SOD1, ANG, VAPB, TARDBP, and FUS Mutations in Familial Amyotrophic Lateral Sclerosis: Genotype-phenotype Correlations

Journal of Medical Genetics. Aug, 2010  |  Pubmed ID: 20577002

Mutations in SOD1, ANG, VAPB, TARDBP and FUS genes have been identified in amyotrophic lateral sclerosis (ALS).

Morbid Risk for Schizophrenia in First-degree Relatives of People with Frontotemporal Dementia

The British Journal of Psychiatry : the Journal of Mental Science. Jul, 2010  |  Pubmed ID: 20592430

Familial co-occurrence of frontotemporal dementia and schizophrenia has never been investigated.

CHMP2B Mutations Are Rare in French Families with Frontotemporal Lobar Degeneration

Journal of Neurology. Dec, 2010  |  Pubmed ID: 20625756

Two C-truncating CHMP2B (chromatin modifying protein 2B) mutations were recently found in Danish and Belgian families with autosomal dominant forms of frontotemporal lobar degeneration (FTLD). In addition, few CHMP2B missense mutations of uncertain pathogenic role were reported in several families with FTLD or FTLD associated with motoneuron disease (FTLD-MND). In order to determine the genetic contribution of CHMP2B mutations in FTLD and FTLD-MND families, we analyzed the CHMP2B gene in 198 French probands with familial FTLD and FTLD-MND. One CHMP2B missense variant was found in a proband with familial FTLD (0.8%). The pathogenic role of CHMP2B missense variants is unclear, however the pSer194Leu substitution, located in the C-terminal domain of the protein, was predicted to alter the stability of the protein by in silico analyses. We conclude that CHMP2B mutations represent a rare cause of familial FTLD and they are not implicated in familial FTLD-MND in French patients. The previously reported C-truncating CHMP2B mutations may be private to the Danish and Belgian pedigrees.

Liver Transplantation for Multiple Angiomyolipomas Complicating Tuberous Sclerosis Complex

Gastroentérologie Clinique Et Biologique. Sep, 2010  |  Pubmed ID: 20674202

Tuberous sclerosis complex is a genetic multisystem disorder characterised by widespread hamartomas in several organs, including the brain, heart, skin, eyes, kidney, lung, and liver. Hepatic multiple, bilateral angiomyolipomas are a rare and usually asymptomatic complication in patients with tuberous sclerosis. We report here the case of a patient who needed liver transplantation because of debilitating manifestations and mechanical complications of massive liver involvement by multiple angiomyolipomas (severe malnutrition, anorexia and abdominal pain). Seventeen tumors, from 2 to 16 cm in diameter, were identified at examination of the liver explant. No feature suggestive of malignant behaviour was identified at histological examination. In conclusion, this unusual indication of liver transplantation underlines the interest of this therapeutic approach for benign tumors for which the multiplicity of the lesions and their huge volume prevent any attempt at surgical resection.

Multifunctional Tumor-targeted Polymer-peptide-drug Delivery System for Treatment of Primary and Metastatic Cancers

Pharmaceutical Research. Nov, 2010  |  Pubmed ID: 20700631

In order to improve drug delivery to drug-resistant ovarian tumors, we constructed a multifunctional polymer-peptide-drug conjugate (PPDC) system for effective treatment of primary and metastatic ovarian cancers.

A Prospective Follow-up of Two 21/7 Cycles Followed by Two Extended Regimen 84/7 Cycles with Contraceptive Pills Containing Ethinyl Estradiol and Drospirenone

The Israel Medical Association Journal : IMAJ. Jul, 2010  |  Pubmed ID: 20862819

Continuous use of combined oral contraceptives is currently attracting growing interest as a means of improving menstrual related symptoms and reducing the number of bleeding days.

FUS Mutations in Frontotemporal Lobar Degeneration with Amyotrophic Lateral Sclerosis

Journal of Alzheimer's Disease : JAD. 2010  |  Pubmed ID: 21158017

Rapid advances were made in the knowledge of amyotrophic lateral sclerosis (ALS) with the recent identification of TARDBP and FUS mutations in familial ALS. More recently, FUS-positive inclusions were found in a subset of TDP-43-negative frontotemporal lobar degeneration (FTLD) prompting us to analyze FUS in FTLD and FTLD-ALS patients. The p.Arg521His mutation was identified in a patient who initially had behavioral disorders and rapidly developed ALS. Although the frequency of mutations is low, our study enlarges the phenotypes associated with FUS mutations and shows that FUS could also play a direct pathogenic role in FTLD spectrum of diseases.

Fronto-temporal Lobar Degeneration: Neuropathology in 60 Cases

Journal of Neural Transmission (Vienna, Austria : 1996). May, 2011  |  Pubmed ID: 21541771

Sixty cases of frontotemporal lobar degeneration (FTLD) were collected over 22 years. Brain weight was negatively correlated with disease duration. The neuronal and/or glial inclusions were labeled by anti-TDP, anti-FUS or anti-TAU antibodies, respectively, in 40, 3 and 12 cases. In the FTLD-TDP group, mutation of the progranulin gene was found in four cases (FTD-GRN), with nuclear, cat eye inclusions and severe neuronal loss in CA1 and subiculum. The motor neurons were involved in 27 cases (fronto-temporal dementia with amyotrophic lateral sclerosis = FTD-ALS). Familial FTD-ALS cases lived longer than sporadic ones. In nine cases, there was no ALS, no GRN mutation (FTD-NAP). The cases in the FTD-ALS and FTD-NAP subgroups were of Sampathu type 2 (TDP-positive inclusions located mostly in cell bodies and short neurites) with the exception of five cases which belonged to type 1 (long TDP-positive neurites in the superficial layers of the cortex). All of the FTLD-FUS of this series cases were affected by neuronal intermediate filament inclusion disease (NIFID). They were young. The survival was short. In the FTLD-tau group, mutations P301P (previously not recognized as pathogenic), P301L and S305N were identified. Pick disease (n = 5) appeared as a homogeneous sporadic disorder. The current nomenclature allows the neuropathological classification of nearly all the cases of FTD. The prevalence of the different types of FTD is tightly linked to the recruitment. This series was enriched in motor neuron disease (explaining the overall predominance of type 2 TDP inclusions).

Management of the Malpositioned Levonorgestrel-releasing Intrauterine System

Contraception. Oct, 2011  |  Pubmed ID: 22036043

BACKGROUND: The management of a malpositioned levonorgestrel (LNG)-releasing intrauterine system (IUS) can present a clinical challenge, complicated by the high cost of replacing it with a new device. We tried to challenge the guidelines and common practice that usually suggest prompt removal of any malpositioned IUS and replacement with a new one. STUDY DESIGN: We present our experience with 18 patients in whom the LNG-releasing IUS was found during a routine sonographic evaluation to be displaced towards the cervical canal 2 to 36 months postinsertion. Using an alligator forceps, the device was repositioned in the uterine cavity. RESULTS: The procedure was deemed successful in 17 (94.4%) of 18 cases. In 3 (17.6%) of the 17 successful procedures, the LNG-releasing IUS was found again to be malpositioned within 2 months. No complications were noted, and no postprocedural infection occurred. CONCLUSION: Repositioning of a malpositioned LNG-releasing IUS should be considered, as it is an easy and simple manipulation that can be done in the office with a high success rate and minimal risk of complications.

SPIKE: a Database of Highly Curated Human Signaling Pathways

Nucleic Acids Research. Jan, 2011  |  Pubmed ID: 21097778

The rapid accumulation of knowledge on biological signaling pathways and their regulatory mechanisms has highlighted the need for specific repositories that can store, organize and allow retrieval of pathway information in a way that will be useful for the research community. SPIKE (Signaling Pathways Integrated Knowledge Engine; http://www.cs.tau.ac.il/&~spike/) is a database for achieving this goal, containing highly curated interactions for particular human pathways, along with literature-referenced information on the nature of each interaction. To make database population and pathway comprehension straightforward, a simple yet informative data model is used, and pathways are laid out as maps that reflect the curator’s understanding and make the utilization of the pathways easy. The database currently focuses primarily on pathways describing DNA damage response, cell cycle, programmed cell death and hearing related pathways. Pathways are regularly updated, and additional pathways are gradually added. The complete database and the individual maps are freely exportable in several formats. The database is accompanied by a stand-alone software tool for analysis and dynamic visualization of pathways.

The Autophagy Protein Atg12 Associates with Antiapoptotic Bcl-2 Family Members to Promote Mitochondrial Apoptosis

Molecular Cell. Dec, 2011  |  Pubmed ID: 22152474

Autophagy and apoptosis constitute important determinants of cell fate and engage in a complex interplay in both physiological and pathological settings. The molecular basis of this crosstalk is poorly understood and relies, in part, on "dual-function" proteins that operate in both processes. Here, we identify the essential autophagy protein Atg12 as a positive mediator of mitochondrial apoptosis and show that Atg12 directly regulates the apoptotic pathway by binding and inactivating prosurvival Bcl-2 family members, including Bcl-2 and Mcl-1. The binding occurs independently of Atg5 or Atg3 and requires a unique BH3-like motif in Atg12, characterized by interaction studies and computational docking. In apoptotic cells, knockdown of Atg12 inhibited Bax activation and cytochrome c release, while ectopic expression of Atg12 antagonized the antiapoptotic activity of Mcl-1. The interaction between Atg12 and Bcl-2 family members may thus constitute an important point of convergence between autophagy and apoptosis in response to specific signals.

A Genome-wide Study Reveals Rare CNVs Exclusive to Extreme Phenotypes of Alzheimer Disease

European Journal of Human Genetics : EJHG. Dec, 2011  |  Pubmed ID: 22166940

Studying rare extreme forms of Alzheimer disease (AD) may prove to be a useful strategy in identifying new genes involved in monogenic determinism of AD. Amyloid precursor protein (APP), PSEN1, and PSEN2 mutations account for only 85% of autosomal dominant early-onset AD (ADEOAD) families. We hypothesised that rare copy number variants (CNVs) could be involved in ADEOAD families without mutations in known genes, as well as in rare sporadic young-onset AD cases. Using high-resolution array comparative genomic hybridisation, we assessed the presence of rare CNVs in 21 unrelated ADEOAD cases, having no alteration on known genes, and 12 sporadic AD cases, with an age of onset younger than 55 years. The analysis revealed the presence of 7 singleton CNVs (4 in ADEOAD and 3 in sporadic cases) absent in 1078 controls and 912 late-onset AD cases. Strikingly, 4 out of 7 rearrangements target genes (KLK6, SLC30A3, MEOX2, and FPR2) encoding proteins that are tightly related to amyloid-β peptide metabolism or signalling. Although these variants are individually rare and restricted to particular subgroups of patients, these findings support the causal role, in human pathology, of a set of genes coding for molecules suspected for a long time to modify Aβ metabolism or signalling, and for which animal or cellular models have already been developed.European Journal of Human Genetics advance online publication, 14 December 2011; doi:10.1038/ejhg.2011.225.

Quantitative Assessment of the Evolution of Cerebellar Signs in Spinocerebellar Ataxias

Movement Disorders : Official Journal of the Movement Disorder Society. Feb, 2011  |  Pubmed ID: 21287600

Responsive ataxia rating scales are essential for determining outcome measures in clinical trials.

G303V Tau Mutation Presenting with Progressive Supranuclear Palsy-like Features

Movement Disorders : Official Journal of the Movement Disorder Society. Nov, 2011  |  Pubmed ID: 22109955

Dedifferentiation of Foetal CNS Stem Cells to Mesendoderm-like Cells Through an EMT Process

PloS One. 2012  |  Pubmed ID: 22276221

Tissue-specific stem cells are considered to have a limited differentiation potential. Recently, this notion was challenged by reports that showed a broader differentiation potential of neural stem cells, in vitro and in vivo, although the molecular mechanisms that regulate plasticity of neural stem cells are unknown. Here, we report that neural stem cells derived from mouse embryonic cortex respond to Lif and serum in vitro and undergo epithelial to mesenchymal transition (EMT)-mediated dedifferentiation process within 48 h, together with transient upregulation of pluripotency markers and, more notably, upregulation of mesendoderm genes, Brachyury (T) and Sox17. These induced putative mesendoderm cells were injected into early gastrulating chick embryos, which revealed that they integrated more efficiently into mesoderm and endoderm lineages compared to non-induced cells. We also found that TGFβ and Jak/Stat pathways are necessary but not sufficient for the induction of mesendodermal phenotype in neural stem cells. These results provide insights into the regulation of plasticity of neural stem cells through EMT. Dissecting the regulatory pathways involved in these processes may help to gain control over cell fate decisions.

[Incidental Finding of Phaeochromocytoma During Surgery: The Anaesthesiologist's Nightmare]

Annales Françaises D'anesthèsie Et De Rèanimation. Feb, 2012  |  Pubmed ID: 22285940

We report the case of a patient who presented hypertension paroxysmal with acute pulmonary oedema followed by cardiocirculatory arrest during gynaecological surgery for resection of latero-aortic lymph nodes suspected to be cervical cancer metastases. This intervention, originally oncologic, has discovered ectopic phaeochromocytoma a posteriori. The management of perioperative serious adverse events revealing the undiagnosed phaeochromocytoma is discussed.

Rethinking Mobile Delivery: Using Quick Response Codes to Access Information at the Point of Need

Medical Reference Services Quarterly. Jan, 2012  |  Pubmed ID: 22289092

This article covers the use of Quick Response (QR) codes to provide instant mobile access to information, digital collections, educational offerings, library website, subject guides, text messages, videos, and library personnel. The array of uses and the value of using QR codes to push customized information to patrons are explained. A case is developed for using QR codes for mobile delivery of customized information to patrons. Applications in use at the Libraries of the University of Utah will be reviewed to provide readers with ideas for use in their library.

Autosomal Recessive Cerebellar Ataxias with Oculomotor Apraxia

Handbook of Clinical Neurology / Edited by P.J. Vinken and G.W. Bruyn. 2012  |  Pubmed ID: 21827898

Application of Nanoparticles for the Detection and Sorting of Pathogenic Bacteria by Flow-cytometry

Advances in Experimental Medicine and Biology. 2012  |  Pubmed ID: 22101709

In this paper we will describe a new developed contribution of fluorescence nano-crystal (q-dots) as a fluorescence label for detecting pathogenic bacteria by flow cytometry (FCM) and the use of nano-magnetic particles to improve bacterial sorting by Flow cytometry cell sorting (FACS).FCM or FACS systems are based upon single cell detection by light scatter and Immunofluorescence labeling signals. The common FACS systems are based upon single or dual excitation as excitation source both for light scatter parameters and for several fluorescence detectors. Hence, for multi-labeling detection, there is a need for fluorophores with broad excitation wave length and sharp emission bands. Moreover, such fluorophores should be with high fluorescence efficiency, stable, and available for bio-molecules conjugation. Q-dots benefit from practical features which meet those -criteria. We will describe the use of q-dots as fluorescence labels for specific conjugates against Bacillus anthracis spores and Yersinia pestis bacteria, which enable the specific detection of the different species. A specific and sensitive multiplex analysis procedure for both pathogens was achieved, with high sensitivity down to 10(3) bacteria per ml in the sample.Sorting bacteria by FACS has a tremendous advantage for sensitive and selective analysis and sorting of sub-populations. However it has always been a difficult task due to the fact that bacteria are small particles (usually 1-3 μm). For such small particles, light scatter signal is on the threshold level, and many positive events may be lost. Here we will present the development of a procedure for sorting of the gram negative bacteria Y. pestis from environment samples. We will show that the application of nano-magnetic particles, as a tool for the immunomagnetic labeling and separation of the bacteria, enables fast sorting in high and low bacterial concentration down to 10  (5) cfu/ml. The nano-metric physical size of the immunospecific labeling particles disguises them from the FACS detectors; hence the bacterial population becomes the major population as opposed to being "rare events population" when using standard micro-magnetic beads for pre-enrichment.The procedure of separation and collection of bacteria enables sensitive detection and characterization methods of bacteria from complex samples.

Seasonal Changes of Macroinvertebrate Communities in a Stormwater Wetland Collecting Pesticide Runoff from a Vineyard Catchment (Alsace, France)

Archives of Environmental Contamination and Toxicology. Jan, 2012  |  Pubmed ID: 21656048

Agricultural land use may influence macroinvertebrate communities by way of pesticide contamination associated with agricultural runoff. However, information about the relation between runoff-related pesticides and communities of benthic macroinvertebrates in stormwater wetland that receive agricultural runoff does not currently exist. Here we show changes in macroinvertebrates communities of a stormwater wetland that collects pesticide-contaminated runoff from a vineyard catchment. Sixteen runoff-associated pesticides, including the insecticide flufenoxuron, were continuously quantified at the inlet of the stormwater wetland from April to September (period of pesticide application). In parallel, benthic macroinvertebrate communities, pesticide concentrations, and physicochemical parameters in the wetland were assessed twice a month. Twenty-eight contaminated runoffs ranging from 1.1 to 114 m3 entered the wetland during the study period. Flufenoxuron concentrations in runoff-suspended solids ranged from 1.5 to 18.5 μg kg(-1) and reached 6 μg kg(-1) in the wetland sediments. However, flufenoxuron could not be detected in water. The density, diversity, and abundance of macroinvertebrates largely varied over time. Redundancy and formal concept analyses showed that concentrations of flufenoxuron, vegetation cover, and flow conditions significantly determine the community structures of stormwater wetland macroinvertebrates. This study shows that flow conditions, vegetation cover, and runoff-related pesticides jointly affect communities of benthic macroinvertebrates in stormwater wetlands.