once a week for 6 weeks after treatment. In Group A, NK cell activity decreased between weeks 4-5, concanavalin A blastogenesis decreased during weeks 1-5, and the levels of L3T4 (CD4) and Lyt2 cells (CD8) and IFN-[gamma] production decreased during weeks 2-5. However, all tested parameters returned to the normal range at 6 weeks. In Group B, all parameters except for the L3T4 cell level and the IFN-[gamma] production decreased during week 1, and returned to the normal range thereafter. The concentration of L3T4 cells decreased during week 2 and between weeks 5-6. The IFN-[gamma] production increased during week 1, decreased during week 2, and returned to the normal range thereafter. In Group C, the suppressive effects were severe and continued for a longer period than in either Group A or B. Concanavalin A blastogenesis, L3T4 cell concentration, and IFN-[gamma] production were still suppressed after 6 weeks. Therefore, intensive radiochemotherapy for brain tumor may suppress the immunological function. (author).

Subdural enhancement on postoperative spinal MRI after resection of posterior cranial fossa tumours

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Warmuth-Metz, M.; Solymosi, L. [Abteilung fuer Neuroradiologie, Klinikum der Bayerischen Julius Maximilians Universitaet, Josef-Schneider-Strasse 11, 97080, Wuerzburg (Germany); Kuehl, J. [Paediatric Oncology, Klinikum der Bayerischen Julius Maximilians Universitaet, Josef-Schneider-Strasse 11, 97080, Wuerzburg (Germany); Krauss, J. [Paediatric Neurosurgery, Klinikum der Bayerischen Julius Maximilians Universitaet, Josef-Schneider-Strasse 11, 97080, Wuerzburg (Germany)

2004-03-01

In malignant brain tumours which may disseminate staging, usually by cranial and spinal MRI is necessary. If MRI is performed in the postoperative period pitfalls should be considered. Nonspecific subdural contrast enhancement on spinal staging MRI is rarely reported after resection of posterior fossa tumours, which may be mistaken for dissemination of malignancy. We investigated the frequency of spinal subdural enhancement after posterior cranial fossa neurosurgery in children. We reviewed 53 postoperative spinal MRI studies performed for staging of paediatric malignant brain tumours, mainly infratentorial primitive neuroectodermal tumours 2-40 days after surgery. There was contrast enhancement in the spinal subdural space in seven cases. This was not seen in any of eight patients who had been operated upon for a supratentorial tumour. After resection of 45 posterior cranial fossa tumours the frequency of subdural enhancement was 15.5%. MRI showing subdural enhancement was obtained up to 25 days postoperatively. No patient with subdural enhancement had cerebrospinal fluid (CSF) examinations positive for tumour cells or developed dissemination of disease in the CSF. Because the characteristic appearances of subdural contrast enhancement, appropriate interpretation is possible; diagnosis of neoplastic meningitis should rarely be impeded. Because of the striking similarity to that in patients with a low CSF-pressure syndrome and in view of the fact that only resection of tumours of the posterior cranial fossa, usually associated with obstructive hydrocephalus, was followed by this type of enhancement one might suggest that rapid changes in CSF pressure are implicated, rather the effects of blood introduced into the spinal canal at surgery. (orig.)

Subdural enhancement on postoperative spinal MRI after resection of posterior cranial fossa tumours

International Nuclear Information System (INIS)

Warmuth-Metz, M.; Solymosi, L.; Kuehl, J.; Krauss, J.

2004-01-01

In malignant brain tumours which may disseminate staging, usually by cranial and spinal MRI is necessary. If MRI is performed in the postoperative period pitfalls should be considered. Nonspecific subdural contrast enhancement on spinal staging MRI is rarely reported after resection of posterior fossa tumours, which may be mistaken for dissemination of malignancy. We investigated the frequency of spinal subdural enhancement after posterior cranial fossa neurosurgery in children. We reviewed 53 postoperative spinal MRI studies performed for staging of paediatric malignant brain tumours, mainly infratentorial primitive neuroectodermal tumours 2-40 days after surgery. There was contrast enhancement in the spinal subdural space in seven cases. This was not seen in any of eight patients who had been operated upon for a supratentorial tumour. After resection of 45 posterior cranial fossa tumours the frequency of subdural enhancement was 15.5%. MRI showing subdural enhancement was obtained up to 25 days postoperatively. No patient with subdural enhancement had cerebrospinal fluid (CSF) examinations positive for tumour cells or developed dissemination of disease in the CSF. Because the characteristic appearances of subdural contrast enhancement, appropriate interpretation is possible; diagnosis of neoplastic meningitis should rarely be impeded. Because of the striking similarity to that in patients with a low CSF-pressure syndrome and in view of the fact that only resection of tumours of the posterior cranial fossa, usually associated with obstructive hydrocephalus, was followed by this type of enhancement one might suggest that rapid changes in CSF pressure are implicated, rather the effects of blood introduced into the spinal canal at surgery. (orig.)

Neurosyphilis Involving Cranial Nerves in Brain Stem: 2 Case Reports

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Jang, Ji Hye [Dept. of Radiology, Kyung Hee University College of Medicine, Seoul (Korea, Republic of); Choi, Woo Suk; Kim, Eui Jong [Dept. of Radiology, Kyung Hee University Hospital, Seoul (Korea, Republic of); Yoon, Sung Sang; Heo, Sung Hyuk [Dept. of Neurology, Kyung Hee University Hospital, Seoul (Korea, Republic of)

2012-01-15

Neurosyphilis uncommonly presents with cranial neuropathies in acute syphilitic meningitis and meningovascular neurosyphilis. We now report two cases in which the meningeal form of neurosyphilis involved cranial nerves in the brain stem: the oculomotor and trigeminal nerve.

Neurosyphilis Involving Cranial Nerves in Brain Stem: 2 Case Reports

International Nuclear Information System (INIS)

Jang, Ji Hye; Choi, Woo Suk; Kim, Eui Jong; Yoon, Sung Sang; Heo, Sung Hyuk

2012-01-01

Neurosyphilis uncommonly presents with cranial neuropathies in acute syphilitic meningitis and meningovascular neurosyphilis. We now report two cases in which the meningeal form of neurosyphilis involved cranial nerves in the brain stem: the oculomotor and trigeminal nerve.

Modelling biological control with wild-type and genetically modified baculoviruses in the Helicoverpa armigera-cotton system

NARCIS (Netherlands)

Sun, X.; Werf, van der W.; Bianchi, F.J.J.A.; Hu, Z.; Vlak, J.M.

2006-01-01

A comprehensive model was developed to simulate virus epizootics in a stage structured insect population and analyse scenarios for the biological control of cotton bollworm (CBW), Helicoverpa armigera, in cotton, using wild-type or genetically modified baculoviruses. In simulations on dosage and

CD7 in acute myeloid leukemia: correlation with loss of wild-type CEBPA, consequence of epigenetic regulation

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Drexler Hans G

2010-04-01

Full Text Available Abstract Background CD7 is a negative prognostic marker in myeloid malignancies. In acute myeloid leukemia (AML, an inverse correlation exists between expression of wild-type CEBPA and CD7. Aim of this study was to find out whether C/EBPα is a negative regulator of CD7 and which other regulatory mechanisms might be involved. Results As already described for primary AML cells, the majority of AML cell lines tested were either C/EBPα+/CD7- or C/EBPα-/CD7+. However, the existence of isolated CD7+ cell lines expressing wild-type C/EBPα challenges the notion that C/EBPα acts as a unique repressor of CD7. Furthermore, ectopic expression of CEBPA did not reduce CD7 in CD7+ cells and knock-down of C/EBPα failed to induce CD7 in CD7- cells. In contrast, the DNA demethylating agent Aza-2'deoxycytidine triggered CD7 expression in CD7- AML and in T-cell lines suggesting epigenetic regulation of CD7. Bisulfite sequencing data confirmed that CpGs in the CD7 exon1 region are methylated in CD7- cell lines, and unmethylated in CD7+ cell lines. Conclusion We confirmed an inverse correlation between the expression of wild-type CEBPA and of CD7 in AML cells. Our results contradict the hypothesis that C/EBPα acts as repressor for CD7, and instead show that epigenetic mechanisms are responsible for CD7 regulation, in AML cells as well as in T-cells, the typical CD7 expressing cell type.

Spinal Accessory Motor Neurons in the Mouse: A Special Type of Branchial Motor Neuron?

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Watson, Charles; Tvrdik, Petr

2018-04-16

The spinal accessory nerve arises from motor neurons in the upper cervical spinal cord. The axons of these motor neurons exit dorsal to the ligamentum denticulatum and form the spinal accessory nerve. The nerve ascends in the spinal subarachnoid space to enter the posterior cranial fossa through the foramen magnum. The spinal accessory nerve then turns caudally to exit through the jugular foramen alongside the vagus and glossopharyngeal nerves, and then travels to supply the sternomastoid and trapezius muscles in the neck. The unusual course of the spinal accessory nerve has long prompted speculation that it is not a typical spinal motor nerve and that it might represent a caudal remnant of the branchial motor system. Our cell lineage tracing data, combined with images from public databases, show that the spinal accessory motor neurons in the mouse transiently express Phox2b, a transcription factor that is required for development of brain stem branchial motor nuclei. While this is strong prima facie evidence that the spinal accessory motor neurons should be classified as branchial motor, the evolutionary history of these motor neurons in anamniote vertebrates suggests that they may be considered to be an atypical branchial group that possesses both branchial and somatic characteristics. Anat Rec, 2018. © 2018 Wiley Periodicals, Inc. © 2018 Wiley Periodicals, Inc.

Expression of a truncated receptor protein tyrosine phosphatase kappa in the brain of an adult transgenic mouse

DEFF Research Database (Denmark)

Shen, P; Canoll, P D; Sap, J

1999-01-01

processes such as axonal growth and target recognition, as has been demonstrated for certain Drosophila RPTPs. The brain distribution of RPTP-kappa-expressing cells has not been determined, however. In a gene-trap mouse model with a beta-gal+neo (beta-geo) insertion in the endogenous RPTP-kappa gene......-6596]. Nevertheless, since the transgene's expression is driven by the endogenous RPTP-kappa promoter, distribution of the truncated RPTP-kappa/beta-geo fusion protein should reflect the regional and cellular expression of wild-type RPTP-kappa, and thus may identify sites where RPTP-kappa is important. Towards...... that goal, we have used this mouse model to map the distribution of the truncated RPTP-kappa/beta-geo fusion protein in the adult mouse brain using beta-galactosidase as a marker enzyme. Visualization of the beta-galactosidase activity revealed a non-random pattern of expression, and identified cells...

Partially dissecting the steady-state electron fluxes in Photosystem I in wild-type and pgr5 and ndh mutants of Arabidopsis

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Jiancun eKou

2015-09-01

Full Text Available Cyclic electron flux (CEF around Photosystem I (PS I is difficult to quantify. We obtained the linear electron flux (LEFO2 through both photosystems and the total electron flux through PS I (ETR1 in Arabidopsis in CO2-enriched air. DeltaFlux = ETR1 – LEFO2 is an upper estimate of CEF, which consists of two components, an antimycin A-sensitive, PGR5 (proton gradient regulation 5 protein-dependent component and an insensitive component facilitated by a chloroplastic nicotinamide adenine dinucleotide dehydrogenase-like complex (NDH. Using wild type as well as pgr5 and ndh mutants, we observed that (1 40% of the absorbed light was partitioned to PS I; (2 at high irradiance a substantial antimycin A-sensitive CEF occurred in the wild type and the ndh mutant; (3 at low irradiance a sizable antimycin A-sensitive CEF occurred in the wild type but not in the ndh mutant, suggesting an enhancing effect of NDH in low light; and (4 in the pgr5 mutant, and the wild type and ndh mutant treated with antimycin A, a residual DeltaFlux existed at high irradiance, attributable to charge recombination and/or pseudo-cyclic electron flow. Therefore, in low-light-acclimated plants exposed to high light, DeltaFlux has contributions from various paths of electron flow through PS I.

Hepcidin regulation in wild-type and Hfe knockout mice in response to alcohol consumption: evidence for an alcohol-induced hypoxic response.

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Heritage, Mandy L; Murphy, Therese L; Bridle, Kim R; Anderson, Gregory J; Crawford, Darrell H G; Fletcher, Linda M

2009-08-01

Expression of Hamp1, the gene encoding the iron regulatory peptide hepcidin, is inappropriately low in HFE-associated hereditary hemochromatosis and Hfe knockout mice (Hfe(-/-)). Since chronic alcohol consumption is also associated with disturbances in iron metabolism, we investigated the effects of alcohol consumption on hepcidin mRNA expression in Hfe(-/-) mice. Hfe(-/-) and C57BL/6 (wild-type) mice were pair-fed either an alcohol liquid diet or control diet for up to 8 weeks. The mRNA levels of hepcidin and ferroportin were measured at the mRNA level by RT-PCR and protein expression of hypoxia inducible factor-1 alpha (HIF-1alpha) was measured by western blot. Hamp1 mRNA expression was significantly decreased and duodenal ferroportin expression was increased in alcohol-fed wild-type mice at 8 weeks. Time course experiments showed that the decrease in hepcidin mRNA was not immediate, but was significant by 4 weeks. Consistent with the genetic defect, Hamp1 mRNA was decreased and duodenal ferroportin mRNA expression was increased in Hfe(-/-) mice fed on the control diet compared with wild-type animals and alcohol further exacerbated these effects. HIF-1alpha protein levels were elevated in alcohol-fed wild-type animals compared with controls. Alcohol may decrease Hamp1 gene expression independently of the HFE pathway possibly via alcohol-induced hypoxia.

Electrophysiology of Extraocular Cranial Nerves: Oculomotor, Trochlear, and Abducens Nerve.

Science.gov (United States)

Hariharan, Praveen; Balzer, Jeffery R; Anetakis, Katherine; Crammond, Donald J; Thirumala, Parthasarathy D

2018-01-01

The utility of extraocular cranial nerve electrophysiologic recordings lies primarily in the operating room during skull base surgeries. Surgical manipulation during skull base surgeries poses a risk of injury to multiple cranial nerves, including those innervating extraocular muscles. Because tumors distort normal anatomic relationships, it becomes particularly challenging to identify cranial nerve structures. Studies have reported the benefits of using intraoperative spontaneous electromyographic recordings and compound muscle action potentials evoked by electrical stimulation in preventing postoperative neurologic deficits. Apart from surgical applications, electromyography of extraocular muscles has also been used to guide botulinum toxin injections in patients with strabismus and as an adjuvant diagnostic test in myasthenia gravis. In this article, we briefly review the rationale, current available techniques to monitor extraocular cranial nerves, technical difficulties, clinical and surgical applications, as well as future directions for research.

How Random Is Social Behaviour? Disentangling Social Complexity through the Study of a Wild House Mouse Population

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Perony, Nicolas; Tessone, Claudio J.; König, Barbara; Schweitzer, Frank

2012-01-01

Out of all the complex phenomena displayed in the behaviour of animal groups, many are thought to be emergent properties of rather simple decisions at the individual level. Some of these phenomena may also be explained by random processes only. Here we investigate to what extent the interaction dynamics of a population of wild house mice (Mus domesticus) in their natural environment can be explained by a simple stochastic model. We first introduce the notion of perceptual landscape, a novel tool used here to describe the utilisation of space by the mouse colony based on the sampling of individuals in discrete locations. We then implement the behavioural assumptions of the perceptual landscape in a multi-agent simulation to verify their accuracy in the reproduction of observed social patterns. We find that many high-level features – with the exception of territoriality – of our behavioural dataset can be accounted for at the population level through the use of this simplified representation. Our findings underline the potential importance of random factors in the apparent complexity of the mice's social structure. These results resonate in the general context of adaptive behaviour versus elementary environmental interactions. PMID:23209394

Ion permeabilities in mouse sperm reveal an external trigger for SLO3-dependent hyperpolarization.

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Julio C Chávez

Full Text Available Unlike most cells of the body which function in an ionic environment controlled within narrow limits, spermatozoa must function in a less controlled external environment. In order to better understand how sperm control their membrane potential in different ionic conditions, we measured mouse sperm membrane potentials under a variety of conditions and at different external K(+ concentrations, both before and after capacitation. Experiments were undertaken using both wild-type, and mutant mouse sperm from the knock-out strain of the sperm-specific, pH-sensitive, SLO3 K(+ channel. Membrane voltage data were fit to the Goldman-Hodgkin-Katz equation. Our study revealed a significant membrane permeability to both K(+ and Cl(- before capacitation, as well as Na(+. The permeability to both K(+ and Cl(- has the effect of preventing large changes in membrane potential when the extracellular concentration of either ion is changed. Such a mechanism may protect against undesired shifts in membrane potential in changing ionic environments. We found that a significant portion of resting membrane potassium permeability in wild-type sperm was contributed by SLO3 K(+ channels. We also found that further activation of SLO3 channels was the essential mechanism producing membrane hyperpolarization under two separate conditions, 1 elevation of external pH prior to capacitation and 2 capacitating conditions. Both conditions produced a significant membrane hyperpolarization in wild-type which was absent in SLO3 mutant sperm. Hyperpolarization in both conditions may result from activation of SLO3 channels by raising intracellular pH; however, demonstrating that SLO3-dependent hyperpolarization is achieved by an alkaline environment alone shows that SLO3 channel activation might occur independently of other events associated with capacitation. For example sperm may undergo stages of membrane hyperpolarization when reaching alkaline regions of the female genital tract

Lessons learned using different mouse models during space radiation-induced lung tumorigenesis experiments

Science.gov (United States)

Wang, Jian; Zhang, Xiangming; Wang, Ping; Wang, Xiang; Farris, Alton B.; Wang, Ya

2016-06-01

Unlike terrestrial ionizing radiation, space radiation, especially galactic cosmic rays (GCR), contains high energy charged (HZE) particles with high linear energy transfer (LET). Due to a lack of epidemiologic data for high-LET radiation exposure, it is highly uncertain how high the carcinogenesis risk is for astronauts following exposure to space radiation during space missions. Therefore, using mouse models is necessary to evaluate the risk of space radiation-induced tumorigenesis; however, which mouse model is better for these studies remains uncertain. Since lung tumorigenesis is the leading cause of cancer death among both men and women, and low-LET radiation exposure increases human lung carcinogenesis, evaluating space radiation-induced lung tumorigenesis is critical to enable safe Mars missions. Here, by comparing lung tumorigenesis obtained from different mouse strains, as well as miR-21 in lung tissue/tumors and serum, we believe that wild type mice with a low spontaneous tumorigenesis background are ideal for evaluating the risk of space radiation-induced lung tumorigenesis, and circulating miR-21 from such mice model might be used as a biomarker for predicting the risk.

Antibody Prevalence to Influenza Type A in Wild Boar of Northern Ukraine.

Science.gov (United States)

Kovalenko, Ganna; Molozhanova, Alona; Halka, Ihor; Nychyk, Serhiy

2017-12-01

A preliminary serological survey was carried out to assess the likelihood of influenza A (IA) infection in wild boar and begin to characterize the role of wild boar in the epidemiology of the IA virus (IAV). Sera collected from 120 wild boar that were hunted in 2014 were tested. To detect antibodies to IA, a blocking the enzyme-linked immunosorbent assay (ELISA) was used. Thirty boar were collected from each of four oblasts in the north central and northwestern regions of Ukraine. Antibodies against IAV were detected in 27 samples (22.5%; 95% confidence interval 16.0-30.8) and in at least some of the wild boar from all of the four oblasts. This preliminary survey of IA antibodies in wild boar populations of northern Ukraine indicates a substantial frequency of exposure to IAV throughout the region. Infection of wild boar populations could provide an alternative or additional route for spillover from wild populations to domestic animals and humans.

Taltirelin alleviates fatigue-like behavior in mouse models of cancer-related fatigue.

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Dougherty, John P; Wolff, Brian S; Cullen, Mary J; Saligan, Leorey N; Gershengorn, Marvin C

2017-10-01

Fatigue affects most cancer patients and has numerous potential causes, including cancer itself and cancer treatment. Cancer-related fatigue (CRF) is not relieved by rest, can decrease quality of life, and has no FDA-approved therapy. Thyrotropin-releasing hormone (TRH) has been proposed as a potential novel treatment for CRF, but its efficacy against CRF remains largely untested. Thus, we tested the TRH analog, taltirelin (TAL), in mouse models of CRF. To model fatigue, we used a mouse model of chemotherapy, a mouse model of radiation therapy, and mice bearing colon 26 carcinoma tumors. We used the treadmill fatigue test to assess fatigue-like behavior after treatment with TAL. Additionally, we used wild-type and TRH receptor knockout mice to determine which TRH receptor was necessary for the actions of TAL. Tumor-bearing mice displayed muscle wasting and all models caused fatigue-like behavior, with mice running a shorter distance in the treadmill fatigue test than controls. TAL reversed fatigue-like behavior in all three models and the mouse TRH 1 receptor was necessary for the effects of TAL. These data suggest that TAL may be useful in alleviating fatigue in all cancer patients and provide further support for evaluating TAL as a potential therapy for CRF in humans. Published by Elsevier Ltd.

A Single Amino Acid Difference between Mouse and Human 5-Lipoxygenase Activating Protein (FLAP) Explains the Speciation and Differential Pharmacology of Novel FLAP Inhibitors.

Science.gov (United States)

Blevitt, Jonathan M; Hack, Michael D; Herman, Krystal; Chang, Leon; Keith, John M; Mirzadegan, Tara; Rao, Navin L; Lebsack, Alec D; Milla, Marcos E

2016-06-10

5-Lipoxygenase activating protein (FLAP) plays a critical role in the metabolism of arachidonic acid to leukotriene A4, the precursor to the potent pro-inflammatory mediators leukotriene B4 and leukotriene C4 Studies with small molecule inhibitors of FLAP have led to the discovery of a drug binding pocket on the protein surface, and several pharmaceutical companies have developed compounds and performed clinical trials. Crystallographic studies and mutational analyses have contributed to a general understanding of compound binding modes. During our own efforts, we identified two unique chemical series. One series demonstrated strong inhibition of human FLAP but differential pharmacology across species and was completely inactive in assays with mouse or rat FLAP. The other series was active across rodent FLAP, as well as human and dog FLAP. Comparison of rodent and human FLAP amino acid sequences together with an analysis of a published crystal structure led to the identification of amino acid residue 24 in the floor of the putative binding pocket as a likely candidate for the observed speciation. On that basis, we tested compounds for binding to human G24A and mouse A24G FLAP mutant variants and compared the data to that generated for wild type human and mouse FLAP. These studies confirmed that a single amino acid mutation was sufficient to reverse the speciation observed in wild type FLAP. In addition, a PK/PD method was established in canines to enable preclinical profiling of mouse-inactive compounds. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Mutant INS-gene induced diabetes of youth: proinsulin cysteine residues impose dominant-negative inhibition on wild-type proinsulin transport.

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Ming Liu

2010-10-01

Full Text Available Recently, a syndrome of Mutant INS-gene-induced Diabetes of Youth (MIDY, derived from one of 26 distinct mutations has been identified as a cause of insulin-deficient diabetes, resulting from expression of a misfolded mutant proinsulin protein in the endoplasmic reticulum (ER of insulin-producing pancreatic beta cells. Genetic deletion of one, two, or even three alleles encoding insulin in mice does not necessarily lead to diabetes. Yet MIDY patients are INS-gene heterozygotes; inheritance of even one MIDY allele, causes diabetes. Although a favored explanation for the onset of diabetes is that insurmountable ER stress and ER stress response from the mutant proinsulin causes a net loss of beta cells, in this report we present three surprising and interlinked discoveries. First, in the presence of MIDY mutants, an increased fraction of wild-type proinsulin becomes recruited into nonnative disulfide-linked protein complexes. Second, regardless of whether MIDY mutations result in the loss, or creation, of an extra unpaired cysteine within proinsulin, Cys residues in the mutant protein are nevertheless essential in causing intracellular entrapment of co-expressed wild-type proinsulin, blocking insulin production. Third, while each of the MIDY mutants induces ER stress and ER stress response; ER stress and ER stress response alone appear insufficient to account for blockade of wild-type proinsulin. While there is general agreement that ultimately, as diabetes progresses, a significant loss of beta cell mass occurs, the early events described herein precede cell death and loss of beta cell mass. We conclude that the molecular pathogenesis of MIDY is initiated by perturbation of the disulfide-coupled folding pathway of wild-type proinsulin.

Evaluation of the Genetic and Nutritional Control of Obesity and Type 2 Diabetes in a Novel Mouse Model on Chromosome 7: An Insight into Insulin Signaling and Glucose Homeostasis

Energy Technology Data Exchange (ETDEWEB)

Nelson, S.; Dhar, M.

2003-01-01

Obesity is the main cause of type 2 diabetes, accounting for 90-95% of all diabetes cases in the US. Human obesity is a complex trait and can be studied using appropriate mouse models. A novel polygenic mouse model for studying the genetic and environmental contributions to and the physiological ramifications of obesity and related phenotypes is found in specific lines of mice bred and maintained at Oak Ridge National Laboratory. Heterozygous mice with a maternally inherited copy of two radiation-induced deletions in the p region of mouse chromosome 7, p23DFioD and p30PUb, have significantly greater body fat and show hyperinsulinemia compared to the wild-type. A single gene, Atp10c, maps to this critical region and codes for a putative aminophospholipid translocase. Biochemical and molecular studies were initiated to gain insight into obesity and glucose homeostasis in these animals and to study the biological role of Atp10c in creating these phenotypes. Glucose and insulin tolerance tests were standardized for the heterozygous p23DFioD and control mice on a custom-made diet containing 20% protein, 70% carbohydrate, and 10% fat (kcal). Atp10c expression profiles were also generated using Reverse-Transcriptase Polymerase Chain Reaction (RT-PCR). Heterozygous p23DFioD animals showed insulin resistance after receiving a dose of either 0.375 or 0.75 U/kg Illetin R insulin. RT-PCR data also shows differences in Atp10c expression in the mutants versus control mice. Using these standardized biochemical assays, future studies will further the understanding of genetic and nutritional controls of glucose homeostasis and obesity in animal models and subsequently in human populations.

Cranial shape variation in adult howler monkeys (Alouatta seniculus).

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Fiorenza, Luca; Bruner, Emiliano

2018-01-01

Howler monkeys (genus Alouatta) display a distinctive cranial architecture characterized by airorhynchy (or retroflexion of the facial skeleton on the cranial base), a small braincase, and a posteriorly oriented foramen magnum. This configuration has been associated with distinct factors including a high folivory diet, locomotion, and the presence of a specialized vocal tract characterized by large hyoid bone. However, the morphological relationships between the facial and neurocranial blocks in Alouatta have been scarcely investigated. In this study we quantitatively analyzed the cranial shape variation in Alouatta seniculus, to evaluate possible influences and constraints in face and braincase associated with airorhynchy. We also considered the structural role of the pteric area within the cranial functional matrix. We applied landmark-based analysis and multivariate statistics to 31 adult crania, computing shape analyses based on 3D coordinates registration as well as the analysis of the Euclidean distance matrix to investigate patterns of intraspecific morphological variability. Our results suggest that allometry is the main source of variation involved in shaping cranial morphology in howlers, influencing the degree of facial proportions and braincase flattening, and generating the main sexual differences. Larger individuals are characterized by a higher degree of airorhynchy, neurocranial flattening, and expansion of the zygomatic arch. Allometric variations influence the skull as a whole, without distinct patterns for face and braincase, which behave as an integrated morphological unit. A preliminary survey on the pteric pattern suggests that the morphology of this area may be the result of variations in the vertical growth rates between face and braincase. Future studies should be dedicated to the ontogenetic series and focus on airorhynchy in terms of differential growth among distinct cranial districts. © 2017 Wiley Periodicals, Inc.

Impairment of Hepcidin Upregulation by Lipopolysaccharide in the Interleukin-6 Knockout Mouse Brain

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Fa-Li Zhang

2017-11-01

Full Text Available To find out whether the Interleukin-6 (IL-6/signal transducer and activator of transcription 3 (STAT3 signaling pathway is involved in the expression of hepcidin in the mouse brain in vivo, we investigated the phosphorylation of STAT3, as well as the expression of hepcidin mRNA, ferroportin 1 (Fpn1 and ferritin light chain (Ft-L proteins in the cortex and hippocampus of LPS-treated wild type (IL-6+/+ and IL-6 knockout (IL-6-/- mice. We demonstrated that IL-6 knockout could significantly reduce the response of hepcidin mRNA, phospho-STAT3, Fpn1 and Ft-L protein expression to LPS treatment, in both the cortex and hippocampus of mice. Also, Stattic, an inhibitor of STAT3, significantly reduced the expression of phospho-STAT3 and hepcidin mRNA in the cortex and hippocampus of the LPS-treated wild type mice. These findings provide in vivo evidence for the involvement of the IL-6/STAT3 signaling pathway in the expression of hepcidin.

STUDY DATA OF KRAS- AND RAS-UNMUTATED (WILD TYPE OF COLORECTAL CANCER

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V. A. Gorbunova

2015-01-01

Full Text Available  Analysis of latest trials, comparing treatment schemes including chemotherapy with anti-EGFR monoclonal antibodies or bevacizumab is presented in this article. The data in these trials is inconsistent, but detailed analysis of FIRE-3 trial allows to distinguish a wild-type RAS patient group that benefits most from chemotherapy with cetuximab or panitumumab as 1st line metastatic colorectal cancer treatment. A final analysis of this patient group in CALGB/SWOG 80 405 trial is pending. The RAS analysis is pivotal for choice of 1st line chemotherapy.

Comparison of Ehrlichia muris strains isolated from wild mice and ticks and serologic survey of humans and animals with E. muris as antigen.

Science.gov (United States)

Kawahara, M; Ito, T; Suto, C; Shibata, S; Rikihisa, Y; Hata, K; Hirai, K

1999-04-01

In metropolitan Tokyo, the Ehrlichia muris seropositivity rate of 24 wild mice was 63% in Hinohara Village, but in the surrounding areas, it was 0 to 5%. This finding suggests that the reservoir of E. muris is focal. Among the 15 seropositive mice, ehrlichiae were isolated from 9 Apodemus speciosus mice and 1 A. argenteus mouse, respectively. Five ehrlichial isolates were obtained from 10 ticks (Haemaphysalis flava) collected in Asuke Town, Aichi Prefecture, where the E. muris type strain had been isolated. These new isolates were compared with the E. muris type strain. The mouse virulence and ultrastructure of the new isolates were similar to those of the type strain, and all of them were cross-reactive with each other, as well as with the type strain, by indirect immunofluorescent-antibody test. The levels of similarity of the base sequences of the 16S rRNA gene of one of the A. speciosus isolates and one of the tick isolates to that of the E. muris type strain were 99.79 and 99.93%, respectively. We suggest that all of these isolates are E. muris; that E. muris is not limited to Eothenomys kageus but infects other species of mice; and that E. muris is present at locations other than Aichi Prefecture. It appears that H. flava is a potential vector of E. muris. Twenty (1%) of 1803 humans from metropolitan Tokyo were found to be seropositive for E. muris antibodies. A serological survey revealed that exposure to E. muris or organisms antigenically cross-reactive to E. muris occurred among dogs, wild mice, monkeys, bears, deer, and wild boars in Gifu Prefecture, nearby prefectures, and Nagoya City, central Japan. However, human beings and Rattus norvegicus rats in this area were seronegative. These results indicate broader geographic distribution of and human and animal species exposure to E. muris or related Ehrlichia spp. in Japan.

Aetiology and pathogenesis of cranial cruciate ligament rupture in cats by histological examination.

Science.gov (United States)

Wessely, Marlis; Reese, Sven; Schnabl-Feichter, Eva

2017-06-01

Objectives The aim of this study was to examine histologically intact and ruptured cranial cruciate ligaments in cats, in order to evaluate whether degeneration is a prerequisite for rupture. Methods We performed a histological examination of 50 intact and 19 ruptured cranial cruciate ligaments in cadaver or client-owned cats, respectively, using light microscopy. Cats with stifle pathology were further divided into five age groups in order to investigate the relationship of changes in the ligament with lifespan. Cats with ruptured cranial cruciate ligaments were divided into two groups according to medical history (with presumed history of trauma or without any known history of trauma) in order to investigate the relationship of ligament rupture with a traumatic event. Data from 200 healthy cats were selected randomly and reviewed to make a statistical comparison of cats with and without cranial cruciate ligament rupture (reference group). Results On histological examination, the intact cranial cruciate ligaments showed basic parallel arrangement of the collagen fibres, with no relation to age. While cats of a more advanced age showed fibrocartilage in the middle of the cranial cruciate ligament - a likely physiological reaction to compression forces over the lifespan - degenerative changes within the fibrocartilage were absent in all cases, regardless of age or rupture status. Cats suffering from cranial cruciate ligament rupture without history of trauma were significantly older than cats in the reference group. Conclusions and relevance This study showed that differentiation of fibrocartilage in the middle of the cranial cruciate ligament is likely a physiological reaction to compressive forces and not a degenerative change associated with greater risk of rupture in advanced age. This finding in cats is distinct from the known decrease in differentiation of fibrocartilage in dogs with cranial cruciate ligament rupture. Furthermore, the histological examination

lambda. -prophage induction in repair-deficient and wild type E. coli strains by. gamma. -rays and heavy ions

Energy Technology Data Exchange (ETDEWEB)

Bonev, M.N.; Kozubek, S.; Krasavin, E.A.; Amirtajev, K.G. (Joint Inst. for Nuclear Research, Dubna (USSR))

1990-05-01

{lambda}-prophage induction in repair-deficient and wild-type E. coli strains by heavy ions and {gamma}-rays was investigated. The dose dependence of the fraction of induced cells has been measured and its initial slope ({lambda}-induction potency) determined. Induction by {gamma}-rays was found to be more efficient in a polA-repair-deficient strain; the value of {lambda}-induction potency is zero in lexA{sup -} and recA{sup -} strains. The {lambda}-induction potency potency increased with LET for wild-type cells but remained constant in polA{sup -} mutant cells. It is suggested that DNA damage triggering the {lambda}-prophage induction in the case of ionizing radiation could be a type of DNA single-strand break with complex structures which cannot be repaired by fast repair processes, and requires a substantial level of energy deposition for induction in a DNA molecule. (author).

Dinosaurs from the Maastrichtian-type area (southeastern Netherlands, northeastern Belgium)

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Jagt, J. W M; Mulder, E. W. A.; Schulp, Anne S.; Dortangs, Rudi W.; Fraaije, R. H B

In comparison to pre-1980 records of nonavian dinosaur remains from the Maastrichtian type strata, material collected during the past 20 years is both fairly common and diverse, consisting mostly of isolated cranial and post-cranial remains of hadrosaurids. With the exception of the type specimen of

Hepatocyte Hypoxia Inducible Factor-1 Mediates the Development of Liver Fibrosis in a Mouse Model of Nonalcoholic Fatty Liver Disease.

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Omar A Mesarwi

Full Text Available Obstructive sleep apnea (OSA is associated with the progression of non-alcoholic fatty liver disease (NAFLD to steatohepatitis and fibrosis. This progression correlates with the severity of OSA-associated hypoxia. In mice with diet induced obesity, hepatic steatosis leads to liver tissue hypoxia, which worsens with exposure to intermittent hypoxia. Emerging data has implicated hepatocyte cell signaling as an important factor in hepatic fibrogenesis. We hypothesized that hepatocyte specific knockout of the oxygen sensing α subunit of hypoxia inducible factor-1 (HIF-1, a master regulator of the global response to hypoxia, may be protective against the development of liver fibrosis.Wild-type mice and mice with hepatocyte-specific HIF-1α knockout (Hif1a-/-hep were fed a high trans-fat diet for six months, as a model of NAFLD. Hepatic fibrosis was evaluated by Sirius red stain and hydroxyproline assay. Liver enzymes, fasting insulin, and hepatic triglyceride content were also assessed. Hepatocytes were isolated from Hif1a-/-hep mice and wild-type controls and were exposed to sustained hypoxia (1% O2 or normoxia (16% O2 for 24 hours. The culture media was used to reconstitute type I collagen and the resulting matrices were examined for collagen cross-linking.Wild-type mice on a high trans-fat diet had 80% more hepatic collagen than Hif1a-/-hep mice (2.21 μg collagen/mg liver tissue, versus 1.23 μg collagen/mg liver tissue, p = 0.03, which was confirmed by Sirius red staining. Body weight, liver weight, mean hepatic triglyceride content, and fasting insulin were similar between groups. Culture media from wild-type mouse hepatocytes exposed to hypoxia allowed for avid collagen cross-linking, but very little cross-linking was seen when hepatocytes were exposed to normoxia, or when hepatocytes from Hif1a-/-hep mice were used in hypoxia or normoxia.Hepatocyte HIF-1 mediates an increase in liver fibrosis in a mouse model of NAFLD, perhaps due to liver

Acquired MET expression confers resistance to EGFR inhibition in a mouse model of glioblastoma multiforme.

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Jun, H J; Acquaviva, J; Chi, D; Lessard, J; Zhu, H; Woolfenden, S; Bronson, R T; Pfannl, R; White, F; Housman, D E; Iyer, L; Whittaker, C A; Boskovitz, A; Raval, A; Charest, A

2012-06-21

Glioblastoma multiforme (GBM) is an aggressive brain tumor for which there is no cure. Overexpression of wild-type epidermal growth factor receptor (EGFR) and loss of the tumor suppressor genes Ink4a/Arf and PTEN are salient features of this deadly cancer. Surprisingly, targeted inhibition of EGFR has been clinically disappointing, demonstrating an innate ability for GBM to develop resistance. Efforts at modeling GBM in mice using wild-type EGFR have proven unsuccessful to date, hampering endeavors at understanding molecular mechanisms of therapeutic resistance. Here, we describe a unique genetically engineered mouse model of EGFR-driven gliomagenesis that uses a somatic conditional overexpression and chronic activation of wild-type EGFR in cooperation with deletions in the Ink4a/Arf and PTEN genes in adult brains. Using this model, we establish that chronic activation of wild-type EGFR with a ligand is necessary for generating tumors with histopathological and molecular characteristics of GBMs. We show that these GBMs are resistant to EGFR kinase inhibition and we define this resistance molecularly. Inhibition of EGFR kinase activity using tyrosine kinase inhibitors in GBM tumor cells generates a cytostatic response characterized by a cell cycle arrest, which is accompanied by a substantial change in global gene expression levels. We demonstrate that an important component of this pattern is the transcriptional activation of the MET receptor tyrosine kinase and that pharmacological inhibition of MET overcomes the resistance to EGFR inhibition in these cells. These findings provide important new insights into mechanisms of resistance to EGFR inhibition and suggest that inhibition of multiple targets will be necessary to provide therapeutic benefit for GBM patients.

Altered Baseline and Nicotine-Mediated Behavioral and Cholinergic Profiles in ChAT-Cre Mouse Lines.

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Chen, Edison; Lallai, Valeria; Sherafat, Yasmine; Grimes, Nickolas P; Pushkin, Anna N; Fowler, J P; Fowler, Christie D

2018-02-28

The recent development of transgenic rodent lines expressing cre recombinase in a cell-specific manner, along with advances in engineered viral vectors, has permitted in-depth investigations into circuit function. However, emerging evidence has begun to suggest that genetic modifications may introduce unexpected caveats. In the current studies, we sought to extensively characterize male and female mice from both the ChAT (BAC) -Cre mouse line, created with the bacterial artificial chromosome (BAC) method, and ChAT (IRES) -Cre mouse line, generated with the internal ribosome entry site (IRES) method. ChAT (BAC) -Cre transgenic and wild-type mice did not differ in general locomotor behavior, anxiety measures, drug-induced cataplexy, nicotine-mediated hypolocomotion, or operant food training. However, ChAT (BAC) -Cre transgenic mice did exhibit significant deficits in intravenous nicotine self-administration, which paralleled an increase in vesicular acetylcholine transporter and choline acetyltransferase (ChAT) hippocampal expression. For the ChAT (IRES) -Cre line, transgenic mice exhibited deficits in baseline locomotor, nicotine-mediated hypolocomotion, and operant food training compared with wild-type and hemizygous littermates. No differences among ChAT (IRES) -Cre wild-type, hemizygous, and transgenic littermates were found in anxiety measures, drug-induced cataplexy, and nicotine self-administration. Given that increased cre expression was present in the ChAT (IRES) -Cre transgenic mice, as well as a decrease in ChAT expression in the hippocampus, altered neuronal function may underlie behavioral phenotypes. In contrast, ChAT (IRES) -Cre hemizygous mice were more similar to wild-type mice in both protein expression and the majority of behavioral assessments. As such, interpretation of data derived from ChAT-Cre rodents must consider potential limitations dependent on the line and/or genotype used in research investigations. SIGNIFICANCE STATEMENT Altered

Pathological Location of Cranial Nerves in Petroclival Lesions: How to Avoid Their Injury during Anterior Petrosal Approach.

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Borghei-Razavi, Hamid; Tomio, Ryosuke; Fereshtehnejad, Seyed-Mohammad; Shibao, Shunsuke; Schick, Uta; Toda, Masahiro; Yoshida, Kazunari; Kawase, Takeshi

2016-02-01

Objectives  Numerous surgical approaches have been developed to access the petroclival region. The Kawase approach, through the middle fossa, is a well-described option for addressing cranial base lesions of the petroclival region. Our aim was to gather data about the variation of cranial nerve locations in diverse petroclival pathologies and clarify the most common pathologic variations confirmed during the anterior petrosal approach. Method  A retrospective analysis was made of both videos and operative and histologic records of 40 petroclival tumors from January 2009 to September 2013 in which the Kawase approach was used. The anatomical variations of cranial nerves IV-VI related to the tumor were divided into several location categories: superior lateral (SL), inferior lateral (IL), superior medial (SM), inferior medial (IM), and encased (E). These data were then analyzed taking into consideration pathologic subgroups of meningioma, epidermoid, and schwannoma. Results  In 41% of meningiomas, the trigeminal nerve is encased by the tumor. In 38% of the meningiomas, the trigeminal nerve is in the SL part of the tumor, and it is in 20% of the IL portion of the tumor. In 38% of the meningiomas, the trochlear nerve is encased by the tumor. The abducens nerve is not always visible (35%). The pathologic nerve pattern differs from that of meningiomas for epidermoid and trigeminal schwannomas. Conclusion  The pattern of cranial nerves IV-VI is linked to the type of petroclival tumor. In a meningioma, tumor origin (cavernous, upper clival, tentorial, and petrous apex) is the most important predictor of the location of cranial nerves IV-VI. Classification of four subtypes of petroclival meningiomas using magnetic resonance imaging is very useful to predict the location of deviated cranial nerves IV-VI intraoperatively.

p38 mediates mechanical allodynia in a mouse model of type 2 diabetes

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Hong Yu

2010-05-01

Full Text Available Abstract Background Painful Diabetic Neuropathy (PDN affects more than 25% of patients with type 2 diabetes; however, the pathogenesis remains unclear due to lack of knowledge of the molecular mechanisms leading to PDN. In our current study, we use an animal model of type 2 diabetes in order to understand the roles of p38 in PDN. Previously, we have demonstrated that the C57BLK db/db (db/db mouse, a model of type 2 diabetes that carries the loss-of-function leptin receptor mutant, develops mechanical allodynia in the hind paws during the early stage (6-12 wk of age of diabetes. Using this timeline of PDN, we can investigate the signaling mechanisms underlying mechanical allodynia in the db/db mouse. Results We studied the role of p38 in lumbar dorsal root ganglia (LDRG during the development of mechanical allodynia in db/db mice. p38 phosphorylation was detected by immunoblots at the early stage of mechanical allodynia in LDRG of diabetic mice. Phosphorylated p38 (pp38 immunoreactivity was detected mostly in the small- to medium-sized LDRG neurons during the time period of mechanical allodynia. Treatment with an antibody against nerve growth factor (NGF significantly inhibited p38 phosphorylation in LDRG of diabetic mice. In addition, we detected higher levels of inflammatory mediators, including cyclooxygenase (COX 2, inducible nitric oxide synthases (iNOS, and tumor necrosis factor (TNF-α in LDRG neurons of db/db mice compared to non-diabetic db+ mice. Intrathecal delivery of SB203580, a p38 inhibitor, significantly inhibited the development of mechanical allodynia and the upregulation of COX2, iNOS and TNF-α. Conclusions Our findings suggest that NGF activated-p38 phosphorylation mediates mechanical allodynia in the db/db mouse by upregulation of multiple inflammatory mediators in LDRG.

Direct conversion of human pluripotent stem cells into cranial motor neurons using a piggyBac vector

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Riccardo De Santis

2018-05-01

Full Text Available Human pluripotent stem cells (PSCs are widely used for in vitro disease modeling. One of the challenges in the field is represented by the ability of converting human PSCs into specific disease-relevant cell types. The nervous system is composed of a wide variety of neuronal types with selective vulnerability in neurodegenerative diseases. This is particularly relevant for motor neuron diseases, in which different motor neurons populations show a different susceptibility to degeneration. Here we developed a fast and efficient method to convert human induced Pluripotent Stem Cells into cranial motor neurons of the branchiomotor and visceral motor subtype. These populations represent the motor neuron subgroup that is primarily affected by a severe form of amyotrophic lateral sclerosis with bulbar onset and worst prognosis. This goal was achieved by stable integration of an inducible vector, based on the piggyBac transposon, allowing controlled activation of Ngn2, Isl1 and Phox2a (NIP. The NIP module effectively produced electrophysiologically active cranial motor neurons. Our method can be easily extended to PSCs carrying disease-associated mutations, thus providing a useful tool to shed light on the cellular and molecular bases of selective motor neuron vulnerability in pathological conditions. Keywords: Spinal motor neuron, Cranial motor neuron, Induced pluripotent stem cells, Amyotrophic lateral sclerosis, Phox2a, piggyBac

Tissue- and Cell Type-Specific Expression of the Long Noncoding RNA Klhl14-AS in Mouse

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Sara Carmela Credendino

2017-01-01

Full Text Available lncRNAs are acquiring increasing relevance as regulators in a wide spectrum of biological processes. The extreme heterogeneity in the mechanisms of action of these molecules, however, makes them very difficult to study, especially regarding their molecular function. A novel lncRNA has been recently identified as the most enriched transcript in mouse developing thyroid. Due to its genomic localization antisense to the protein-encoding Klhl14 gene, we named it Klhl14-AS. In this paper, we highlight that mouse Klhl14-AS produces at least five splicing variants, some of which have not been previously described. Klhl14-AS is expressed with a peculiar pattern, characterized by diverse relative abundance of its isoforms in different mouse tissues. We examine the whole expression level of Klhl14-AS in a panel of adult mouse tissues, showing that it is expressed in the thyroid, lung, kidney, testis, ovary, brain, and spleen, although at different levels. In situ hybridization analysis reveals that, in the context of each organ, Klhl14-AS shows a cell type-specific expression. Interestingly, databases report a similar expression profile for human Klhl14-AS. Our observations suggest that this lncRNA could play cell type-specific roles in several organs and pave the way for functional characterization of this gene in appropriate biological contexts.

Vasculopathic Cranial Ocular Motor Neuropathy Following Sudden Emotional Stress

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Purvin, Valerie

2010-01-01

We describe three patients who experienced onset of a microvascular ocular motor nerve palsy in the setting of sudden emotional stress. Such emotional states are accompanied by a marked increase in sympathetic tone in some individuals. Mechanisms by which these autonomic changes might produce an ischemic cranial nerve palsy include intra-cranial vasoconstriction and transient systemic hypotension due to alterations in cardiac function.

[Rapidly progressive compromise of cranial pairs as neurosyphilis manifestation].

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Baccaro, Fernando; Moldes, Sofía; Novelli Poisson, Paola; Arduin, Julieta; Valerga, Mario

2012-01-01

Syphilis remains a common disease throughout the world, being neurosyphilis a relatively common manifestation. A case of a 34 years old male with HIV and neurosyphilis is presented, characterized by a clinical course evidenced by progressive palsy of cranial nerves. This case is unusual and a rare presentation of progressive cranial involvement with swallowing deficit, have found no similar data in the literature.

Effects of animal type (wild vs. domestic) and diet alfalfa level on intake and digestibility of European adult rabbits (Oryctolagus cuniculus)

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Pinheiro, Victor; Outor-Monteiro, D.; Mourão, J.L.; Cone, J.W.; Guimaraes Dias Lourenco, Ana

2018-01-01

The aim of this study was to evaluate the effect of the level of alfalfa in the diet on feed intake and digestibility of two types of rabbits, wild (Oryctolagus cuniculus algirus) vs. domestic (O. cuniculus cuniculus). Ten wild (W; mean LW = 927 g) and 10 domestic (D; mean LW = 4,645 g) adult rabbit

The In Vivo Granulopoietic Response to Dexamethasone Injection Is Abolished in Perforin-Deficient Mutant Mice and Corrected by Lymphocyte Transfer from Nonsensitized Wild-Type Donors

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Pedro Xavier-Elsas

2015-01-01

Full Text Available Exogenously administered glucocorticoids enhance eosinophil and neutrophil granulocyte production from murine bone-marrow. A hematological response dependent on endogenous glucocorticoids underlies bone-marrow eosinophilia induced by trauma or allergic sensitization/challenge. We detected a defect in granulopoiesis in nonsensitized, perforin-deficient mice. In steady-state conditions, perforin- (Pfp- deficient mice showed significantly decreased bone-marrow and blood eosinophil and neutrophil counts, and colony formation in response to GM-CSF, relative to wild-type controls of comparable age and/or weight. By contrast, peripheral blood or spleen total cell and lymphocyte numbers were not affected by perforin deficiency. Dexamethasone enhanced colony formation by GM-CSF-stimulated progenitors from wild-type controls, but not Pfp mice. Dexamethasone injection increased bone-marrow eosinophil and neutrophil counts in wild-type controls, but not Pfp mice. Because perforin is expressed in effector lymphocytes, we examined whether this defect would be corrected by transferring wild-type lymphocytes into perforin-deficient recipients. Short-term reconstitution of the response to dexamethasone was separately achieved for eosinophils and neutrophils by transfer of distinct populations of splenic lymphocytes from nonsensitized wild-type donors. Transfer of the same amount of splenic lymphocytes from perforin-deficient donors was ineffective. This demonstrates that the perforin-dependent, granulopoietic response to dexamethasone can be restored by transfer of innate lymphocyte subpopulations.

Mass Spectrometry Analysis of Wild-Type and Knock-in Q140/Q140 Huntington's Disease Mouse Brains Reveals Changes in Glycerophospholipids Including Alterations in Phosphatidic Acid and Lyso-Phosphatidic Acid.

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Vodicka, Petr; Mo, Shunyan; Tousley, Adelaide; Green, Karin M; Sapp, Ellen; Iuliano, Maria; Sadri-Vakili, Ghazaleh; Shaffer, Scott A; Aronin, Neil; DiFiglia, Marian; Kegel-Gleason, Kimberly B

2015-01-01

Huntington's disease (HD) is a neurodegenerative disease caused by a CAG expansion in the HD gene, which encodes the protein Huntingtin. Huntingtin associates with membranes and can interact directly with glycerophospholipids in membranes. We analyzed glycerophospholipid profiles from brains of 11 month old wild-type (WT) and Q140/Q140 HD knock-in mice to assess potential changes in glycerophospholipid metabolism. Polar lipids from cerebellum, cortex, and striatum were extracted and analyzed by liquid chromatography and negative ion electrospray tandem mass spectrometry analysis (LC-MS/MS). Gene products involved in polar lipid metabolism were studied using western blotting, immuno-electron microscopy and qPCR. Significant changes in numerous species of glycerophosphate (phosphatidic acid, PA) were found in striatum, cerebellum and cortex from Q140/Q140 HD mice compared to WT mice at 11 months. Changes in specific species could also be detected for other glycerophospholipids. Increases in species of lyso-PA (LPA) were measured in striatum of Q140/Q140 HD mice compared to WT. Protein levels for c-terminal binding protein 1 (CtBP1), a regulator of PA biosynthesis, were reduced in striatal synaptosomes from HD mice compared to wild-type at 6 and 12 months. Immunoreactivity for CtBP1 was detected on membranes of synaptic vesicles in striatal axon terminals in the globus pallidus. These novel results identify a potential site of molecular pathology caused by mutant Huntingtin that may impart early changes in HD.

A consensus definition of cataplexy in mouse models of narcolepsy.

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Scammell, Thomas E; Willie, Jon T; Guilleminault, Christian; Siegel, Jerome M

2009-01-01

People with narcolepsy often have episodes of cataplexy, brief periods of muscle weakness triggered by strong emotions. Many researchers are now studying mouse models of narcolepsy, but definitions of cataplexy-like behavior in mice differ across labs. To establish a common language, the International Working Group on Rodent Models of Narcolepsy reviewed the literature on cataplexy in people with narcolepsy and in dog and mouse models of narcolepsy and then developed a consensus definition of murine cataplexy. The group concluded that murine cataplexy is an abrupt episode of nuchal atonia lasting at least 10 seconds. In addition, theta activity dominates the EEG during the episode, and video recordings document immobility. To distinguish a cataplexy episode from REM sleep after a brief awakening, at least 40 seconds of wakefulness must precede the episode. Bouts of cataplexy fitting this definition are common in mice with disrupted orexin/hypocretin signaling, but these events almost never occur in wild type mice. It remains unclear whether murine cataplexy is triggered by strong emotions or whether mice remain conscious during the episodes as in people with narcolepsy. This working definition provides helpful insights into murine cataplexy and should allow objective and accurate comparisons of cataplexy in future studies using mouse models of narcolepsy.

Role of UV-inducible proteins in repair of various wild-type Escherichia coli cells

International Nuclear Information System (INIS)

Sedliakova, M.; Slezarikova, V.; Brozmanova, J.; Masek, F.; Bayerova, V.

1980-01-01

3 wild-type strains of E. coli, namely K12 AB2497, B/r WP2 and 15 555-7, proficient in excision and post-replication repair, differ markedly in their UV resistance. To elucidate this difference, the influence was investigated of induction by application of inducing fluence (IF) before lethal fluence (LF) on repair processes after LF. In cells distinguished by low UV resistance (E. coli 15 555-7; E. coli B/r WP2), dimer excision was less complete in cultures irradiated with IF + LF than in cultures irradiated with LF only. The highly resistant E. coli K12 AB2497 performed complete excision both after IF + LF or after LF alone. All 3 types of cell survived better after IF + LF than after LF only. Because, in most strains so far investigated, the application of IF reduced dimer excision and increased survival, dimer excision per se does not appear important for survival. We conclude that the rate and completeness of dimer excision can serve as a measure of efficiency of the excision system whose action is necessary for repair of another lesion. Cells of all investigated strains could not resume DNA replication and died progressively when irradiated with LF and post-incubated with chloramphenicol (LF CAP + ). Thus, it appears that inducible proteins are necessary for repair in all wild-type E. coli cells given with potentially lethal doses of UV irradiation. (orig.)

Stereotactic radiotherapy using Novalis for skull base metastases developing with cranial nerve symptoms.

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Mori, Yoshimasa; Hashizume, Chisa; Kobayashi, Tatsuya; Shibamoto, Yuta; Kosaki, Katsura; Nagai, Aiko

2010-06-01

Skull base metastases are challenging situations because they often involve critical structures such as cranial nerves. We evaluated the role of stereotactic radiotherapy (SRT) which can give high doses to the tumors sparing normal structures. We treated 11 cases of skull base metastases from other visceral carcinomas. They had neurological symptoms due to cranial nerve involvement including optic nerve (3 patients), oculomotor (3), trigeminal (6), abducens (1), facial (4), acoustic (1), and lower cranial nerves (1). The interval between the onset of cranial nerve symptoms and Novalis SRT was 1 week to 7 months. Eleven tumors of 8-112 ml in volume were treated by Novalis SRT with 30-50 Gy in 10-14 fractions. The tumors were covered by 90-95% isodose. Imaging and clinical follow-up has been obtained in all 11 patients for 5-36 months after SRT. Seven patients among 11 died from primary carcinoma or other visceral metastases 9-36 months after Novalis SRT. All 11 metastatic tumors were locally controlled until the end of the follow-up time or patient death, though retreatment for re-growth was done in 1 patient. In 10 of 11 patients, cranial nerve deficits were improved completely or partially. In some patients, the cranial nerve symptoms were relieved even during the period of fractionated SRT. Novalis SRT is thought to be safe and effective treatment for skull base metastases with involvement of cranial nerves and it may improve cranial nerve symptoms quickly.

Cranial radiotherapy predisposes to abdominal adiposity in survivors of childhood acute lymphocytic leukemia

International Nuclear Information System (INIS)

Siviero-Miachon, Adriana Aparecida; Spinola-Castro, Angela Maria; Lee, Maria Lúcia de Martino; Andreoni, Solange; Geloneze, Bruno; Lederman, Henrique; Guerra-Junior, Gil

2013-01-01

Advances in treatment of acute lymphocytic leukemia increased the likelihood of developing late treatment-associated effects, such as abdominal adiposity, increasing the risk of cardiovascular disease in this population. Cranial radiotherapy is one of the factors that might be involved in this process. The aim of this study was to determine the effect of cranial radiotherapy on adiposity indexes in survivors of acute lymphocytic leukemia. A comparative cross-sectional study of 56 acute lymphocytic leukemia survivors, chronological age between 15 and 24 years, assigned into two groups according to the exposure to cranial radiotherapy (25 irradiated and 31 non-irradiated), assessed according to body fat (dual energy X-ray absorptiometry), computed tomography scan-derived abdominal adipose tissue, lipid profile, and insulin resistance. Cranial radiotherapy increased body fat and abdominal adipose tissue and altered lipid panel. Yet, lipids showed no clinical relevance so far. There were significantly more obese patients among those who received cranial radiotherapy (52% irradiated versus 22.6% non-irradiated), based on dual energy X-ray absorptiometry body fat measurements. Nonetheless, no association was observed between cranial radiotherapy and body mass index, waist circumference, waist-to-height ratio or insulin resistance. Adolescent and young adult survivors of childhood acute lymphocytic leukemia showed an increase in body fat and an alteration of fat distribution, which were related to cranial radiotherapy. Fat compartment modifications possibly indicate a disease of adipose tissue, and cranial radiotherapy imports in this process

Efficient Reassignment of a Frequent Serine Codon in Wild-Type Escherichia coli.

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Ho, Joanne M; Reynolds, Noah M; Rivera, Keith; Connolly, Morgan; Guo, Li-Tao; Ling, Jiqiang; Pappin, Darryl J; Church, George M; Söll, Dieter

2016-02-19

Expansion of the genetic code through engineering the translation machinery has greatly increased the chemical repertoire of the proteome. This has been accomplished mainly by read-through of UAG or UGA stop codons by the noncanonical aminoacyl-tRNA of choice. While stop codon read-through involves competition with the translation release factors, sense codon reassignment entails competition with a large pool of endogenous tRNAs. We used an engineered pyrrolysyl-tRNA synthetase to incorporate 3-iodo-l-phenylalanine (3-I-Phe) at a number of different serine and leucine codons in wild-type Escherichia coli. Quantitative LC-MS/MS measurements of amino acid incorporation yields carried out in a selected reaction monitoring experiment revealed that the 3-I-Phe abundance at the Ser208AGU codon in superfolder GFP was 65 ± 17%. This method also allowed quantification of other amino acids (serine, 33 ± 17%; phenylalanine, 1 ± 1%; threonine, 1 ± 1%) that compete with 3-I-Phe at both the aminoacylation and decoding steps of translation for incorporation at the same codon position. Reassignments of different serine (AGU, AGC, UCG) and leucine (CUG) codons with the matching tRNA(Pyl) anticodon variants were met with varying success, and our findings provide a guideline for the choice of sense codons to be reassigned. Our results indicate that the 3-iodo-l-phenylalanyl-tRNA synthetase (IFRS)/tRNA(Pyl) pair can efficiently outcompete the cellular machinery to reassign select sense codons in wild-type E. coli.

Tissue distribution and developmental expression of type XVI collagen in the mouse.

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Lai, C H; Chu, M L

1996-04-01

The expression of a recently identified collagen, alpha 1 (XVI), in adult mouse tissue and developing mouse embryo was examined by immunohistochemistry and in situ hybridization. A polyclonal antiserum was raised against a recombinant fusion protein, which contained a segment of 161 amino acids in the N-terminal noncollagenous domain of the human alpha 1 (XVI) collagen. Immunoprecipitation of metabolically labelled human or mouse fibroblast cell lysates with this antibody revealed a major, bacterial collagenase sensitive polypeptide of approximately 210 kDa. The size agrees with the prediction from the full-length cDNA. Immunofluorescence examination of adult mouse tissues using the affinity purified antibody revealed a rather broad distribution of the protein. The heart, kidney, intestine, ovary, testis, eye, arterial walls and smooth muscles all exhibited significant levels of expression, while the skeletal muscle, lung and brain showed very restricted and low signals. During development, no significant expression of the mRNA or protein was observed in embryo of day 8 of gestation, but strong signals was detected in placental trophoblasts. Expression in embryos was detectable first after day 11 of gestation with weak positive signals appearing in the heart. In later stages of development, stronger RNA hybridizations were observed in a variety of tissues, particularly in atrial and ventricular walls of the developing heart, spinal root neural fibers and skin. These data demonstrate that type XVI collagen represents another collagenous component widely distributed in the extracellular matrix and may contribute to the structural integrity of various tissues.

Wnt signaling loss accelerates the appearance of neuropathological hallmarks of Alzheimer's disease in J20-APP transgenic and wild-type mice.

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Tapia-Rojas, Cheril; Inestrosa, Nibaldo C

2018-02-01

Alzheimer's disease (AD) is a neurodegenerative pathology characterized by aggregates of amyloid-β (Aβ) and phosphorylated tau protein, synaptic dysfunction, and spatial memory impairment. The Wnt signaling pathway has several key functions in the adult brain and has been associated with AD, mainly as a neuroprotective factor against Aβ toxicity and tau phosphorylation. However, dysfunction of Wnt/β-catenin signaling might also play a role in the onset and development of the disease. J20 APPswInd transgenic (Tg) mouse model of AD was treated i.p. with various Wnt signaling inhibitors for 10 weeks during pre-symptomatic stages. Then, cognitive, biochemical and histochemical analyses were performed. Wnt signaling inhibitors induced severe changes in the hippocampus, including alterations in Wnt pathway components and loss of Wnt signaling function, severe cognitive deficits, increased tau phosphorylation and Aβ 1-42 peptide levels, decreased Aβ42/Aβ40 ratio and Aβ 1-42 concentration in the cerebral spinal fluid, and high levels of soluble Aβ species and synaptotoxic oligomers in the hippocampus, together with changes in the amount and size of senile plaques. More important, we also observed severe alterations in treated wild-type (WT) mice, including behavioral impairment, tau phosphorylation, increased Aβ 1-42 in the hippocampus, decreased Aβ 1-42 in the cerebral spinal fluid, and hippocampal dysfunction. Wnt inhibition accelerated the development of the pathology in a Tg AD mouse model and contributed to the development of Alzheimer's-like changes in WT mice. These results indicate that Wnt signaling plays important roles in the structure and function of the adult hippocampus and suggest that inhibition of the Wnt signaling pathway is an important factor in the pathogenesis of AD. Read the Editorial Highlight for this article on page 356. © 2017 International Society for Neurochemistry.

Near-Infrared Spectroscopy, a Rapid Method for Predicting the Age of Male and Female Wild-Type and Wolbachia Infected Aedes aegypti.

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Maggy T Sikulu-Lord

2016-10-01

Full Text Available Estimating the age distribution of mosquito populations is crucial for assessing their capacity to transmit disease and for evaluating the efficacy of available vector control programs. This study reports on the capacity of the near-infrared spectroscopy (NIRS technique to rapidly predict the ages of the principal dengue and Zika vector, Aedes aegypti. The age of wild-type males and females, and males and females infected with wMel and wMelPop strains of Wolbachia pipientis were characterized using this method. Calibrations were developed using spectra collected from their heads and thoraces using partial least squares (PLS regression. A highly significant correlation was found between the true and predicted ages of mosquitoes. The coefficients of determination for wild-type females and males across all age groups were R2 = 0.84 and 0.78, respectively. The coefficients of determination for the age of wMel and wMelPop infected females were 0.71 and 0.80, respectively (P< 0.001 in both instances. The age of wild-type female Ae. aegypti could be identified as < or ≥ 8 days old with an accuracy of 91% (N = 501, whereas female Ae. aegypti infected with wMel and wMelPop were differentiated into the two age groups with an accuracy of 83% (N = 284 and 78% (N = 229, respectively. Our results also indicate NIRS can distinguish between young and old male wild-type, wMel and wMelPop infected Ae. aegypti with accuracies of 87% (N = 253, 83% (N = 277 and 78% (N = 234, respectively. We have demonstrated the potential of NIRS as a predictor of the age of female and male wild-type and Wolbachia infected Ae. aegypti mosquitoes under laboratory conditions. After field validation, the tool has the potential to offer a cheap and rapid alternative for surveillance of dengue and Zika vector control programs.

Brief communication: a cranial morphometric assessment of the taxonomic affinities of Trachypithecus auratus (E. Geoffroy, 1812 primates: Colobinae) with a reassessment of the T. auratus type specimen.

Science.gov (United States)

Ingicco, Thomas; Balzeau, Antoine; Callou, Cécile; Fitriana, Yuliana Sulistya

2011-10-01

The debate over the taxonomic position and affinities of Trachypithecus auratus has been ongoing since its identification by E. Geoffroy Saint-Hilaire in 1812. The type specimen of this species is housed in Muséum national d'Histoire naturelle in Paris (MNHN-ZM 2005-912). This point is debated due to the complex and fluctuating taxonomy of Southeast Asian Colobinae (Brandon-Jones et al.: Int J Primatol 25 (2004) 97-164) and to the fact that this individual is represented by a mounted skeleton. By means of 3D medical imaging methodologies we describe for the first time the cranial anatomy of the specimen MNHN-ZM 2005-912 and compare it with other Trachypithecus species, in order to test the molecular systematic hypotheses for affinities among the T. auratus-T. cristatus group. We ascertain the taxonomic attribution of this individual to the species Trachypithecus auratus species. The most diagnostic characters shared by the type specimen and Trachypithecus auratus compared to other species of Trachypithecus are the rounded orbits and the straight facial profile. We then try to clarify the inconsistencies concerning the geographical provenance of the type. The island of Java appears to be the most probable locality from a cluster analysis based on linear morphometry. After this approach and a discriminant analysis, a northeastern Javanese provenance of this specimen, as proposed by Brandon-Jones et al. (Int J Primatol 25 (2004) 97-164) is dubious. Finally we provide 3D models of the skull and the endocast, and a list of cranial landmark coordinates of the holotype for future research. Copyright © 2011 Wiley-Liss, Inc.

Isolated unilateral sixth cranial nerve palsy: A rare presentation of dengue fever

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Yang Liang Boo

2016-11-01

Full Text Available Dengue fever is a common mosquito-borne viral infection endemic in tropical and subtropical countries. Neurological manifestations in dengue infection are relatively uncommon, and include encephalitis, encephalopathy, neuromuscular disorders and neuro-ocular disorders. Cranial mononeuropathy is a rare manifestation of dengue infection. A 40-year-old man was diagnosed with isolated, unilateral sixth cranial nerve palsy complicating dengue infection. The patient was managed accordingly, and full ocular recovery was observed. This was the first reported case of isolated sixth cranial nerve palsy associated with dengue fever in Malaysia. It is important for clinicians to consider dengue as a differential diagnosis in patients presenting with fever and sixth cranial nerve palsy.

A mouse model of hereditary coproporphyria identified in an ENU mutagenesis screen

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Ashlee J. Conway

2017-08-01

Full Text Available A genome-wide ethyl-N-nitrosourea (ENU mutagenesis screen in mice was performed to identify novel regulators of erythropoiesis. Here, we describe a mouse line, RBC16, which harbours a dominantly inherited mutation in the Cpox gene, responsible for production of the haem biosynthesis enzyme, coproporphyrinogen III oxidase (CPOX. A premature stop codon in place of a tryptophan at amino acid 373 results in reduced mRNA expression and diminished protein levels, yielding a microcytic red blood cell phenotype in heterozygous mice. Urinary and faecal porphyrins in female RBC16 heterozygotes were significantly elevated compared with that of wild-type littermates, particularly coproporphyrinogen III, whereas males were biochemically normal. Attempts to induce acute porphyric crises were made using fasting and phenobarbital treatment on females. While fasting had no biochemical effect on RBC16 mice, phenobarbital caused significant elevation of faecal coproporphyrinogen III in heterozygous mice. This is the first known investigation of a mutagenesis mouse model with genetic and biochemical parallels to hereditary coproporphyria.

Cranial nerve injury after Le Fort I osteotomy.

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Kim, J-W; Chin, B-R; Park, H-S; Lee, S-H; Kwon, T-G

2011-03-01

A Le Fort I osteotomy is widely used to correct dentofacial deformity because it is a safe and reliable surgical method. Although rare, various complications have been reported in relation to pterygomaxillary separation. Cranial nerve damage is one of the serious complications that can occur after Le Fort I osteotomy. In this report, a 19-year-old man with unilateral cleft lip and palate underwent surgery to correct maxillary hypoplasia, asymmetry and mandibular prognathism. After the Le Fort I maxillary osteotomy, the patient showed multiple cranial nerve damage; an impairment of outward movement of the eye (abducens nerve), decreased vision (optic nerve), and paraesthesia of the frontal and upper cheek area (ophthalmic and maxillary nerve). The damage to the cranial nerve was related to an unexpected sphenoid bone fracture and subsequent trauma in the cavernous sinus during the pterygomaxillary osteotomy. Copyright © 2010 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

X-ray appearance of cranial lesions in hyperparathyroid osteodystuophy

International Nuclear Information System (INIS)

Spuzyak, M.M.; Tsarikovskaya, K.G.; Tkach, F.S.; David'yants, L.S.

1983-01-01

Craniographic data on 58 patients with hyperparathyroid osteodystrophy weere analyzed. Cranial changes revealed in 52 patients. Some data on the nature apd frequency of X-ray signs of cranial lesion in hyperparathyroid osteodystrophy are presented. The most frequent and typical X-ray signs of cranial lesions in hyperparathyroid osteodystrophy, are granular osteoporosis of the facial tectum and bones, the blurred contour of the internal tectum plate, foci of osteoclasia, osteoporosis of the elements of the Turkish saddle, resorption of the closing plates of the dental cavities, alterration of the thickness of the vault bones, symmetrical thinning, irregularity and obscurity of the external tectum plate, subperiosteal resorption of the cortical layer of the mandible (34.5%), partial resorption of the alveolar process of the jaw and epulis of the mandible

Unsteady 3D flow simulations in cranial arterial tree

Science.gov (United States)

Grinberg, Leopold; Anor, Tomer; Madsen, Joseph; Karniadakis, George

2008-11-01

High resolution unsteady 3D flow simulations in major cranial arteries have been performed. Two cases were considered: 1) a healthy volunteer with a complete Circle of Willis (CoW); and 2) a patient with hydrocephalus and an incomplete CoW. Computation was performed on 3344 processors of the new half petaflop supercomputer in TACC. Two new numerical approaches were developed and implemented: 1) a new two-level domain decomposition method, which couples continuous and discontinuous Galerkin discretization of the computational domain; and 2) a new type of outflow boundary conditions, which imposes, in an accurate and computationally efficient manner, clinically measured flow rates. In the first simulation, a geometric model of 65 cranial arteries was reconstructed. Our simulation reveals a high degree of asymmetry in the flow at the left and right parts of the CoW and the presence of swirling flow in most of the CoW arteries. In the second simulation, one of the main findings was a high pressure drop at the right anterior communicating artery (PCA). Due to the incompleteness of the CoW and the pressure drop at the PCA, the right internal carotid artery supplies blood to most regions of the brain.

Effects of social stress and intrauterine position on sexual phenotype in wild-type house mice (Mus musculus)

Science.gov (United States)

William J. Zielinski; John G. Vandenbergh; Monica M. Montano

1991-01-01

Wild-type house mice were used to test the effect of intrauterine position on anogenital distance (AGD) and to verify whether crowding stress would masculinize female pups, developing at all intrauterine positions, as has been demonstrated in CF-1 mice stressed by restraint, heat, and...

Vitamin K supplementation increases vitamin K tissue levels but fails to counteract ectopic calcification in a mouse model for pseudoxanthoma elasticum.

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Gorgels, Theo G M F; Waarsing, Jan H; Herfs, Marjolein; Versteeg, Daniëlle; Schoensiegel, Frank; Sato, Toshiro; Schlingemann, Reinier O; Ivandic, Boris; Vermeer, Cees; Schurgers, Leon J; Bergen, Arthur A B

2011-11-01

Pseudoxanthoma elasticum (PXE) is an autosomal recessive disorder in which calcification of connective tissue leads to pathology in skin, eye and blood vessels. PXE is caused by mutations in ABCC6. High expression of this transporter in the basolateral hepatocyte membrane suggests that it secretes an as-yet elusive factor into the circulation which prevents ectopic calcification. Utilizing our Abcc6 (-/-) mouse model for PXE, we tested the hypothesis that this factor is vitamin K (precursor) (Borst et al. 2008, Cell Cycle). For 3 months, Abcc6 (-/-) and wild-type mice were put on diets containing either the minimum dose of vitamin K required for normal blood coagulation or a dose that was 100 times higher. Vitamin K was supplied as menaquinone-7 (MK-7). Ectopic calcification was monitored in vivo by monthly micro-CT scans of the snout, as the PXE mouse model develops a characteristic connective tissue mineralization at the base of the whiskers. In addition, calcification of kidney arteries was measured by histology. Results show that supplemental MK-7 had no effect on ectopic calcification in Abcc6 ( -/- ) mice. MK-7 supplementation increased vitamin K levels (in skin, heart and brain) in wild-type and in Abcc6 (-/-) mice. Vitamin K tissue levels did not depend on Abcc6 genotype. In conclusion, dietary MK-7 supplementation increased vitamin K tissue levels in the PXE mouse model but failed to counteract ectopic calcification. Hence, we obtained no support for the hypothesis that Abcc6 transports vitamin K and that PXE can be cured by increasing tissue levels of vitamin K.

Cranial magnetic resonance imaging

International Nuclear Information System (INIS)

Elster, A.D.

1987-01-01

This illustrated work covers the diagnosis of central nervous system diseases by MRI. It focuses on strategies for detecting a wide range of intracranial disorders and includes protocols for cranial MRI. For each disease discussed, characteristic MR findings are described, and contrasted with CT and angiography where appropriate. Offers useful appendices on functional neuroanatomy and a glossary of terminology and abbreviations

Comparison of Ehrlichia muris Strains Isolated from Wild Mice and Ticks and Serologic Survey of Humans and Animals with E. muris as Antigen

OpenAIRE

Kawahara, Makoto; Ito, Tadahiko; Suto, Chiharu; Shibata, Shinichiro; Rikihisa, Yasuko; Hata, Kazuhisa; Hirai, Katsuya

1999-01-01

In metropolitan Tokyo, the Ehrlichia muris seropositivity rate of 24 wild mice was 63% in Hinohara Village, but in the surrounding areas, it was 0 to 5%. This finding suggests that the reservoir of E. muris is focal. Among the 15 seropositive mice, ehrlichiae were isolated from 9 Apodemus speciosus mice and 1 A. argenteus mouse, respectively. Five ehrlichial isolates were obtained from 10 ticks (Haemaphysalis flava) collected in Asuke Town, Aichi Prefecture, where the E. muris type strain had...

T-type voltage-gated calcium channels regulate the tone of mouse efferent arterioles

DEFF Research Database (Denmark)

Poulsen, Christian B; Al-Mashhadi, Rozh H; Cribbs, Leanne L

2011-01-01

Voltage-gated calcium channels are important for the regulation of renal blood flow and the glomerular filtration rate. Excitation-contraction coupling in afferent arterioles is known to require activation of these channels and we studied their role in the regulation of cortical efferent arteriolar...... tone. We used microdissected perfused mouse efferent arterioles and found a transient vasoconstriction in response to depolarization with potassium; an effect abolished by removal of extracellular calcium. The T-type voltage-gated calcium channel antagonists mibefradil and nickel blocked this potassium...... by immunocytochemistry to be located in mouse efferent arterioles, human pre- and postglomerular vasculature, and Ca(v)3.2 in rat glomerular arterioles. Inhibition of endothelial nitric oxide synthase by L-NAME or its deletion by gene knockout changed the potassium-elicited transient constriction to a sustained response...

Imaging assessment of isolated lesions affecting cranial nerve III

International Nuclear Information System (INIS)

Garcia, Marcelo de Mattos; Martins, Jose Carlos Tadeu

2005-01-01

The aim of this study is to review the anatomy and main pathologic conditions affecting cranial nerve III using imaging studies, particularly magnetic resonance imaging. Imaging methods are essential in the evaluation of patients with suspected lesions of the oculomotor nerve once signs and symptoms are unspecific and a large number of diseases can affect cranial nerve III. A brief review of the literature is also presented. (author)

Isovaleric acidaemia: cranial CT and MRI findings

International Nuclear Information System (INIS)

Sogut, Ayhan; Acun, Ceyda; Tomsac, Nazan; Demirel, Fatma; Aydin, Kubilay; Aktuglu, Cigdem

2004-01-01

Isovaleric acidaemia is an inborn error of leucine metabolism due to deficiency of isovaleryl-CoA dehydrogenase, which results in accumulation of isovaleric acid in body fluids. There are acute and chronic-intermittent forms of the disease. We present the cranial CT and MRI findings of a 19-month-old girl with the chronic-intermittent form of isovaleric acidaemia. She presented with severe metabolic acidosis, hyperglycaemia, glycosuria, ketonuria and acute encephalopathy. Cranial CT revealed bilateral hypodensity of the globi pallidi. MRI showed signal changes in the globi pallidi and corticospinal tracts of the mesencephalon, which were hypointense on T1-weighted and hyperintense on T2-weighted images. (orig.)

Isovaleric acidaemia: cranial CT and MRI findings

Energy Technology Data Exchange (ETDEWEB)

Sogut, Ayhan; Acun, Ceyda; Tomsac, Nazan; Demirel, Fatma [Department of Paediatrics, Karaelmas University, Zonguldak (Turkey); Aydin, Kubilay [Department of Radiology, Istanbul Medical School, Istanbul University, Camlikyolu, B. mehmetpasa sokak yavuz apt. No:10/10, Etiler, Istanbul (Turkey); Aktuglu, Cigdem [Department of Paediatrics, Cerrahpasa Medical School, Istanbul University, Istanbul (Turkey)

2004-02-01

Isovaleric acidaemia is an inborn error of leucine metabolism due to deficiency of isovaleryl-CoA dehydrogenase, which results in accumulation of isovaleric acid in body fluids. There are acute and chronic-intermittent forms of the disease. We present the cranial CT and MRI findings of a 19-month-old girl with the chronic-intermittent form of isovaleric acidaemia. She presented with severe metabolic acidosis, hyperglycaemia, glycosuria, ketonuria and acute encephalopathy. Cranial CT revealed bilateral hypodensity of the globi pallidi. MRI showed signal changes in the globi pallidi and corticospinal tracts of the mesencephalon, which were hypointense on T1-weighted and hyperintense on T2-weighted images. (orig.)

Acid-sensing ion channels (ASICs) in mouse skeletal muscle afferents are heteromers composed of ASIC1a, ASIC2, and ASIC3 subunits

Science.gov (United States)

Gautam, Mamta; Benson, Christopher J.

2013-01-01

Acid-sensing ion channels (ASICs) are expressed in skeletal muscle afferents, in which they sense extracellular acidosis and other metabolites released during ischemia and exercise. ASICs are formed as homotrimers or heterotrimers of several isoforms (ASIC1a, ASIC1b, ASIC2a, ASIC2b, and ASIC3), with each channel displaying distinct properties. To dissect the ASIC composition in muscle afferents, we used whole-cell patch-clamp recordings to study the properties of acid-evoked currents (amplitude, pH sensitivity, the kinetics of desensitization and recovery from desensitization, and pharmacological modulation) in isolated, labeled mouse muscle afferents from wild-type (C57BL/6J) and specific ASIC−/− mice. We found that ASIC-like currents in wild-type muscle afferents displayed fast desensitization, indicating that they are carried by heteromeric channels. Currents from ASIC1a−/− muscle afferents were less pH-sensitive and displayed faster recovery, currents from ASIC2−/− mice showed diminished potentiation by zinc, and currents from ASIC3−/− mice displayed slower desensitization than those from wild-type mice. Finally, ASIC-like currents were absent from triple-null mice lacking ASIC1a, ASIC2a, and ASIC3. We conclude that ASIC1a, ASIC2a, and ASIC3 heteromers are the principle channels in skeletal muscle afferents. These results will help us understand the role of ASICs in exercise physiology and provide a molecular target for potential drug therapies to treat muscle pain.—Gautam, M., Benson, C. J. Acid-sensing ion channels (ASICs) in mouse skeletal muscle afferents are heteromers composed of ASIC1a, ASIC2, and ASIC3 subunits. PMID:23109675

Neurologic disturbances in case of breast cancer disseminated into cranial bones

International Nuclear Information System (INIS)

Tarasyuk, S.V.; Letyagin, V.P.

1986-01-01

The paper presents data on 52 cases of breast cancer disseminated into cranial vault bones (2 into the orbit). Metastases into the brain (2) and meninges (6) were detected in 17 cases with the aid of computerized tomography of the brain and examination of cerebrospinal fluid. The latter cases were not included into the study group. Metastases into cranial bones were identified by craniography and scanning of the skeleton. Half the patients (18 out of 35) revealed the following neurologic syndromes which were determined by the site of metastases into cranial vault bones and tumour growth pattern (into cranial cavity or soft tissues of the head): lesions in ramus primus nervi trigemini, greater occipital nerve, migraine, pseudotumorous and pseudoencephalitic syndromes. Cases of such neurologic disorders require an all-round examination including ophthalmooscopy, EEG, computerized tomography of the brain, craniography and scanning of the skeleton

Cranial nerve palsies in Nigerian children

African Journals Online (AJOL)

PROF. EZECHUKWU

2014-01-08

Jan 8, 2014 ... Introduction. Cranial nerve palsy is a common clinical problem ... Methodology ... The two cases with three-nerve involvement were re- lated to viral encephalitis and cerebral contusion from ... RTA = road traffic accident.

Dexamethasone minimizes the risk of cranial nerve injury during CEA.

Science.gov (United States)

Regina, Guido; Angiletta, Domenico; Impedovo, Giovanni; De Robertis, Giovanni; Fiorella, Marialuisa; Carratu', Maria Rosaria

2009-01-01

The incidence of cranial and cervical nerve injury during carotid endarterectomy (CEA) ranges from less than 7.6% to more than 50%. Lesions are mainly due to surgical maneuvers such as traction, compression, tissue electrocoagulation, clamping, and extensive dissections. The use of dexamethasone (DEX) and its beneficial effects in spinal cord injuries have already been described. We investigated whether DEX could also be beneficial to minimize the incidence of cranial and cervical nerve injury during CEA. To evaluate whether dexamethasone is able to reduce the incidence of cranial nerve injuries. From March 1999 through April 2006, 1126 patients undergoing CEA because of high-grade carotid stenosis were enrolled and randomized by predetermined randomization tables into two groups. The first group, "A", included 586 patients that all received an intravenous administration of dexamethasone following a therapeutic scheme. The second group, "B", included 540 control subjects that received the standard pre- and postoperative therapy. All patients were submitted to a deep cervical plexus block, eversion carotid endarterectomy, and selective shunting. Three days after the operation, an independent neurologist and otorhinolaryngologist evaluated the presence of cranial nerve deficits. All patients (group A and group B) showing nerve injuries continued the treatment (8 mg of dexamethasone once in the morning) for 7 days and were re-evaluated after 2 weeks, 30 days, and every 3 months for 1 year. Recovery time took from 2 weeks to 12 months, with a mean time of 3.6 months. The chi(2) test was used to compare the two groups and to check for statistical significance. The incidence of cranial nerve dysfunction was higher in group B and the statistical analysis showed a significant effect of dexamethasone in preventing the neurological damage (P = .0081). The incidence of temporary lesions was lower in group A and the chi(2) test yielded a P value of .006. No statistically

Macrostructure of the Cranial Cervical Ganglion in the River Buffalo (Bubalus Bubalis

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Hossein Dehghani

2011-09-01

Full Text Available AbstractThe autonomic nervous system consists of a vast range of nerves and ganglions. Anatomical studies have demonstrated that the sympathetic innervations of the head and neck are affected by the neurons that ramify from the cranial cervical ganglion (CCG. The CCG is the end of the sympathetic cervical trunk, which runs with the vagal nerve during its cervical course. In this study sixteen adult (2 - 5 year river buffalo of both sexes (eight male, eight female weighing around 250 - 450 kg were dissected to investigate the weight, situation and arrangement of nerve branches of the cranial cervical ganglion bilaterally. The ganglions showed a fusiform shape and reddish in color. The cranial cervical ganglion covered by the digastricus muscle. It lies in dorsal region of the base of epiglottic cartilage, ventromedial to tympanic bulla and ventrally to atlantic fossa, and medial of the occipital artery. This study showed that the cranial cervical ganglions in river buffalo were well-developed structure. The main branches of cranial cervical ganglion included the internal carotid, external carotid and jugular nerves.

3D Printed, Customized Cranial Implant for Surgical Planning

Science.gov (United States)

Bogu, Venkata Phanindra; Ravi Kumar, Yennam; Asit Kumar, Khanra

2018-06-01

The main objective of the present work is to model cranial implant and printed in FDM machine (printer model used: mojo). Actually this is peculiar case and the skull has been damaged in frontal, parietal and temporal regions and a small portion of frontal region damaged away from saggital plane, complexity is to fill this frontal region with proper curvature. The Patient CT-data (Number of slices was 381 and thickness of each slice is 0.488 mm) was processed in mimics14.1 software, mimics file was sent to 3-matic software and calculated thickness of skull at different sections where cranial implant is needed then corrected the edges of cranial implant to overcome CSF (cerebrospinal fluid) leakage and proper fitting. Finally the implant average thickness is decided as 2.5 mm and printed in FDM machine with ABS plastic.

Impaired spatial processing in a mouse model of fragile X syndrome.

Science.gov (United States)

Ghilan, Mohamed; Bettio, Luis E B; Noonan, Athena; Brocardo, Patricia S; Gil-Mohapel, Joana; Christie, Brian R

2018-05-17

Fragile X syndrome (FXS) is the most common form of inherited intellectual impairment. The Fmr1 -/y mouse model has been previously shown to have deficits in context discrimination tasks but not in the elevated plus-maze. To further characterize this FXS mouse model and determine whether hippocampal-mediated behaviours are affected in these mice, dentate gyrus (DG)-dependent spatial processing and Cornu ammonis 1 (CA1)-dependent temporal order discrimination tasks were evaluated. In agreement with previous findings of long-term potentiation deficits in the DG of this transgenic model of FXS, the results reported here demonstrate that Fmr1 -/y mice perform poorly in the DG-dependent metric change spatial processing task. However, Fmr1 -/y mice did not present deficits in the CA1-dependent temporal order discrimination task, and were able to remember the order in which objects were presented to them to the same extent as their wild-type littermate controls. These data suggest that the previously reported subregional-specific differences in hippocampal synaptic plasticity observed in the Fmr1 -/y mouse model may manifest as selective behavioural deficits in hippocampal-dependent tasks. Crown Copyright © 2018. Published by Elsevier B.V. All rights reserved.

Lessons learned using different mouse models during space radiation-induced lung tumorigenesis experiments.

Science.gov (United States)

Wang, Jian; Zhang, Xiangming; Wang, Ping; Wang, Xiang; Farris, Alton B; Wang, Ya

2016-06-01

Unlike terrestrial ionizing radiation, space radiation, especially galactic cosmic rays (GCR), contains high energy charged (HZE) particles with high linear energy transfer (LET). Due to a lack of epidemiologic data for high-LET radiation exposure, it is highly uncertain how high the carcinogenesis risk is for astronauts following exposure to space radiation during space missions. Therefore, using mouse models is necessary to evaluate the risk of space radiation-induced tumorigenesis; however, which mouse model is better for these studies remains uncertain. Since lung tumorigenesis is the leading cause of cancer death among both men and women, and low-LET radiation exposure increases human lung carcinogenesis, evaluating space radiation-induced lung tumorigenesis is critical to enable safe Mars missions. Here, by comparing lung tumorigenesis obtained from different mouse strains, as well as miR-21 in lung tissue/tumors and serum, we believe that wild type mice with a low spontaneous tumorigenesis background are ideal for evaluating the risk of space radiation-induced lung tumorigenesis, and circulating miR-21 from such mice model might be used as a biomarker for predicting the risk. Copyright © 2016 The Committee on Space Research (COSPAR). Published by Elsevier Ltd. All rights reserved.

Rasagiline ameliorates olfactory deficits in an alpha-synuclein mouse model of Parkinson's disease.

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Géraldine H Petit

Full Text Available Impaired olfaction is an early pre-motor symptom of Parkinson's disease. The neuropathology underlying olfactory dysfunction in Parkinson's disease is unknown, however α-synuclein accumulation/aggregation and altered neurogenesis might play a role. We characterized olfactory deficits in a transgenic mouse model of Parkinson's disease expressing human wild-type α-synuclein under the control of the mouse α-synuclein promoter. Preliminary clinical observations suggest that rasagiline, a monoamine oxidase-B inhibitor, improves olfaction in Parkinson's disease. We therefore examined whether rasagiline ameliorates olfactory deficits in this Parkinson's disease model and investigated the role of olfactory bulb neurogenesis. α-Synuclein mice were progressively impaired in their ability to detect odors, to discriminate between odors, and exhibited alterations in short-term olfactory memory. Rasagiline treatment rescued odor detection and odor discrimination abilities. However, rasagiline did not affect short-term olfactory memory. Finally, olfactory changes were not coupled to alterations in olfactory bulb neurogenesis. We conclude that rasagiline reverses select olfactory deficits in a transgenic mouse model of Parkinson's disease. The findings correlate with preliminary clinical observations suggesting that rasagiline ameliorates olfactory deficits in Parkinson's disease.

Ocular Albinism Type 1 Regulates Melanogenesis in Mouse Melanocytes

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Tianzhi Chen

2016-09-01

Full Text Available To investigate whether ocular albinism type 1 (OA1 is differentially expressed in the skin of mice with different coat colors and to determine its correlation with coat color establishment in mouse, the expression patterns and tissue distribution characterization of OA1 in the skin of mice with different coat colors were qualitatively and quantitatively analyzed by real-time quantitative PCR (qRT-PCR, immunofluorescence staining and Western blot. The qRT-PCR analysis revealed that OA1 mRNA was expressed in all mice skin samples tested, with the highest expression level in brown skin, a moderate expression level in black skin and the lowest expression level in gray skin. Positive OA1 protein bands were also detected in all skin samples by Western blot analysis. The relative expression levels of OA1 protein in both black and brown skin were significantly higher than that in gray skin, but there was no significant difference between black and brown mice. Immunofluorescence assays revealed that OA1 was mainly expressed in the hair follicle matrix, the inner and outer root sheath in the skin tissues with different coat colors. To get further insight into the important role of OA1 in the melanocytes’ pigmentation, we transfected the OA1 into mouse melanocytes and then detected the relative expression levels of pigmentation-related gene. Simultaneously, we tested the melanin content of melanocytes. As a result, the overexpression of OA1 significantly increased the expression levels of microphthalmia-associated transcription factor (MITF, tyrosinase (TYR, tyrosinase-related protein 1 (TRP1 and premelanosome protein (PMEL. However, the tyrosinase-related protein 2 (TRP2 level was attenuated. By contrast, the level of glycoprotein non-metastatic melanoma protein b (GPNMB was unaffected by OA1 overexpression. Furthermore, we observed a significant increase in melanin content in mouse melanocyte transfected OA1. Therefore, we propose that OA1 may

Transmission Properties of Human PrP 102L Prions Challenge the Relevance of Mouse Models of GSS.

Science.gov (United States)

Asante, Emmanuel A; Grimshaw, Andrew; Smidak, Michelle; Jakubcova, Tatiana; Tomlinson, Andrew; Jeelani, Asif; Hamdan, Shyma; Powell, Caroline; Joiner, Susan; Linehan, Jacqueline M; Brandner, Sebastian; Wadsworth, Jonathan D F; Collinge, John

2015-07-01

Inherited prion disease (IPD) is caused by autosomal-dominant pathogenic mutations in the human prion protein (PrP) gene (PRNP). A proline to leucine substitution at PrP residue 102 (P102L) is classically associated with Gerstmann-Sträussler-Scheinker (GSS) disease but shows marked clinical and neuropathological variability within kindreds that may be caused by variable propagation of distinct prion strains generated from either PrP 102L or wild type PrP. To-date the transmission properties of prions propagated in P102L patients remain ill-defined. Multiple mouse models of GSS have focused on mutating the corresponding residue of murine PrP (P101L), however murine PrP 101L, a novel PrP primary structure, may not have the repertoire of pathogenic prion conformations necessary to accurately model the human disease. Here we describe the transmission properties of prions generated in human PrP 102L expressing transgenic mice that were generated after primary challenge with ex vivo human GSS P102L or classical CJD prions. We show that distinct strains of prions were generated in these mice dependent upon source of the inoculum (either GSS P102L or CJD brain) and have designated these GSS-102L and CJD-102L prions, respectively. GSS-102L prions have transmission properties distinct from all prion strains seen in sporadic and acquired human prion disease. Significantly, GSS-102L prions appear incapable of transmitting disease to conventional mice expressing wild type mouse PrP, which contrasts strikingly with the reported transmission properties of prions generated in GSS P102L-challenged mice expressing mouse PrP 101L. We conclude that future transgenic modeling of IPDs should focus exclusively on expression of mutant human PrP, as other approaches may generate novel experimental prion strains that are unrelated to human disease.

Patient Satisfaction and Short-Term Outcome in Elective Cranial Neurosurgery.

Science.gov (United States)

Reponen, Elina; Tuominen, Hanna; Hernesniemi, Juha; Korja, Miikka

2015-11-01

Patient-reported experience is often used as a measure for quality of care, but no reports on patient satisfaction after cranial neurosurgery exist. To study the association of overall patient satisfaction and surgical outcome and to evaluate the applicability of overall patient satisfaction as a proxy for quality of care in elective cranial neurosurgery. We conducted an observational study on the relationship of overall patient satisfaction at 30 postoperative days with surgical and functional outcome (modified Rankin Scale [mRS] score) in a prospective, consecutive, and unselected cohort of 418 adult elective craniotomy patients enrolled between December 2011 and December 2012 at Helsinki University Hospital, Helsinki, Finland. Postoperative overall (subjective and objective) morbidity was present in 194 (46.4%) patients; yet almost 94% of all study patients reported high overall satisfaction. Low overall patient satisfaction at 30 days was not associated with postoperative major morbidity in elective cranial neurosurgery. Dependent functional status (mRS score ≥3) at 30 days, minor infections, poor postoperative subjective overall health status, and patient-reported severe symptoms (double vision, poor balance) may contribute to unsatisfactory patient experience. Overall patient satisfaction with elective cranial neurosurgery is high. Even 9 of 10 patients with postoperative major morbidity rated high overall patient satisfaction at 30 days. Overall patient satisfaction may merely reflect patient experience and subjective postoperative health status, and therefore it is a poor proxy for quality of care in elective cranial neurosurgery.

A Caenorhabditis elegans wild type defies the temperature-size rule owing to a single nucleotide polymorphism in tra-3.

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Jan E Kammenga

2007-03-01

Full Text Available Ectotherms rely for their body heat on surrounding temperatures. A key question in biology is why most ectotherms mature at a larger size at lower temperatures, a phenomenon known as the temperature-size rule. Since temperature affects virtually all processes in a living organism, current theories to explain this phenomenon are diverse and complex and assert often from opposing assumptions. Although widely studied, the molecular genetic control of the temperature-size rule is unknown. We found that the Caenorhabditis elegans wild-type N2 complied with the temperature-size rule, whereas wild-type CB4856 defied it. Using a candidate gene approach based on an N2 x CB4856 recombinant inbred panel in combination with mutant analysis, complementation, and transgenic studies, we show that a single nucleotide polymorphism in tra-3 leads to mutation F96L in the encoded calpain-like protease. This mutation attenuates the ability of CB4856 to grow larger at low temperature. Homology modelling predicts that F96L reduces TRA-3 activity by destabilizing the DII-A domain. The data show that size adaptation of ectotherms to temperature changes may be less complex than previously thought because a subtle wild-type polymorphism modulates the temperature responsiveness of body size. These findings provide a novel step toward the molecular understanding of the temperature-size rule, which has puzzled biologists for decades.

Mouse adhalin

DEFF Research Database (Denmark)

Liu, L; Vachon, P H; Kuang, W

1997-01-01

. To analyze the biological roles of adhalin, we cloned the mouse adhalin cDNA, raised peptide-specific antibodies to its cytoplasmic domain, and examined its expression and localization in vivo and in vitro. The mouse adhalin sequence was 80% identical to that of human, rabbit, and hamster. Adhalin...... was specifically expressed in striated muscle cells and their immediate precursors, and absent in many other cell types. Adhalin expression in embryonic mouse muscle was coincident with primary myogenesis. Its expression was found to be up-regulated at mRNA and protein levels during myogenic differentiation...

The putative oncogene Pim-1 in the mouse: its linkage and variation among t haplotypes.

Science.gov (United States)

Nadeau, J H; Phillips, S J

1987-11-01

Pim-1, a putative oncogene involved in T-cell lymphomagenesis, was mapped between the pseudo-alpha globin gene Hba-4ps and the alpha-crystallin gene Crya-1 on mouse chromosome 17 and therefore within the t complex. Pim-1 restriction fragment variants were identified among t haplotypes. Analysis of restriction fragment sizes obtained with 12 endonucleases demonstrated that the Pim-1 genes in some t haplotypes were indistinguishable from the sizes for the Pim-1b allele in BALB/c inbred mice. There are now three genes, Pim-1, Crya-1 and H-2 I-E, that vary among independently derived t haplotypes and that have indistinguishable alleles in t haplotypes and inbred strains. These genes are closely linked within the distal inversion of the t complex. Because it is unlikely that these variants arose independently in t haplotypes and their wild-type homologues, we propose that an exchange of chromosomal segments, probably through double crossingover, was responsible for indistinguishable Pim-1 genes shared by certain t haplotypes and their wild-type homologues. There was, however, no apparent association between variant alleles of these three genes among t haplotypes as would be expected if a single exchange introduced these alleles into t haplotypes. If these variant alleles can be shown to be identical to the wild-type allele, then lack of association suggests that multiple exchanges have occurred during the evolution of the t complex.

Distinctive behavioral and cellular responses to fluoxetine in the mouse model for Fragile X syndrome

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Marko eUutela

2014-05-01

Full Text Available Fluoxetine is used as a therapeutic agent for autism spectrum disorder (ASD, including Fragile X syndrome (FXS. The treatment often associates with disruptive behaviors such as agitation and disinhibited behaviors in FXS. To identify mechanisms that increase the risk to poor treatment outcome, we investigated the behavioral and cellular effects of fluoxetine on adult Fmr1 knockout (KO mice, a mouse model for FXS. We found that fluoxetine reduced anxiety-like behavior of both wild type and Fmr1 KO mice seen as shortened latency to enter the center area in the open field test. In Fmr1 KO mice, fluoxetine normalized locomotor hyperactivity but abnormally increased exploratory activity. Reduced Brain-derived neurotrophic factor (BDNF and increased TrkB receptor expression levels in the hippocampus of Fmr1 KO mice associated with inappropriate coping responses under stressful condition and abolished antidepressant activity of fluoxetine. Fluoxetine response in the cell proliferation was also missing in the hippocampus of Fmr1 KO mice when compared with wild type controls. The postnatal expression of serotonin transporter was reduced in the thalamic nuclei of Fmr1 KO mice during the time of transient innervation of somatosensory neurons suggesting that developmental changes of serotonin transporter (SERT expression were involved in the differential cellular and behavioral responses to fluoxetine in wild type and Fmr1 mice. The results indicate that changes of BDNF/TrkB signaling contribute to differential behavioral responses to fluoxetine among individuals with ASD.

[Cranial nerve palsy caused by tumours of the head and neck

NARCIS (Netherlands)

Delsing, C.P.; Verbist, B.M.; Hoogen, F.J.A. van den

2013-01-01

Cranial nerve palsy is a diagnostic guiding symptom, but often goes unrecognized. The differential diagnosis includes a variety of diseases, including malignant tumours of the head and neck. Here we describe three cases of cranial nerve palsy. In two of the cases the palsy was recognized following

Multi cranial nerve palsies as the presenting features of prostate carcinoma

International Nuclear Information System (INIS)

Mitchell, D.M.; Wynne, C.J.; Cowan, I.

2008-01-01

Full text: Cranial nerve palsies have previously been reported in metastatic prostate carcinoma, usually occurring late in the course of the disease. We describe the case of a 55-year-old man whose diagnosis of prostate cancer was made following investigation of multiple cranial nerve palsies.

GSK3 influences social preference and anxiety-related behaviors during social interaction in a mouse model of fragile X syndrome and autism.

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Marjelo A Mines

Full Text Available BACKGROUND: Nearly 1% of children in the United States exhibit autism spectrum disorders, but causes and treatments remain to be identified. Mice with deletion of the fragile X mental retardation 1 (Fmr1 gene are used to model autism because loss of Fmr1 gene function causes Fragile X Syndrome (FXS and many people with FXS exhibit autistic-like behaviors. Glycogen synthase kinase-3 (GSK3 is hyperactive in brains of Fmr1 knockout mice, and inhibition of GSK3 by lithium administration ameliorates some behavioral impairment in these mice. We extended our studies of this association by testing whether GSK3 contributes to socialization behaviors. This used two mouse models with disrupted regulation of GSK3, Fmr1 knockout mice and GSK3 knockin mice, in which inhibitory serines of the two isoforms of GSK3, GSK3alpha and GSK3beta, are mutated to alanines, leaving GSK3 fully active. METHODOLOGY/PRINCIPAL FINDINGS: To assess sociability, test mice were introduced to a restrained stimulus mouse (S1 for 10 min, followed by introduction of a second restrained stimulus mouse (S2 for 10 min, which assesses social preference. Fmr1 knockout and GSK3 knockin mice displayed no deficit in sociability with the S1 mouse, but unlike wild-type mice neither demonstrated social preference for the novel S2 mouse. Fmr1 knockout mice displayed more anxiety-related behaviors during social interaction (grooming, rearing, and digging than wild-type mice, which was ameliorated by inhibition of GSK3 with chronic lithium treatment. CONCLUSIONS/SIGNIFICANCE: These results indicate that impaired inhibitory regulation of GSK3 in Fmr1 knockout mice may contribute to some socialization deficits and that lithium treatment can ameliorate certain socialization impairments. As discussed in the present work, these results suggest a role for GSK3 in social behaviors and implicate inhibition of GSK3 as a potential therapeutic.

Vertical tears of the cranial horn of the meniscus and its cranial ligament in the equine femorotibial joint: 7 cases and their treatment by arthroscopic surgery.

Science.gov (United States)

Walmsley, J P

1995-01-01

Five horses with a vertical tear in the cranial horn and cranial ligament of the medial meniscus and 2 horses with a similar injury in the lateral meniscus were diagnosed from a series of 126 horses which were examined arthroscopically for stifle lameness. All the lesions had similar characteristics. The tear was about 1 cm from the axial border of the meniscus and its ligament and, in all but one case in which it was incomplete, much of the torn tissue was loosely attached in the axial part of the joint from where it was removed. The remaining meniscus, abaxial to the tear, was displaced cranially and abaxially and its torn edges were debrided. Radiographically, 6 cases had proliferative new bone on the cranial aspect of the intercondylar eminence of the tibia and 3 had calcified soft tissue densities in the cranial, medial or lateral femorotibial joint. Following surgery and a 6 month period of rest and controlled exercise, 3 horses returned to full competition work, one was usable for hacking, 2 are convalescing and one is lame after one year. It is postulated that this could be a characteristic meniscal injury in horses which can benefit from arthroscopic surgery. Better techniques for accessing the body and caudal pole of the menisci are needed if a more complete diagnosis and treatment of meniscal injuries are to be achieved.

Vertical tears of the cranial horn of the meniscus and its cranial ligament in the equine femorotibial joint: 7 cases and their treatment by arthroscopic surgery