JoVE Visualize What is visualize?
Stop Reading. Start Watching.
Advanced Search
Stop Reading. Start Watching.
Regular Search
Find video protocols related to scientific articles indexed in Pubmed.
Cerebrospinal fluid level of YKL-40 protein in preclinical and prodromal Alzheimer's disease.
J. Alzheimers Dis.
PUBLISHED: 07-16-2014
Show Abstract
Hide Abstract
An increase in YKL-40 levels seems to correlate with disease severity and poor prognosis in many diseases, including several neurodegenerative diseases such as multiple sclerosis, amyotrophic lateral sclerosis, and Alzheimer's disease (AD). Specifically, YKL-40 protein is increased in mild AD with respect to controls, both in cerebrospinal fluid (CSF) and plasma.
Related JoVE Video
Polymorphic crystal structures of an all-AT DNA dodecamer.
Biopolymers
PUBLISHED: 07-04-2014
Show Abstract
Hide Abstract
In this work we explore the influence of different solvents and ions on the crystallization behavior of an all-AT dodecamer d(AATAAATTTATT)2. In all cases the oligonucleotides are found as continuous columns of stacked duplexes. The spatial organization of such columns is variable, consequently we have obtained seven different crystal forms. The duplexes can be made to crystallize in either parallel or crossed columns. Such versatility in the formation of a variety of crystal forms is characteristic for this sequence. It had not been previously reported for any other sequence. In all cases the oligonucleotide duplexes have been found to crystallize in the B form. The crystallization conditions determine the organization of the crystal, although no clear local interactions have been detected. Mg(2+) and Ni(2+) can be used in order to obtain compact crossed structures. DNA-DNA interactions in the crystals of our all-AT duplexes present crossovers which are different from those previously reported for mixed sequence oligonucleotides. Our results demonstrate that changes in the ionic atmosphere and the crystallization solvent have a strong influence on the DNA-DNA interactions. Similar ionic changes will certainly influence the biological activity of DNA. Modulation of the crystal structure by ions should also be explored in DNA crystal engineering. Liquid crystals with a peculiar macroscopic shape have also been observed.
Related JoVE Video
TREM2 mutations implicated in neurodegeneration impair cell surface transport and phagocytosis.
Sci Transl Med
PUBLISHED: 07-04-2014
Show Abstract
Hide Abstract
Genetic variants in the triggering receptor expressed on myeloid cells 2 (TREM2) have been linked to Nasu-Hakola disease, Alzheimer's disease (AD), Parkinson's disease, amyotrophic lateral sclerosis, frontotemporal dementia (FTD), and FTD-like syndrome without bone involvement. TREM2 is an innate immune receptor preferentially expressed by microglia and is involved in inflammation and phagocytosis. Whether and how TREM2 missense mutations affect TREM2 function is unclear. We report that missense mutations associated with FTD and FTD-like syndrome reduce TREM2 maturation, abolish shedding by ADAM proteases, and impair the phagocytic activity of TREM2-expressing cells. As a consequence of reduced shedding, TREM2 is virtually absent in the cerebrospinal fluid (CSF) and plasma of a patient with FTD-like syndrome. A decrease in soluble TREM2 was also observed in the CSF of patients with AD and FTD, further suggesting that reduced TREM2 function may contribute to increased risk for two neurodegenerative disorders.
Related JoVE Video
Early neuronal loss and axonal/presynaptic damage is associated with accelerated amyloid-? accumulation in A?PP/PS1 Alzheimer's disease mice subiculum.
J. Alzheimers Dis.
PUBLISHED: 06-15-2014
Show Abstract
Hide Abstract
The progressive cognitive decline leading to dementia in Alzheimer's disease (AD) patients is the consequence of a severe loss of synapses and neurons affecting particular cell subpopulations in selected brain areas, with the subiculum being one of the earliest regions displaying severe atrophy and pathology. The lack of significant neuronal loss in most AD models is, in fact, the major shortcoming for the preclinical evaluation of drugs that could have greater potential in patients to alleviate or prevent this disease. In this study, using immunohistochemical and stereological approaches, we have analyzed the histopathological events in the subiculum of A?PP751SwedLondon/PS1M146L mice, a transgenic model that displays neuronal vulnerability at early ages in hippocampus and entorhinal cortex. Our results indicate that the subiculum is the earliest affected region in the hippocampus, showing a selective early loss of both principal neurons (28%) and SOM-positive interneurons (69%). In addition, our data demonstrate the existence of an early axonal and synaptic pathology, which may represent the beginning of the synaptic disruption and loss. These neurodegenerative processes occur in parallel, and closely related, with the onset and accelerated progression of the extracellular amyloid-? deposition, thus suggesting plaques as major contributors of neuronal/axonal damage. Data reported here indicate that this AD model displays a selective AD-like neurodegenerative phenotype in highly vulnerable regions, including the subiculum, and therefore can be a very useful model for testing the therapeutic ability of potential compounds to protect neurons and ameliorate disease symptoms.
Related JoVE Video
Rivaroxaban for the treatment of venous thromboembolism. A "real-life" perspective in 103 patients.
Thromb. Res.
PUBLISHED: 05-06-2014
Show Abstract
Hide Abstract
Randomized clinical trials have demonstrated non-inferiority of rivaroxaban compared with vitamin K antagonists (VKAs) in the treatment of venous thromboembolism (VTE). Our objective was to analyze in real life, tolerance, recurrence, bleeding and adverse events of rivaroxaban in patients with acute symptomatic VTE.
Related JoVE Video
Investigation of the role of rare TREM2 variants in frontotemporal dementia subtypes.
Neurobiol. Aging
PUBLISHED: 04-28-2014
Show Abstract
Hide Abstract
Frontotemporal dementia (FTD) is a clinically and genetically heterogeneous disorder. Rare TREM2 variants have been recently identified in families affected by FTD-like phenotype. However, genetic studies of the role of rare TREM2 variants in FTD have generated conflicting results possibly because of difficulties on diagnostic accuracy. The aim of the present study was to investigate associations between rare TREM2 variants and specific FTD subtypes (FTD-S). The entire coding sequence of TREM2 was sequenced in FTD-S patients of Spanish (n = 539) and German (n = 63) origin. Genetic association was calculated using Fisher exact test. The minor allele frequency for controls was derived from in-house genotyping data and publicly available databases. Seven previously reported rare coding variants (p.A28V, p.W44X, p.R47H, p.R62H, p.T66M, p.T96K, and p.L211P) and 1 novel missense variant (p.A105T) were identified. The p.R47H variant was found in 4 patients with FTD-S. Two of these patients showed cerebrospinal fluid pattern of amyloid beta, tau, and phosphorylated-tau suggesting underlying Alzheimer's disease (AD) pathology. No association was found between p.R47H and FTD-S. A genetic association was found between p.T96K and FTD-S (p = 0.013, odds ratio = 4.23, 95% Confidence Interval [1.17-14.77]). All 6 p.T96K patients also carried the TREM2 variant p.L211P, suggesting linkage disequilibrium. The remaining TREM2 variants were found in 1 patient, respectively, and were absent in controls. The present findings provide evidence that p.T96K is associated with FTD-S and that p.L211P may contribute to its pathogenic effect. The data also suggest that p.R47H is associated with an FTD phenotype that is characterized by the presence of underlying AD pathology.
Related JoVE Video
Maintenance of immune tolerance by Foxp3(+) regulatory T cells requires CD69 expression.
J. Autoimmun.
PUBLISHED: 04-22-2014
Show Abstract
Hide Abstract
Although FoxP3(+) regulatory T cells are key players in the maintenance of immune tolerance and autoimmunity, the lack of specific markers constitute an obstacle to their use for immunotherapy protocols. In this study, we have investigated the role of the C-type lectin receptor CD69 in the suppressor function of Tregs and maintenance of immune tolerance towards harmless inhaled antigens. We identified a novel FoxP3(+)CD69(+) Treg subset capable to maintain immune tolerance and protect to developing inflammation. Although CD69(+) and CD69(-)FoxP3(+) Tregs exist in homeostasis, only CD69-expressing Tregs express high levels of CTLA-4, ICOS, CD38 and GITR suppression-associated markers, secrete high amounts of TGF? and have potent suppressor activity. This activity is regulated by STAT5 and ERK signaling pathways and is impaired by antibody-mediated down-regulation of CD69 expression. Moreover, immunotherapy with FoxP3(+)CD69(+) Tregs restores the homeostasis in Cd69(-/-) mice, that fail to induce tolerance, and is also highly proficient in the prevention of inflammation. The identification of the FoxP3(+)CD69(+) Treg subset paves the way toward the development of new therapeutic strategies to control immune homeostasis and autoimmunity.
Related JoVE Video
Single-port laparoscopic approach of the left liver: Initial experience.
Cir Esp
PUBLISHED: 03-19-2014
Show Abstract
Hide Abstract
New technological advances have enabled the development of single-port laparoscopic surgery. This approach began with cholecystectomy and subsequently with other abdominal surgeries. However, few publications on laparoscopic liver surgery have described the use of complete single-port access. We present our initial experience of a single-port laparoscopic hepatectomy.
Related JoVE Video
Usefulness of biomarkers in the diagnosis and prognosis of early-onset cognitive impairment.
J. Alzheimers Dis.
PUBLISHED: 03-01-2014
Show Abstract
Hide Abstract
Early-onset cognitive impairment diagnosis is often challenging due to the overlapping symptoms between the different degenerative and non-degenerative conditions. We aimed to evaluate the usefulness of cerebrospinal fluid (CSF) biomarkers in early-onset cognitive impairment differential diagnosis, to assess their contribution to the diagnosis of Alzheimer's disease (AD) based on the new National Institute of Aging-Alzheimer's Association (NIA-AA) workgroup's recommendations and their capacity to predict subsequent decline in early-onset mild cognitive impairment (MCI). 37 controls and 120 patients (clinical onset <65 years) with diagnosis based on criteria available in 2009 (51 MCI, 42 AD, 10 frontotemporal dementia (FTD), 3 posterior cortical atrophy, and 14 primary progressive aphasia (PPA)) were included. In addition, all subjects were also reclassified according to the revised criteria for MCI, AD, FTD, and PPA, excluding CSF data. We assessed the impact of adding the CSF data to the subject categorization according to the NIA-AA criteria. After inclusion of CSF results, 90% of amnestic and 82% of the non-amnestic AD presentation could be categorized as "high probability", while 3% of AD patients fit into the category "dementia probably not due to AD". All the 24 MCI patients who progressed to AD dementia and only 1/27 stable MCI presented pathological CSF at baseline. Only 4% of the FTD clinical diagnosis had pathological CSF levels. CSF biomarkers provide high diagnostic accuracy in a clinical context in differentiating AD, frontotemporal lobar degeneration, and controls in presenile subjects and can be used equally in amnestic and non-amnestic AD. Abnormal CSF-AD biomarker levels predict subsequent progression to AD dementia in subjects with early-onset MCI.
Related JoVE Video
Rare mutations in SQSTM1 modify susceptibility to frontotemporal lobar degeneration.
Acta Neuropathol.
PUBLISHED: 02-10-2014
Show Abstract
Hide Abstract
Mutations in the gene coding for Sequestosome 1 (SQSTM1) have been genetically associated with amyotrophic lateral sclerosis (ALS) and Paget disease of bone. In the present study, we analyzed the SQSTM1 coding sequence for mutations in an extended cohort of 1,808 patients with frontotemporal lobar degeneration (FTLD), ascertained within the European Early-Onset Dementia consortium. As control dataset, we sequenced 1,625 European control individuals and analyzed whole-exome sequence data of 2,274 German individuals (total n = 3,899). Association of rare SQSTM1 mutations was calculated in a meta-analysis of 4,332 FTLD and 10,240 control alleles. We identified 25 coding variants in FTLD patients of which 10 have not been described. Fifteen mutations were absent in the control individuals (carrier frequency <0.00026) whilst the others were rare in both patients and control individuals. When pooling all variants with a minor allele frequency <0.01, an overall frequency of 3.2 % was calculated in patients. Rare variant association analysis between patients and controls showed no difference over the whole protein, but suggested that rare mutations clustering in the UBA domain of SQSTM1 may influence disease susceptibility by doubling the risk for FTLD (RR = 2.18 [95 % CI 1.24-3.85]; corrected p value = 0.042). Detailed histopathology demonstrated that mutations in SQSTM1 associate with widespread neuronal and glial phospho-TDP-43 pathology. With this study, we provide further evidence for a putative role of rare mutations in SQSTM1 in the genetic etiology of FTLD and showed that, comparable to other FTLD/ALS genes, SQSTM1 mutations are associated with TDP-43 pathology.
Related JoVE Video
The antiprogestins mifepristone and onapristone reduce cell proliferation in the canine mammary carcinoma cell line CMT-U27.
Histol. Histopathol.
PUBLISHED: 02-06-2014
Show Abstract
Hide Abstract
Canine mammary tumours (CMTs) represent nearly half of all tumours in female dogs and some 50% have malignant behaviour. Simple epithelial carcinomas have shorter disease free periods after surgery and a higher reduction of the proliferation index reduction after antiprogestin aglepristone treatment in vivo related to the expression of progesterone receptors (PR). These findings make simple carcinomas good candidates for endocrine therapy. To further explore this possibility, the effects of the antiprogestins mifepristone (RU486) and onapristone (ZK299) on cell viability and PR expression of the canine mammary carcinoma cell line isolated from a simple epithelial carcinoma CMT-U27 were studied. Twenty five percent of CMT-U27 control cells expressed PR. RU486 (p<0.05) and ZK299 (p<0.05) reduced the number of viable cells (WST-8 test) at 24h but only the latter treatment reduced significantly PR expression in viable tumour cells at 24h of incubation. The results suggest that both RU486 and ZK299 induce a decrease in the number of viable CMT-U27 tumour cells with different effects on PR expression. The canine mammary carcinoma cell line CMT-U27 is sensitive to the effects of antiprogestins and may serve to further explore the role of these drugs in canine mammary carcinomas.
Related JoVE Video
TMEM106B is a genetic modifier of frontotemporal lobar degeneration with C9orf72 hexanucleotide repeat expansions.
Acta Neuropathol.
PUBLISHED: 01-19-2014
Show Abstract
Hide Abstract
Hexanucleotide repeat expansions in chromosome 9 open reading frame 72 (C9orf72) have recently been linked to frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis, and may be the most common genetic cause of both neurodegenerative diseases. Genetic variants at TMEM106B influence risk for the most common neuropathological subtype of FTLD, characterized by inclusions of TAR DNA-binding protein of 43 kDa (FTLD-TDP). Previous reports have shown that TMEM106B is a genetic modifier of FTLD-TDP caused by progranulin (GRN) mutations, with the major (risk) allele of rs1990622 associating with earlier age at onset of disease. Here, we report that rs1990622 genotype affects age at death in a single-site discovery cohort of FTLD patients with C9orf72 expansions (n = 14), with the major allele correlated with later age at death (p = 0.024). We replicate this modifier effect in a 30-site international neuropathological cohort of FTLD-TDP patients with C9orf72 expansions (n = 75), again finding that the major allele associates with later age at death (p = 0.016), as well as later age at onset (p = 0.019). In contrast, TMEM106B genotype does not affect age at onset or death in 241 FTLD-TDP cases negative for GRN mutations or C9orf72 expansions. Thus, TMEM106B is a genetic modifier of FTLD with C9orf72 expansions. Intriguingly, the genotype that confers increased risk for developing FTLD-TDP (major, or T, allele of rs1990622) is associated with later age at onset and death in C9orf72 expansion carriers, providing an example of sign epistasis in human neurodegenerative disease.
Related JoVE Video
Postsynaptic GABAB receptor activity regulates excitatory neuronal architecture and spatial memory.
J. Neurosci.
PUBLISHED: 01-17-2014
Show Abstract
Hide Abstract
Cognitive dysfunction is a common symptom in many neuropsychiatric disorders and directly correlates with poor patient outcomes. The majority of prolonged inhibitory signaling in the brain is mediated via GABAB receptors (GABABRs), but the molecular function of these receptors in cognition is ill defined. To explore the significance of GABABRs in neuronal activity and cognition, we created mice with enhanced postsynaptic GABABR signaling by mutating the serine 783 in receptor R2 subunit (S783A), which decreased GABABR degradation. Enhanced GABABR activity reduced the expression of immediate-early gene-encoded protein Arc/Arg3.1, effectors that are critical for long-lasting memory. Intriguingly, S783A mice exhibited increased numbers of excitatory synapses and surface AMPA receptors, effects that are consistent with decreased Arc/Arg3.1 expression. These deficits in Arc/Arg3.1 and neuronal morphology lead to a deficit in spatial memory consolidation. Collectively our results suggest a novel and unappreciated role for GABABR activity in determining excitatory neuronal architecture and spatial memory via their ability to regulate Arc/Arg3.1.
Related JoVE Video
Large APP locus duplication in a sporadic case of cerebral haemorrhage.
Neurogenetics
PUBLISHED: 01-14-2014
Show Abstract
Hide Abstract
We report a 54-year-old man who was admitted to the hospital because of acute neurological symptoms due to a cerebral haemorrhage. Postmortem brain examination revealed a lobar haemorrhage and advanced AD neuropathologic changes associated with severe cerebral amyloid angiopathy. Genetic study evidenced the presence of a large APP locus duplication (APPdup) in the patient and a PSEN1 p.E318G polymorphism in him and his older asymptomatic sibling. The APPdup spanned 14.5 Mb and blocks of segmental duplications were detected in the breakpoints. We propose the replication-based mechanism of Fork Stalling Template Switching (FoSTeS) to explain this APPdup rearrangement.
Related JoVE Video
Increased expression of insulin-like growth factor-1 receptor is correlated with worse survival in canine appendicular osteosarcoma.
Vet. J.
PUBLISHED: 01-13-2014
Show Abstract
Hide Abstract
Insulin-like growth factor 1 receptor (IGF-1R) is a cell membrane receptor widely expressed in tissues and involved in different cancers in humans. IGF-1R expression in human osteosarcoma has been associated with the development of tumour metastasis and with prognosis, and represents an attractive therapeutic target. The goal of this study was to investigate the expression of IGF-1R in canine osteosarcoma tissues and cell lines and assess its role and prognostic value. Samples from 34 dogs were examined by immunohistochemistry for IGF-1R expression. IGF-1R/AKT/MAPK signalling was evaluated by western blot and quantitative polymerase chain reaction in the cell lines. In addition, the in vitro inhibition of IGF-1R with pycropodophillin (PPP) was used to evaluate molecular and biological effects. Immunohistochemical data showed that IGF-1R was expressed in 71% of the analysed osteosarcoma samples and that dogs with higher levels of IGF-IR expression (47% of cases) had decreased survival (P?
Related JoVE Video
Recent advancements to study flowering time in almond and other Prunus species.
Front Plant Sci
PUBLISHED: 01-01-2014
Show Abstract
Hide Abstract
Flowering time is an important agronomic trait in almond since it is decisive to avoid the late frosts that affect production in early flowering cultivars. Evaluation of this complex trait is a long process because of the prolonged juvenile period of trees and the influence of environmental conditions affecting gene expression year by year. Consequently, flowering time has to be studied for several years to have statistical significant results. This trait is the result of the interaction between chilling and heat requirements. Flowering time is a polygenic trait with high heritability, although a major gene Late blooming (Lb) was described in "Tardy Nonpareil." Molecular studies at DNA level confirmed this polygenic nature identifying several genome regions (Quantitative Trait Loci, QTL) involved. Studies about regulation of gene expression are scarcer although several transcription factors have been described as responsible for flowering time. From the metabolomic point of view, the integrated analysis of the mechanisms of accumulation of cyanogenic glucosides and flowering regulation through transcription factors open new possibilities in the analysis of this complex trait in almond and in other Prunus species (apricot, cherry, peach, plum). New opportunities are arising from the integration of recent advancements including phenotypic, genetic, genomic, transcriptomic, and metabolomics studies from the beginning of dormancy until flowering.
Related JoVE Video
Neurodegenerative disorder risk in idiopathic REM sleep behavior disorder: study in 174 patients.
PLoS ONE
PUBLISHED: 01-01-2014
Show Abstract
Hide Abstract
To estimate the risk for developing a defined neurodegenerative syndrome in a large cohort of idiopathic REM sleep behavior disorder (IRBD) patients with long follow-up.
Related JoVE Video
Plasma phosphorylated TDP-43 levels are elevated in patients with frontotemporal dementia carrying a C9orf72 repeat expansion or a GRN mutation.
J. Neurol. Neurosurg. Psychiatr.
PUBLISHED: 12-04-2013
Show Abstract
Hide Abstract
About a half of patients with frontotemporal dementia (FTD) has deposition of phosphorylated TDP-43 protein (pTDP-43) in the brain. We studied pTDP-43 and total TDP-43 levels in plasma and cerebrospinal fluid (CSF) in healthy controls and patients with FTD, including those carrying a repeat expansion in the C9orf72 gene or a mutation in GRN.
Related JoVE Video
In vivo modification of Abeta plaque toxicity as a novel neuroprotective lithium-mediated therapy for Alzheimers disease pathology.
Acta Neuropathol Commun
PUBLISHED: 11-07-2013
Show Abstract
Hide Abstract
Alzheimers disease (AD) is characterized by the abnormal accumulation of extracellular beta-amyloid (Abeta) plaques, intracellular hyperphosphorylated tau, progressive synaptic alterations, axonal dystrophies, neuronal loss and the deterioration of cognitive capabilities of patients. However, no effective disease-modifying treatment has been yet developed. In this work we have evaluated whether chronic lithium treatment could ameliorate the neuropathology evolution of our well characterized PS1M146LxAPPSwe-London mice model.
Related JoVE Video
The foot posture index: anthropometric determinants and influence of sex.
J Am Podiatr Med Assoc
PUBLISHED: 09-28-2013
Show Abstract
Hide Abstract
The Foot Posture Index (FPI) quantifies foot posture on the basis of six criteria. Although the male foot is longer and broader than the female foot, limited evidence exists about the differences in foot posture between the sexes and which are its biological and anthropometric determinants. We sought to evaluate possible sex differences in the FPI and the determinants influencing foot posture.
Related JoVE Video
The ability of BDNF to modify neurogenesis and depressive-like behaviors is dependent upon phosphorylation of tyrosine residues 365/367 in the GABA(A)-receptor ?2 subunit.
J. Neurosci.
PUBLISHED: 09-27-2013
Show Abstract
Hide Abstract
Brain-derived neurotrophic factor (BDNF) is a potent regulator of neuronal activity, neurogenesis, and depressive-like behaviors; however, downstream effectors by which BDNF exerts these varying actions remain to be determined. Here we reveal that BDNF induces long-lasting enhancements in the efficacy of synaptic inhibition by stabilizing ?2 subunit-containing GABA(A) receptors (GABA(A)Rs) at the cell surface, leading to persistent reductions in neuronal excitability. This effect is dependent upon enhanced phosphorylation of tyrosines 365 and 367 (Y365/7) in the GABA(A)R ?2 subunit as revealed using mice in which these residues have been mutated to phenyalanines (Y365/7F). Heterozygotes for this mutation exhibit an antidepressant-like phenotype, as shown using behavioral-despair models of depression. In addition, heterozygous Y365/7F mice show increased levels of hippocampal neurogenesis, which has been strongly connected with antidepressant action. Both the antidepressant phenotype and the increased neurogenesis seen in these mice are insensitive to further modulation by BDNF, which produces robust antidepressant-like activity and neurogenesis in wild-type mice. Collectively, our results suggest a critical role for GABA(A)R ?2 subunit Y365/7 phosphorylation and function in regulating the effects of BDNF.
Related JoVE Video
Characterization of the repeat expansion size in C9orf72 in amyotrophic lateral sclerosis and frontotemporal dementia.
Hum. Mol. Genet.
PUBLISHED: 09-20-2013
Show Abstract
Hide Abstract
Hexanucleotide repeat expansions within the C9orf72 gene are the most important genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). The difficulty of developing a precise method to determine the expansion size has hampered the study of possible correlations between the hexanucleotide repeat number and clinical phenotype. Here we characterize, through a new non-radioactive Southern blot protocol, the expansion size range in a series of 38 ALS and 22 FTD heterozygous carriers of >30 copies of the repeat. Maximum, median and modal hexanucleotide repeat number were higher in ALS patients than in FTD patients (P< 0.05 in all comparisons). A higher median number of repeats correlated with a bigger range of repeat sizes (Spearmans ? = 0.743, P = 1.05 × 10(-11)). We did not find any correlation between age of onset or disease duration with the repeat size in neither ALS nor FTD mutation carriers. Clinical presentation (bulbar or spinal) in ALS patients did not correlate either with the repeat length. We finally analyzed two families with affected and unaffected repeat expansion carriers, compared the size of the repeat expansion between two monozygotic (MZ) twins (one affected of ALS and the other unaffected), and examined the expansion size in two different tissues (cerebellum and peripheral blood) belonging to the same FTD patient. The results suggested that the length of the C9orf72 repeat varies between family members, including MZ twins, and among different tissues from the same individual.
Related JoVE Video
Related JoVE Video
Tyrosine phosphorylation of GABAA receptor ?2-subunit regulates tonic and phasic inhibition in the thalamus.
J. Neurosci.
PUBLISHED: 08-02-2013
Show Abstract
Hide Abstract
GABA-mediated tonic and phasic inhibition of thalamic relay neurons of the dorsal lateral geniculate nucleus (dLGN) was studied after ablating tyrosine (Y) phosphorylation of receptor ?2-subunits. As phosphorylation of ?2 Y365 and Y367 reduces receptor internalization, to understand their importance for inhibition we created a knock-in mouse in which these residues are replaced by phenylalanines. On comparing wild-type (WT) and ?2(Y365/367F)+/- (HT) animals (homozygotes are not viable in utero), the expression levels of GABAA receptor ?4-subunits were increased in the thalamus of female, but not male mice. Raised ?-subunit expression levels were also observed in female ?2(Y365/367F) +/- thalamus. Electrophysiological analyses revealed no difference in the level of inhibition in male WT and HT dLGN, while both the spontaneous inhibitory postsynaptic activity and the tonic current were significantly augmented in female HT relay cells. The sensitivity of tonic currents to the ?-subunit superagonist THIP, and the blocker Zn(2+), were higher in female HT relay cells. This is consistent with upregulation of extrasynaptic GABAA receptors containing ?4- and ?-subunits to enhance tonic inhibition. In contrast, the sensitivity of GABAA receptors mediating inhibition in the female ?2(Y356/367F) +/- to neurosteroids was markedly reduced compared with WT. We conclude that disrupting tyrosine phosphorylation of the ?2-subunit activates a sex-specific increase in tonic inhibition, and this most likely reflects a genomic-based compensation mechanism for the reduced neurosteroid sensitivity of inhibition measured in female HT relay neurons.
Related JoVE Video
Assessing the role of the TREM2 p.R47H variant as a risk factor for Alzheimers disease and frontotemporal dementia.
Neurobiol. Aging
PUBLISHED: 05-08-2013
Show Abstract
Hide Abstract
A non-synonymous genetic rare variant, rs75932628-T (p.R47H), in the TREM2 gene has recently been reported to be a strong genetic risk factor for Alzheimers disease (AD). Also, rare recessive mutations have been associated with frontotemporal dementia (FTD). We aimed to investigate the role of p.R47H variant in AD and FTD through a multi-center study comprising 3172 AD and 682 FTD patients and 2169 healthy controls from Spain. We found that 0.6% of AD patients carried this variant compared to 0.1% of controls (odds ratio [OR] = 4.12, 95% confidence interval [CI] = 1.21-14.00, p = 0.014). A meta-analysis comprising 32,598 subjects from 4 previous studies demonstrated the large effect of the p.R47H variant in AD risk (OR = 4.11, 95% CI = 2.99-5.68, p = 5.27×10(-18)). We did not find an association between p.R47H and age of onset of AD or family history of dementia. Finally, none of the FTD patients harbored this genetic variant. These data strongly support the important role of p.R47H in AD risk, and suggest that this rare genetic variant is not related to FTD.
Related JoVE Video
Enhanced tonic inhibition influences the hypnotic and amnestic actions of the intravenous anesthetics etomidate and propofol.
J. Neurosci.
PUBLISHED: 04-26-2013
Show Abstract
Hide Abstract
Intravenous anesthetics exert a component of their actions via potentiating inhibitory neurotransmission mediated by ?-aminobutyric type-A receptors (GABAARs). Phasic and tonic inhibition is mediated by distinct populations of GABAARs, with the majority of phasic inhibition by subtypes composed of ?1-3??2 subunits, whereas tonic inhibition is dependent on subtypes assembled from ?4-6?? subunits. To explore the contribution that these distinct forms of inhibition play in mediating intravenous anesthesia, we have used mice in which tyrosine residues 365/7 within the ?2 subunit are mutated to phenyalanines (Y365/7F). Here we demonstrate that this mutation leads to increased accumulation of the ?4 subunit containing GABAARs in the thalamus and dentate gyrus of female Y365/7F but not male Y365/7F mice. Y365/7F mice exhibited a gender-specific enhancement of tonic inhibition in the dentate gyrus that was more sensitive to modulation by the anesthetic etomidate, together with a deficit in long-term potentiation. Consistent with this, female Y365/7F, but not male Y365/7F, mice exhibited a dramatic increase in the duration of etomidate- and propofol-mediated hypnosis. Moreover, the amnestic actions of etomidate were selectively potentiated in female Y365/7F mice. Collectively, these observations suggest that potentiation of tonic inhibition mediated by ?4 subunit containing GABAARs contributes to the hypnotic and amnestic actions of the intravenous anesthetics, etomidate and propofol.
Related JoVE Video
Neurodegenerative disease status and post-mortem pathology in idiopathic rapid-eye-movement sleep behaviour disorder: an observational cohort study.
Lancet Neurol
PUBLISHED: 04-03-2013
Show Abstract
Hide Abstract
We postulated that idiopathic rapid-eye-movement (REM) sleep behaviour disorder (IRBD) represents the prodromal phase of a Lewy body disorder and that, with sufficient follow-up, most cases would eventually be diagnosed with a clinical defined Lewy body disorder, such as Parkinsons disease (PD) or dementia with Lewy bodies (DLB).
Related JoVE Video
The effect of moderate running on foot posture index and plantar pressure distribution in male recreational runners.
J Am Podiatr Med Assoc
PUBLISHED: 03-29-2013
Show Abstract
Hide Abstract
Fatigue due to running has been shown to contribute to changes in plantar pressure distribution. However, little is known about changes in foot posture after running. We sought to compare the foot posture index before and after moderate exercise and to relate any changes to plantar pressure patterns.
Related JoVE Video
Comparative genomics analysis in Prunoideae to identify biologically relevant polymorphisms.
Plant Biotechnol. J.
PUBLISHED: 03-27-2013
Show Abstract
Hide Abstract
Prunus is an economically important genus with a wide range of physiological and biological variability. Using the peach genome as a reference, sequencing reads from four almond accessions and one sweet cherry cultivar were used for comparative analysis of these three Prunus species. Reference mapping enabled the identification of many biological relevant polymorphisms within the individuals. Examining the depth of the polymorphisms and the overall scaffold coverage, we identified many potentially interesting regions including hundreds of small scaffolds with no coverage from any individual. Non-sense mutations account for about 70 000 of the 13 million identified single nucleotide polymorphisms (SNPs). Blast2GO analyses on these non-sense SNPs revealed several interesting results. First, non-sense SNPs were not evenly distributed across all gene ontology terms. Specifically, in comparison with peach, sweet cherry is found to have non-sense SNPs in two 1-aminocyclopropane-1-carboxylate synthase (ACS) genes and two 1-aminocyclopropane-1-carboxylate oxidase (ACO) genes. These polymorphisms may be at the root of the nonclimacteric ripening of sweet cherry. A set of candidate genes associated with bitterness in almond were identified by comparing sweet and bitter almond sequences. To the best of our knowledge, this is the first report in plants of non-sense SNP abundance in a genus being linked to specific GO terms.
Related JoVE Video
Donepezil treatment stabilizes functional connectivity during resting state and brain activity during memory encoding in Alzheimers disease.
J Clin Psychopharmacol
PUBLISHED: 02-21-2013
Show Abstract
Hide Abstract
Previous studies with functional magnetic resonance imaging (fMRI) demonstrated a differential brain activity and connectivity after treatment with donepezil in Alzheimers disease (AD) when compared to healthy elders. Importantly however, there are no available studies where the placebo or control group included comparable AD patients relative to the treated groups. Fifteen patients recently diagnosed of AD were randomized to treatment (n = 8) or to control group (n = 7); the former receiving daily treatment of donepezil during 3 months. At baseline and follow-up, both groups underwent resting-state as well as task-fMRI examinations, this latter assessing encoding of visual scenes. The treated group showed higher connectivity in areas of the default mode network, namely the right parahippocampal gyrus at follow-up resting-fMRI as compared to the control group. On the other hand, for the task-fMRI, the untreated AD group presented progressive increased activation in the left middle temporal gyrus and bilateral precuneus at the 3-month examination compared to baseline, whereas the treated group exhibited stable patterns of brain activity. Donepezil treatment is associated with stabilization of connectivity of medial temporal regions during resting state and of brain efficiency during a cognitive demand, on the whole reducing progressive dysfunctional reorganizations observed during the natural course of the disease.
Related JoVE Video
Occurrence and behavior of pesticides in wastewater treatment plants and their environmental impact.
Sci. Total Environ.
PUBLISHED: 02-12-2013
Show Abstract
Hide Abstract
Reports on pesticides elimination during wastewater treatment are rare since these substances are typically considered of agricultural rather than of urban origin. In this context, the aim of this work was to evaluate the presence, removal and environmental relevance of 22 selected pesticides in three different wastewater treatment plants (WWTPs), paying attention not only to their occurrence and elimination but also to the toxicity of each pesticide against three aquatic micro organisms (algae, daphnia and fish) through the calculation of the so-named Environmental Relevance of Pesticides from Wastewater treatment plants Index (ERPWI). For this purpose, an analytical method based on isotope dilution on-line solid phase extraction-liquid chromatography-tandem mass spectrometry (SPE-LC-MS/MS) was optimized, allowing the determination of the 22 target pesticides in wastewater with satisfactory sensitivity (limits of detection below 30 ng/L), accuracy and precision. Concerning the results, total pesticide levels were in most instances below 1 ?g/L but removal in the WWTPs was variable and often poor, with concentrations in the effluent sometimes higher than in the corresponding influent. Possible explanations for these poor or negative removal rates are, among many others considered (e.g. sampling, sample preservation, method biases, atmospheric deposition), deconjugation of metabolites and/or transformation products of the pesticides, hydrolysis, and desorption from particulate matter during wastewater treatment. The most significant pesticides in terms of concentration and frequency of detection were diazinon and diuron. These two pesticides, followed by atrazine, simazine and malathion, were also the most relevant from the environmental point of view, according to the calculated ERPWI.
Related JoVE Video
Comparison of plantar pressures and contact area between normal and cavus foot.
Gait Posture
PUBLISHED: 02-04-2013
Show Abstract
Hide Abstract
In pes cavus, the medial longitudinal arch elevation reduces the contact surface area and consequently increases the corresponding plantar pressure measurements. This poor distribution of loads may produce associated pathology and pain in this or other areas of the body. Normal reference values need to be established in order to determine which patterns are prone to pathology.
Related JoVE Video
[Is the morbid obesity surgery profitable in times of crisis? A cost-benefit analysis of bariatric surgery].
Cir Esp
PUBLISHED: 02-03-2013
Show Abstract
Hide Abstract
Morbid obesity is a serious health problem whose prevalence is increasing. Expensive co-morbidities are associated to these patients, as well as a reduction in the survival. Bariatric surgery resolves the co-morbidities (type 2 diabetes mellitus, 86.6%; cardiovascular risk, 79.0%; obstructive sleep apnea syndrome, 83.6%; hypertension, 61.7%), reduces the mortality rate (among 31-40%), and increases the morbid obese patients survival over a 10-years period. It provides significant savings for the National Health System. The obese patients consume a 20% plus of health resources and 68% plus of drugs than general population. Bariatric surgery requires an initial investment (diagnosis-related group cost: 7,468 €), but it is recovered in a cost-effectiveness ratio of 2.5 years. Significant savings are obtained from the third year. To the direct economic benefits associated with reduced health expenditures it should be added an increase in tax collection (sick leave and unemployment reduction is estimated in 18%, with a productivity increase of 57% for self-employed people). Bariatric surgery is one of the most cost-effective procedures in the healthcare system.
Related JoVE Video
A preliminary study of the whole-genome expression profile of sporadic and monogenic early-onset Alzheimers disease.
Neurobiol. Aging
PUBLISHED: 01-28-2013
Show Abstract
Hide Abstract
Alzheimers disease (AD) is the most common neurodegenerative dementia. Approximately 10% of cases present at an age of onset before 65 years old, which in turn can be monogenic familial AD (FAD) or sporadic early-onset AD (sEOAD). Mutations in PSEN1, PSEN2, and APP genes have been linked with FAD. The aim of our study is to describe the brain whole-genome RNA expression profile of the posterior cingulate area in sEOAD and FAD caused by PSEN1 mutations (FAD-PSEN1). Fourteen patients (7 sEOAD and 7 FAD-PSEN1) and 7 neurologically healthy control subjects were selected and whole-genome expression was measured using Affymetrix Human Gene 1.1 microarrays. We identified statistically significant expression changes in sEOAD and FAD-PSEN1 brains with respect to control subjects (3183 and 3350 differentially expressed genes [DEG] respectively, false discovery rate-corrected p < 0.05). Of them, 1916 DEG were common between the 2 comparisons. We did not identify DEG between sEOAD and FAD-PSEN1. Microarray data were validated through real-time quantitative polymerase chain reaction. In silico analysis of DEG revealed an alteration in biological pathways related to intracellular signaling pathways (particularly calcium signaling), neuroactive ligand-receptor interactions, axon guidance, and long-term potentiation in both groups of patients. In conclusion, the altered biological final pathways in sEOAD and FAD-PSEN1 are mainly related with cell signaling cascades, synaptic plasticity, and learning and memory processes. We hypothesize that these 2 groups of early-onset AD with distinct etiologies and likely different could present a neurodegenerative process with potential different pathways that might converge in a common and similar final stage of the disease.
Related JoVE Video
Activation of mammalian target of rapamycin (mTOR) in triple negative feline mammary carcinomas.
BMC Vet. Res.
PUBLISHED: 01-10-2013
Show Abstract
Hide Abstract
Triple negative breast cancer (TNBC) in humans is defined by the absence of oestrogen receptor (ER), progesterone receptor (PR) and HER2 overexpression. Mammalian target of rapamycin (mTOR) is overexpressed in TNBC and it represents a potential target for the treatment of this aggressive tumour. Feline mammary carcinoma (FMC) is considered to be a model for hormone-independent human breast cancer. This study investigated mTOR and p-mTOR expression in FMC in relation to triple negative (TN) phenotype.
Related JoVE Video
Low cerebrospinal fluid concentration of mitochondrial DNA in preclinical Alzheimer disease.
Ann. Neurol.
PUBLISHED: 01-09-2013
Show Abstract
Hide Abstract
To identify a novel biochemical marker that precedes clinical symptoms in Alzheimer disease (AD).
Related JoVE Video
A pan-European study of the C9orf72 repeat associated with FTLD: geographic prevalence, genomic instability, and intermediate repeats.
Julie van der Zee, Ilse Gijselinck, Lubina Dillen, Tim Van Langenhove, Jessie Theuns, Sebastiaan Engelborghs, Stéphanie Philtjens, Mathieu Vandenbulcke, Kristel Sleegers, Anne Sieben, Veerle Bäumer, Githa Maes, Ellen Corsmit, Barbara Borroni, Alessandro Padovani, Silvana Archetti, Robert Perneczky, Janine Diehl-Schmid, Alexandre de Mendonça, Gábriel Miltenberger-Miltényi, Sónia Pereira, José Pimentel, Benedetta Nacmias, Silvia Bagnoli, Sandro Sorbi, Caroline Graff, Huei-Hsin Chiang, Marie Westerlund, Raquel Sánchez-Valle, Albert Lladó, Ellen Gelpi, Isabel Santana, Maria Rosário Almeida, Beatriz Santiago, Giovanni Frisoni, Orazio Zanetti, Cristian Bonvicini, Matthis Synofzik, Walter Maetzler, Jennifer Müller vom Hagen, Ludger Schöls, Michael T Heneka, Frank Jessen, Radoslav Matej, Eva Parobkova, Gabor G Kovacs, Thomas Strobel, Stayko Sarafov, Ivailo Tournev, Albena Jordanova, Adrian Danek, Thomas Arzberger, Gian Maria Fabrizi, Silvia Testi, Eric Salmon, Patrick Santens, Jean-Jacques Martin, Patrick Cras, Rik Vandenberghe, Peter Paul De Deyn, Marc Cruts, Christine Van Broeckhoven, Peter P De Deyn, Jennifer Müller Vom Hagen, Alfredo Ramírez, Delia Kurzwelly, Carmen Sachtleben, Wolfgang Mairer, Clara Firmo, Anna Antonell, Jose Molinuevo, Anne Kinhult Ståhlbom, Håkan Thonberg, Inger Nennesmo, Anne Börjesson-Hanson, Valentina Bessi, Irene Piaceri, Maria Helena Ribeiro, Maria Rosário Almeida, Catarina Oliveira, João Massano, Carolina Garret, Paula Pires, Adrian Danel, Gian Maria Fabrizi, Sergio Ferrari, Tiziana Cavallaro, .
Hum. Mutat.
PUBLISHED: 01-04-2013
Show Abstract
Hide Abstract
We assessed the geographical distribution of C9orf72 G(4) C(2) expansions in a pan-European frontotemporal lobar degeneration (FTLD) cohort (n = 1,205), ascertained by the European Early-Onset Dementia (EOD) consortium. Next, we performed a meta-analysis of our data and that of other European studies, together 2,668 patients from 15 Western European countries. The frequency of the C9orf72 expansions in Western Europe was 9.98% in overall FTLD, with 18.52% in familial, and 6.26% in sporadic FTLD patients. Outliers were Finland and Sweden with overall frequencies of respectively 29.33% and 20.73%, but also Spain with 25.49%. In contrast, prevalence in Germany was limited to 4.82%. In addition, we studied the role of intermediate repeats (7-24 repeat units), which are strongly correlated with the risk haplotype, on disease and C9orf72 expression. In vitro reporter gene expression studies demonstrated significantly decreased transcriptional activity of C9orf72 with increasing number of normal repeat units, indicating that intermediate repeats might act as predisposing alleles and in favor of the loss-of-function disease mechanism. Further, we observed a significantly increased frequency of short indels in the GC-rich low complexity sequence adjacent to the G(4) C(2) repeat in C9orf72 expansion carriers (P < 0.001) with the most common indel creating one long contiguous imperfect G(4) C(2) repeat, which is likely more prone to replication slippage and pathological expansion.
Related JoVE Video
Rare variants in calcium homeostasis modulator 1 (CALHM1) found in early onset Alzheimers disease patients alter calcium homeostasis.
PLoS ONE
PUBLISHED: 01-01-2013
Show Abstract
Hide Abstract
Calcium signaling in the brain is fundamental to the learning and memory process and there is evidence to suggest that its dysfunction is involved in the pathological pathways underlying Alzheimers disease (AD). Recently, the calcium hypothesis of AD has received support with the identification of the non-selective Ca(2+)-permeable channel CALHM1. A genetic polymorphism (p. P86L) in CALHM1 reduces plasma membrane Ca(2+) permeability and is associated with an earlier age-at-onset of AD. To investigate the role of CALHM1 variants in early-onset AD (EOAD), we sequenced all CALHM1 coding regions in three independent series comprising 284 EOAD patients and 326 controls. Two missense mutations in patients (p.G330D and p.R154H) and one (p.A213T) in a control individual were identified. Calcium imaging analyses revealed that while the mutation found in a control (p.A213T) behaved as wild-type CALHM1 (CALHM1-WT), a complete abolishment of the Ca(2+) influx was associated with the mutations found in EOAD patients (p.G330D and p.R154H). Notably, the previously reported p. P86L mutation was associated with an intermediate Ca(2+) influx between the CALHM1-WT and the p.G330D and p.R154H mutations. Since neither expression of wild-type nor mutant CALHM1 affected amyloid ß-peptide (Aß) production or Aß-mediated cellular toxicity, we conclude that rare genetic variants in CALHM1 lead to Ca(2+) dysregulation and may contribute to the risk of EOAD through a mechanism independent from the classical Aß cascade.
Related JoVE Video
Translation, cultural adaptation and validation of a Spanish version of the Irritable Bowel Syndrome Severity Score.
Rev Esp Enferm Dig
PUBLISHED: 11-30-2011
Show Abstract
Hide Abstract
the Irritable Bowel Syndrome Severity Score (IBSSS) is a questionnaire only available in English that classifies IBS patients according to the severity of their symptoms and can be used to guide and monitor the treatment.Aims: to adapt and validate into Spanish the English version of the IBSSS questionnaire.
Related JoVE Video
SYNTAX score reproducibility and variability between interventional cardiologists, core laboratory technicians, and quantitative coronary measurements.
Circ Cardiovasc Interv
PUBLISHED: 10-25-2011
Show Abstract
Hide Abstract
In the Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery (SYNTAX) trial, the SYNTAX score was useful in risk stratifying patients with complex coronary artery disease. The reproducibility of this score may affect its clinical utility. We therefore assessed SYNTAX score interobserver and intraobserver variability among a group of interventional cardiologists (ICs) and an experienced group of angiographic core laboratory (ACL) technicians.
Related JoVE Video
The rotational spectra, potential function, Born-Oppenheimer breakdown, and hyperfine structure of GeSe and GeTe.
J Chem Phys
PUBLISHED: 09-08-2011
Show Abstract
Hide Abstract
The pure rotational spectra of 18 and 21 isotopic species of GeSe and GeTe have been measured in the frequency range 5-24 GHz using a Fabry-Pe?rot-type resonator pulsed-jet Fourier-transform microwave spectrometer. Gaseous samples of both chalcogenides were prepared by a combined dc discharge/laser ablation technique and stabilized in supersonic jets of Ne. Global multi-isotopologue analyses of the derived rotational data, together with literature high-resolution infrared data, produced very precise Dunham parameters, as well as rotational constant Born-Oppenheimer breakdown (BOB) coefficients (?(01)) for Ge, Se, and Te. A direct fit of the same datasets to an appropriate radial Hamiltonian yielded analytic potential-energy functions and BOB radial functions for the X(1)?(+) electronic state of both GeSe and GeTe. Additionally, the electric quadrupole and magnetic hyperfine interactions produced by the nuclei (73)Ge, (77)Se, and (125)Te were observed, yielding much improved quadrupole coupling constants and first determinations of the spin-rotation parameters.
Related JoVE Video
Abnormal accumulation of autophagic vesicles correlates with axonal and synaptic pathology in young Alzheimers mice hippocampus.
Acta Neuropathol.
PUBLISHED: 07-22-2011
Show Abstract
Hide Abstract
Dystrophic neurites associated with amyloid plaques precede neuronal death and manifest early in Alzheimers disease (AD). In this work we have characterized the plaque-associated neuritic pathology in the hippocampus of young (4- to 6-month-old) PS1(M146L)/APP(751SL) mice model, as the initial degenerative process underlying functional disturbance prior to neuronal loss. Neuritic plaques accounted for almost all fibrillar deposits and an axonal origin of the dystrophies was demonstrated. The early induction of autophagy pathology was evidenced by increased protein levels of the autophagosome marker LC3 that was localized in the axonal dystrophies, and by electron microscopic identification of numerous autophagic vesicles filling and causing the axonal swellings. Early neuritic cytoskeletal defects determined by the presence of phosphorylated tau (AT8-positive) and actin-cofilin rods along with decreased levels of kinesin-1 and dynein motor proteins could be responsible for this extensive vesicle accumulation within dystrophic neurites. Although microsomal A? oligomers were identified, the presence of A11-immunopositive A? plaques also suggested a direct role of plaque-associated A? oligomers in defective axonal transport and disease progression. Most importantly, presynaptic terminals morphologically disrupted by abnormal autophagic vesicle buildup were identified ultrastructurally and further supported by synaptosome isolation. Finally, these early abnormalities in axonal and presynaptic structures might represent the morphological substrate of hippocampal dysfunction preceding synaptic and neuronal loss and could significantly contribute to AD pathology in the preclinical stages.
Related JoVE Video
Identifying earlier Alzheimers disease: insights from the preclinical and prodromal phases.
Neurodegener Dis
PUBLISHED: 06-22-2011
Show Abstract
Hide Abstract
Alzheimers disease (AD) has been traditionally conceptualized as a clinicopathological entity, its definite diagnosis requiring the presence of characteristic pathology together with a dementia clinical picture. The fact that certain AD biomarkers show an acceptable sensitivity and specificity to detect AD pathology has shifted the diagnostic paradigm towards a clinicobiological approach. The objective of this paper is to present recent data that show how cerebrospinal fluid (CSF) biomarkers behave in preclinical AD. These studies have been performed in presymptomatic subjects (PreS) and asymptomatic subjects at risk for the disease (AsymR). In brief, the results show in PreS subjects that CSF biomarkers present a positive correlation with time to disease onset to reach floor levels at symptom onset. In addition, memory performance presents distinct associations in the AD continuum, being related to A?(1-42) levels in AsymR subjects and to t-tau and p-tau in prodromal AD. Furthermore, an increase in cortical thickness of typical AD areas was observed when mean A?(1-42) levels were still within the normal range in PreS subjects, or they presented transitional values in AsymR subjects. Overall, these findings suggest that the preclinical stage is biologically active and that there may be structural changes when amyloid is starting its deposition.
Related JoVE Video
"Preclinical" MSA in definite Creutzfeldt-Jakob disease.
Neuropathology
PUBLISHED: 06-21-2011
Show Abstract
Hide Abstract
Multiple system atrophy (MSA) is a sporadic alpha-synucleinopathy clinically characterized by variable degrees of parkinsonism, cerebellar ataxia and autonomic dysfunction. The histopathological hallmark of MSA is glial cytoplasmic inclusion (GCI). It is considered to represent the earliest stage of the degenerative process in MSA and to precede neuronal degeneration. Sporadic Creutzfeldt-Jakob disease (sCJD) is a fatal, rapidly progressive dementia generally associated with ataxia, pyramidal and extrapyramidal symptoms and myoclonus. Definite diagnosis needs neuropathological demonstration of variable degrees of spongiform degeneration of neuropil, neuronal loss, astro- and microgliosis, and the presence of abnormal deposits of the misfolded prion protein PrP(res) . Both diseases, CJD and MSA are infrequent among neurodegenerative diseases. In the present report we describe clinical and neuropathological findings of a previously healthy 64-year-old woman who developed symptoms of classical CJD. At post mortem examination, the brain showed in addition to classical methionine/methionine PrP(res) type 1 (MM1) sCJD changes and moderate Alzheimer-type pathology, features of "preclinical" MSA with minimal histopathological changes. These were characterized by discrete amounts of alpha-synuclein immunoreacive glial cytoplasmic inclusions in the striato-nigral system, isolated intraneuronal inclusions in pigmented neurons of the substantia nigra, as well as some vermiform intranuclear inclusions. To our knowledge, this is the first report on the coexistence of definite sCJD and "minimal changes" MSA in the same patient.
Related JoVE Video
Atypical creutzfeldt-jakob disease evolution after electroconvulsive therapy for catatonic depression.
Case Rep Psychiatry
PUBLISHED: 05-24-2011
Show Abstract
Hide Abstract
We describe a case report of an 80-year-old woman who presented with symptomatology compatible with an episode of major depression with catatonia. After psychiatric admission, electroconvulsive therapy (ECT) was applied, but symptoms progressed with cognitive impairment, bradykinesia, widespread stiffness, postural tremor, and gait disturbance. After compatible magnetic resonance imaging (MRI), diffusion changes, and electroencephalogram (EEG) findings the case was reoriented to Creutzfeldt-Jakob disease (CJD). The genetic study found a methionine/valine heterozygosity at codon 129 of the prion protein gene PrP(Sc). On followup, a significant clinical recovery turned out. For this reason, EEG and MRI were repeated and confirmed the findings. The patient subsequently demonstrated progressive clinical deterioration and died 21 months later. The diagnosis was verified postmortem by neuropathology. The vCJD subtype MV2 is indeed characterized by early and prominent psychiatric symptoms and a prolonged disease duration however no frank clinical recovery has before been reported.
Related JoVE Video
Association between cerebrospinal fluid tau and brain atrophy is not related to clinical severity in the Alzheimers disease continuum.
Psychiatry Res
PUBLISHED: 05-04-2011
Show Abstract
Hide Abstract
We aimed to assess the association between core cerebrospinal fluid (CSF) biomarkers, regional brain atrophy and clinical severity in the Alzheimers disease (AD) continuum, as well as to investigate how cognitive reserve (CR) may modulate these putative associations. Forty-nine subjects (11 controls, 10 patients with subjective memory complaints, 19 with mild cognitive impairment and 9 mild AD) underwent lumbar puncture and high-resolution magnetic resonance imaging (MRI). CSF amyloid-?(1-42) (A?(1-42)), total tau (t-tau) and phosphorylated tau (p-tau(181)) were determined. Voxel-based morphometry (VBM) was applied and multiple regression analyses for the whole sample were carried out. Clinical severity was adjusted using the Clinical Dementia Rating Sum of Boxes score (CDR-SB). A negative correlation between t-tau levels and grey matter (GM) volume in temporo-parietal regions was found, regardless of CDR-SB score. In contrast, the negative correlation between p-tau(181) and GM volume was largely explained by clinical severity, except in the posterior cingulate cortex. CR did not significantly modify these correlations. A?(1-42) levels were not related to GM volume but were related to clinical severity, an association that was attenuated when CR was considered. In conclusion, the present findings reflect that t-tau CSF concentrations are associated with GM atrophy in neuropathologically relevant areas across the AD continuum, whereas the p-tau(181) association is largely dependent on the degree of clinical severity. The relationship between CSF A?(1-42) and clinical severity seems to be modulated by CR, suggesting that there may be subjects with pathological levels of A?(1-42) and high CR estimates who remain clinically asymptomatic.
Related JoVE Video
Age-dependent accumulation of soluble amyloid beta (Abeta) oligomers reverses the neuroprotective effect of soluble amyloid precursor protein-alpha (sAPP(alpha)) by modulating phosphatidylinositol 3-kinase (PI3K)/Akt-GSK-3beta pathway in Alzheimer mouse m
J. Biol. Chem.
PUBLISHED: 04-01-2011
Show Abstract
Hide Abstract
Neurotrophins, activating the PI3K/Akt signaling pathway, control neuronal survival and plasticity. Alterations in NGF, BDNF, IGF-1, or insulin signaling are implicated in the pathogenesis of Alzheimer disease. We have previously characterized a bigenic PS1×APP transgenic mouse displaying early hippocampal A? deposition (3 to 4 months) but late (17 to 18 months) neurodegeneration of pyramidal cells, paralleled to the accumulation of soluble A? oligomers. We hypothesized that PI3K/Akt/GSK-3? signaling pathway could be involved in this apparent age-dependent neuroprotective/neurodegenerative status. In fact, our data demonstrated that, as compared with age-matched nontransgenic controls, the Ser-9 phosphorylation of GSK-3? was increased in the 6-month PS1×APP hippocampus, whereas in aged PS1×APP animals (18 months), GSK-3? phosphorylation levels displayed a marked decrease. Using N2a and primary neuronal cell cultures, we demonstrated that soluble amyloid precursor protein-? (sAPP?), the predominant APP-derived fragment in young PS1×APP mice, acting through IGF-1 and/or insulin receptors, activated the PI3K/Akt pathway, phosphorylated the GSK-3? activity, and in consequence, exerted a neuroprotective action. On the contrary, several oligomeric A? forms, present in the soluble fractions of aged PS1×APP mice, inhibited the induced phosphorylation of Akt/GSK-3? and decreased the neuronal survival. Furthermore, synthetic A? oligomers blocked the effect mediated by different neurotrophins (NGF, BDNF, insulin, and IGF-1) and sAPP?, displaying high selectivity for NGF. In conclusion, the age-dependent appearance of APP-derived soluble factors modulated the PI3K/Akt/GSK-3? signaling pathway through the major neurotrophin receptors. sAPP? stimulated and A? oligomers blocked the prosurvival signaling. Our data might provide insights into the selective vulnerability of specific neuronal groups in Alzheimer disease.
Related JoVE Video
[Assessment of degree of psychological health involvement in pre-laryngectomized patients].
Acta Otorrinolaringol Esp
PUBLISHED: 02-25-2011
Show Abstract
Hide Abstract
Several authors have found increased anxiety in patients the day before an intervention and its correlation with anxiety levels the post-operative period. In this study, we determined a number of problems to which patients who underwent total laryngectomy often objected: the tracheostomy, being left without a voice and it being an aggressive, major surgery. Our objective was to assess the degree of anxiety and fears of the patient prior to total laryngectomy.
Related JoVE Video
Monitoring of (bio)available labile metal fraction in a drinking water treatment plant by diffusive gradients in thin films.
Environ Monit Assess
PUBLISHED: 02-23-2011
Show Abstract
Hide Abstract
A performance study of diffusive gradients in thin films (DGT) and inductively coupled plasma optical emission spectrometry (ICP-OES) was applied for the monitoring of the labile fraction of metals Al, Cd, Co, Cr, Cu, Fe, Mn, Ni, Pb and Zn, in Sant Joan Despí Drinking Water Treatment Plant located in the South of Barcelonas Metropolitan Area (Spain). The DWTP monitoring protocol was optimized by working for 1 day of deployment (24 h) with the DGT device in contact with both treated and river water matrixes. Additionally, it was demonstrated that an increase in the deployment time of 1 week did not decrease the evaluated concentrations of the studied metals. The quality parameters of the DGT device and ICP-OES determination, such as limit of quantification, accuracy expressed as relative error (%) and reproducibility expressed as relative standard deviation, were evaluated. Good results were obtained for all the metals in ultrapure water; limits of quantification ranged from 1.5 ?g L(?-?1) for cadmium to 28 ?g L(?-?1) for zinc when deployment time of 24 h was used and from 0.2 ?g L(?-?1) for cadmium to 4 ?g L(?-?1) for zinc when this time was increased by 1 week. Accuracy and precisions lower than or equal to 10% were obtained at a parametric concentration value of the metals regulated in the European Drinking Water Guidelines (98/83/EC). DGT deployment was tested in river and treated water, and good results were obtained for Cd, Ni, Co and Zn, whereas for the other metals, a continuous control of their metallic labile fractions was monitored. Therefore, DGT device allows the continuous monitoring of the labile metal species in a drinking water treatment plant.
Related JoVE Video
Cognitively preserved subjects with transitional cerebrospinal fluid ß-amyloid 1-42 values have thicker cortex in Alzheimers disease vulnerable areas.
Biol. Psychiatry
PUBLISHED: 02-15-2011
Show Abstract
Hide Abstract
Establishing the relationship between cerebrospinal fluid (CSF) ß-amyloid 1-42 (Aß) and cortical thickness (CTh) would represent a major step forward in the understanding of the Alzheimers disease (AD) process. We studied this relationship in a group of healthy control subjects and subjects with subjective memory complaints with preserved cognitive function at neuropsychological testing.
Related JoVE Video
Dynamic plantar pressure analysis and midterm outcomes in percutaneous correction for mild hallux valgus.
J. Orthop. Res.
PUBLISHED: 02-05-2011
Show Abstract
Hide Abstract
Mild hallux valgus (HV), which can lead to alteration of the plantar pressure pattern with an overpressure under the hallux, can be repaired percutaneously. Our goals were to determine whether the percutaneous distal soft tissue release (DSTR)-Akin procedure restores the loading pattern and to evaluate which are the determinants of the measures of post-operative outcome. Seventy-nine percutaneous DSTR-Akin procedures were performed in the same number of patients. The plantar pressure patterns were evaluated using the BioFoot/IBV® in-shoe system and compared with measurements from 98 controls. The clinical and radiological outcome parameters measured were the pre- and post-operative AOFAS scores, and the first intermetatarsal, hallux abductus, and first metatarsal-hallux declination angles (FIMA, HAA, FMHDA) in weight-bearing radiographs. The mean follow-up was 28.1 (range 24-33) months. The plantar pressure analysis showed a significant decrease (328-152?kPa, p?=?0.001) in the mean pressure under the hallux. Significant improvements occurred in the AOFAS scores, and angular deviations were reduced. The post-operative HAA correlated with the mean pressure under the 1st toe (r(2) ?=?0.132, p?
Related JoVE Video
A novel PSEN1 gene mutation (L235R) associated with familial early-onset Alzheimers disease.
Neurosci. Lett.
PUBLISHED: 01-18-2011
Show Abstract
Hide Abstract
Mutations in the presenilin 1 (PSEN1) gene are the most frequent cause of familial Alzheimers disease (AD), with at least 182 different mutations published to date. We report a 48-year-old woman (age at onset 47 years) who presented a progressive alteration of episodic memory, spatial disorientation, apathy, language disturbances and neglect of personal care. Her MMSE score was 20/30. The patient presented an unusually rapid deterioration and at 6 months follow-up her cognitive and functional status had worsened considerably (MMSE score of 11). Cranial MRI showed a bilateral atrophy with temporal and parietal predominance and the quantification of AD CSF biomarkers showed the typical AD signature. Family history evidenced an autosomal dominant pattern of inheritance. Mutational screening was performed by direct sequencing of exons 3-12 of PSEN1. The patient presented the 3/3 APOE genotype. Genetic analysis revealed a nucleotide substitution in exon 7 of PSEN1 gene, producing a missense mutation in codon 235 from leucine amino acid to arginine (L235R). This amino acid is conserved between presenilin-1 and presenilin-2 proteins. The L235R mutation had not been previously reported, although other mutations in the same residue have also been associated with familial early-onset AD, providing support for the importance of this residue for the presenilin-1 function.
Related JoVE Video
Prognostic value of the SYNTAX score in patients with acute coronary syndromes undergoing percutaneous coronary intervention: analysis from the ACUITY (Acute Catheterization and Urgent Intervention Triage StrategY) trial.
J. Am. Coll. Cardiol.
PUBLISHED: 01-06-2011
Show Abstract
Hide Abstract
We sought to investigate the predictive value of the SYNTAX (Synergy Between PCI With Taxus and Cardiac Surgery) score (SS) for risk assessment of 1-year clinical outcomes in patients with non-ST-segment elevation acute coronary syndromes undergoing percutaneous coronary intervention (PCI).
Related JoVE Video
Juvenile neuronal ceroid lipofuscinosis: clinical course and genetic studies in Spanish patients.
J. Inherit. Metab. Dis.
PUBLISHED: 01-06-2011
Show Abstract
Hide Abstract
Juvenile neuronal ceroid lipofuscinosis (JNCL, NCL3, Batten disease) is usually caused by a 1.02-kb deletion in the CLN3 gene. Mutations in the CLN1 gene may be associated with a variant form of JNCL (vJNCL). We report the clinical course and molecular studies in 24 patients with JNCL collected from 1975 to 2010 with the aim of assessing the natural history of the disorder and phenotype/genotype correlations.
Related JoVE Video
Cerebrospinal fluid biomarkers in Alzheimers disease families with PSEN1 mutations.
Neurodegener Dis
PUBLISHED: 01-05-2011
Show Abstract
Hide Abstract
Familial Alzheimers disease allows studies in the preclinical phases of the disease. We studied cerebrospinal fluid (CSF) amyloid ?1-42 (A?1-42), total tau (t-tau) and phospho-tau181 (p-tau) levels in PSEN1 families and correlated the results with the genetic status, age and clinical stage.
Related JoVE Video
Applying the new research diagnostic criteria: MRI findings and neuropsychological correlations of prodromal AD.
Int J Geriatr Psychiatry
PUBLISHED: 01-04-2011
Show Abstract
Hide Abstract
We describe the neuroimaging characteristics of prodromal AD (PrdAD) patients diagnosed using the new research criteria in a clinical setting. In order to further characterize these patients, we also study the relationship between neuropsychology, CSF biomarkers and magnetic resonance imaging (MRI) findings.
Related JoVE Video
Psychometric properties of the Social Phobia and Anxiety Inventory for Children in a Spanish sample.
Span J Psychol
PUBLISHED: 10-28-2010
Show Abstract
Hide Abstract
The objectives of the present study were to adapt and analyze the factor structure, reliability, and validity of the Social Phobia and Anxiety Inventory for Children (SPAI-C; Beidel, Turner, & Morris, 1995) in a Spanish population. The SPAI-C was applied to a sample of 1588 children and adolescents with ages ranging from 10 to 17 years. The confirmatory factor analysis (CFA) showed a four-factor structure: Public performance, Assertiveness, Fear and avoidance/escape in social encounters, and Cognitive and psychophysiological interferences. Internal consistency was high (.90) and test-retest reliability was moderate (.56). Significant differences were found in the variables sex and age, although the effect size was small in both variables and their interaction. Overall, the increase of the age value was inversely proportional to that of social anxiety measured with the SPAI-C; in participants of the same age, values were higher for girls than for boys. Results suggest that the Social Phobia and Anxiety Inventory For Children is a valid and reliable instrument to assess social anxiety in Spanish children and adolescents.
Related JoVE Video
Different profiles of Alzheimers disease cerebrospinal fluid biomarkers in controls and subjects with subjective memory complaints.
J Neural Transm
PUBLISHED: 08-20-2010
Show Abstract
Hide Abstract
Cerebrospinal fluid (CSF) biomarkers, such as A?(42), total-tau and phosphorylated-tau(181) reflect neuropathological changes of Alzheimers disease (AD). We studied these biomarkers in 24 controls and 19 subjects with subjective memory complaints, and we distinguished different CSF profiles: normal (group 1, 55.8%), only pathologic A?(42) (group 2, 27.9%), pathologic A?(42) plus pathologic total-tau and/or phosphorylated-tau(181) (group 3, 7%), and only pathologic total-tau and phosphorylated-tau(181) (group 4, 9.3%). Group 2 could represent an earlier phase of preclinical AD than group 3, and group 4 an unknown etiology.
Related JoVE Video
Occurrence, partition and removal of pharmaceuticals in sewage water and sludge during wastewater treatment.
Water Res.
PUBLISHED: 06-30-2010
Show Abstract
Hide Abstract
During 8 sampling campaigns carried out over a period of two years, 72 samples, including influent and effluent wastewater, and sludge samples from three conventional wastewater treatment plants (WWTPs), were analyzed to assess the occurrence and fate of 43 pharmaceutical compounds. The selected pharmaceuticals belong to different therapeutic classes, i.e. non-steroidal anti-inflammatory drugs, lipid modifying agents (fibrates and statins), psychiatric drugs (benzodiazepine derivative drugs and antiepileptics), histamine H2-receptor antagonists, antibacterials for systemic use, beta blocking agents, beta-agonists, diuretics, angiotensin converting enzyme (ACE) inhibitors and anti-diabetics. The obtained results showed the presence of 32 target compounds in wastewater influent and 29 in effluent, in concentrations ranging from low ng/L to a few ?g/L (e.g. NSAIDs). The analysis of sludge samples showed that 21 pharmaceuticals accumulated in sewage sludge from all three WWTPs in concentrations up to 100 ng/g. This indicates that even good removal rates obtained in aqueous phase (i.e. comparison of influent and effluent wastewater concentrations) do not imply degradation to the same extent. For this reason, the overall removal was estimated as a sum of all the losses of a parent compound produces by different mechanisms of chemical and physical transformation, biodegradation and sorption to solid matter. The target compounds showed very different removal rates and no logical pattern in behaviour even if they belong to the same therapeutic groups. What is clear is that the elimination of most of the substances is incomplete and improvements of the wastewater treatment and subsequent treatments of the produced sludge are required to prevent the introduction of these micro-pollutants in the environment.
Related JoVE Video
Neuropsychological profile of prodromal Alzheimers disease (Prd-AD) and their radiological correlates.
Arch Gerontol Geriatr
PUBLISHED: 03-17-2010
Show Abstract
Hide Abstract
This study describes the cognitive profile of Prd-AD, the neuropsychological tests that may predict progression to dementia, and to study their brain structural correlates. We enrolled 24 stable amnesics who did not develop dementia after two years follow-up; 27 patients were considered as Prd-AD, in the initial visit, since they fulfilled NINCDS-ADRDA criteria after two years; 31 Alzheimers disease (AD) patients and 27 controls (CTR). Structural magnetic resonance imaging (MRI), as well as a neuropsychological battery was performed at the initial visit. The key findings were: Prd-AD patients were characterized by prominent episodic memory dysfunction and minimal semantic memory and executive dysfunction. Semantic fluency test (Sem-Flu), delayed text memory test (Del-text-mem) and memory alteration test (M@T) (including both episodic and semantic memory), together with trail making test A (TMT-A), resulted significant predictors for dementia development in this group of amnesic patients. This optimal predictive model obtained an estimated accuracy of 53% after two years follow-up. M@T and semantic Sem-Flu test performance presented high correlation with decreased gray matter density in the left lateral temporal lobe. We conclude that Prd-AD is characterized by prominent episodic memory dysfunction and minimal semantic memory and executive dysfunction which are related with left medial, inferior and lateral temporal density loss, predominantly in the left side.
Related JoVE Video
[Utility of bone replacement material in cochlear implant, skull base and sinus surgery: our experience].
Acta Otorrinolaringol Esp
PUBLISHED: 03-14-2010
Show Abstract
Hide Abstract
To solve certain problems that arise in cochlear implant, sinus and skull base surgery, the use of bone cement (PolyBone®) has been introduced in our department. With the goal of making use of surgical bone cements, combining bone growth factors and polyphosphates has allowed the study of these biological materials.
Related JoVE Video
Immunoneutralization of inhibin in cycling rats increases follicle-stimulating hormone secretion, stimulates the ovary and attenuates progesterone receptor-dependent preovulatory luteinizing hormone secretion.
Neuroendocrinology
PUBLISHED: 03-12-2010
Show Abstract
Hide Abstract
Passive immunization against inhibin with an anti-inhibin serum (AIS) during the diestrous phase in cycling rats increased follicle-stimulating hormone secretion, stimulated the ovaries and reduced the magnitude of the luteinizing hormone (LH) surge in the afternoon of proestrus. The involvement of gonadotrope progesterone receptor (PR) expression/action in the inhibitory effects of the follicle-stimulating hormone-dependent putative ovarian factor gonadotropin surge-attenuating factor on preovulatory LH secretion was studied in the absence of circulating free inhibin. Proestrous pituitaries from rats injected with AIS or a non-immune serum (NIS) were studied for determination of PR-AB and PR-B mRNAs by RT-PCR and PR-B and PR-A isoform proteins by Western blot. In addition, pituitaries from AIS- and NIS-injected rats were incubated and studied for PR-dependent LH secretion parameters: LH-releasing hormone (LHRH)-stimulated LH secretion, progesterone-potentiated LHRH-stimulated LH secretion and LHRH self-priming. Also, the effects of the antiprogestagen RU486 on these LH secretion parameters were evaluated and compared with those of AIS. Finally, gonadotrope PR phosphorylation was evaluated by immunohistochemistry. Results showed that the hyperstimulated ovaries of AIS-injected rats produce a factor, different from inhibin, that blocked LHRH self-priming and P-potentiation of LHRH-stimulated LH secretion. These effects were not due to decreased pituitary PR mRNAs, PR protein expression or PR protein B/A ratio. The inhibitory effect of AIS on PR-dependent LH secretion seemed to be due to gonadotrope PR dephosphorylation. Taken together, the findings indicated that the putative gonadotropin surge-attenuating factor affected LH surge through an inhibition of PR phosphorylation/action but not PR expression.
Related JoVE Video
Identification and characterisation of a Maf1/Macoco protein complex that interacts with GABAA receptors in neurons.
Mol. Cell. Neurosci.
PUBLISHED: 03-09-2010
Show Abstract
Hide Abstract
The majority of fast inhibitory synaptic transmission in the mammalian nervous system is mediated by GABA(A) receptors (GABA(A)Rs). Here we report a novel interaction between the protein Maf1 and GABA(A)R beta-subunit intracellular domains. We find Maf1 to be highly expressed in brain and enriched in the hippocampus and cortex. In heterologous cells and neurons we show Maf1 co-localises with GABA(A)Rs in intracellular compartments and at the cell surface. In neurons, Maf1 is found localised in the cytoplasm in dendrites, partially overlapping with GABA(A)Rs and inhibitory synapses and in addition is enriched in the neuronal nucleus. We also report that Maf1 interacts with a novel coiled-coil domain containing protein that we have called Macoco (for Maf1 interacting coiled-coil protein). Like Maf1, Macoco can also be found localised to inhibitory synapses and directly interacts with GABA(A)Rs. Expressing Macoco in neurons increases surface GABA(A)R levels. Our results suggest that Maf1 and Macoco are novel GABA(A)R interacting proteins important for regulating GABA(A)R surface expression and GABA(A)R signalling in the brain.
Related JoVE Video
Plantar pressures determinants in mild Hallux Valgus.
Gait Posture
PUBLISHED: 03-03-2010
Show Abstract
Hide Abstract
While podobarometric techniques have been applied to the study of pressures in Hallux Valgus (HV), little is known about its clinical and radiological determinants. So, the aim of the present study was to determine the plantar pressure pattern in participants with mild HV, comparing to a control group, and their clinical and anthropometric determinants. Biofoot/IBV(®) in-shoe system was used to evaluate 79 participants with mild HV. Computerized measurements of the 1st intermetatarsal angle (IMA) and the hallux abductus angle (HAA) were made on antero-posterior radiographs. The clinical outcome was assessed using the AOFAS score. The dependent baropodometric variables and the independent clinical and anthropometric variables were subjected to a multiple regression analysis. In both groups, the highest average pressure was in the 2nd metatarsal head (MTH). The mean pressure under the Hallux was significantly higher in HV group (controls, 146.5±92.5kPa; HV, 328.5±113.2kPa; p<0.001). An 18.6% of average pressure under the 1st MTH was accounted for pain, first ray alignment and total AOFAS score. Variations of the HAA explained 26.8% of the mean Hallux pressure. Women with mild HV present with pathologically increased pressure under the Hallux, which is caused by the altered alignment of the first ray. Pain and clinical result were associated with the pressure under the 1st MTH and the remaining variables were only moderate predictors of dynamic plantar pressures.
Related JoVE Video
[Relearning vocabulary. A comparative analysis between a case of dementia and Alzheimers disease with predominant compromise of language].
Rev Neurol
PUBLISHED: 02-11-2010
Show Abstract
Hide Abstract
Semantic dementia is characterised by a progressive loss of semantic content that initially affects the capacity to name things, and is associated with asymmetric atrophy of the anterior temporal lobes. In Alzheimers disease (AD) with predominant compromise of language, anomia is also the main symptom. The study examined the capacity to relearn vocabulary of two patients, each exhibiting one of these two forms of degenerative anomia.
Related JoVE Video
Multiphoton in vivo imaging of amyloid in animal models of Alzheimers disease.
Neuropharmacology
PUBLISHED: 01-07-2010
Show Abstract
Hide Abstract
Amyloid-beta (Abeta) deposition is a defining feature of Alzheimers disease (AD). The toxicity of Abeta aggregation is thought to contribute to clinical deficits including progressive memory loss and cognitive dysfunction. Therefore, Abeta peptide has become the focus of many therapeutic approaches for the treatment of AD due to its central role in the development of neuropathology of AD. In the past decade, taking the advantage of multiphoton microscopy and molecular probes for amyloid peptide labeling, the dynamic progression of Abeta aggregation in amyloid plaques and cerebral amyloid angiopathy has been monitored in real time in transgenic mouse models of AD. Moreover, amyloid plaque-associated alterations in the brain including dendritic and synaptic abnormalities, changes of neuronal and astrocytic calcium homeostasis, microglial activation and recruitment in the plaque location have been extensively studied. These studies provide remarkable insight to understand the pathogenesis and pathogenicity of amyloid plaques in the context of AD. The ability to longitudinally image plaques and related structures facilitates the evaluation of therapeutic approaches targeting toward the clearance of plaques.
Related JoVE Video
Direct interaction of GABAB receptors with M2 muscarinic receptors enhances muscarinic signaling.
J. Neurosci.
PUBLISHED: 12-18-2009
Show Abstract
Hide Abstract
Downregulation of G-protein-coupled receptors (GPCRs) provides an important mechanism for reducing neurotransmitter signaling during sustained stimulation. Chronic stimulation of M(2) muscarinic receptors (M(2)Rs) causes internalization of M(2)R and G-protein-activated inwardly rectifying potassium (GIRK) channels in neuronal PC12 cells, resulting in loss of function. Here, we show that coexpression of GABA(B) R2 receptors (GBR2s) rescues both surface expression and function of M(2)R, including M(2)R-induced activation of GIRKs and inhibition of cAMP production. GBR2 showed significant association with M(2)R at the plasma membrane but not other GPCRs (M(1)R, mu-opioid receptor), as detected by fluorescence resonance energy transfer measured with total internal reflection fluorescence microscopy. Unique regions of the proximal C-terminal domains of GBR2 and M(2)R mediate specific binding between M(2)R and GBR2. In the brain, GBR2, but not GBR1, biochemically coprecipitates with M(2)R and overlaps with M(2)R expression in cortical neurons. This novel heteromeric association between M(2)R and GBR2 provides a possible mechanism for altering muscarinic signaling in the brain and represents a previously unrecognized role for GBR2.
Related JoVE Video
Deficits in spatial memory correlate with modified {gamma}-aminobutyric acid type A receptor tyrosine phosphorylation in the hippocampus.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 11-10-2009
Show Abstract
Hide Abstract
Fast synaptic inhibition in the brain is largely mediated by gamma-aminobutyric acid receptors (GABA(A)R). While the pharmacological manipulation of GABA(A)R function by therapeutic agents, such as benzodiazepines can have profound effects on neuronal excitation and behavior, the endogenous mechanisms neurons use to regulate the efficacy of synaptic inhibition and their impact on behavior remains poorly understood. To address this issue, we created a knock-in mouse in which tyrosine phosphorylation of the GABA(A)Rs gamma2 subunit, a posttranslational modification that is critical for their functional modulation, has been ablated. These animals exhibited enhanced GABA(A)R accumulation at postsynaptic inhibitory synaptic specializations on pyramidal neurons within the CA3 subdomain of the hippocampus, primarily due to aberrant trafficking within the endocytic pathway. This enhanced inhibition correlated with a specific deficit in spatial object recognition, a behavioral paradigm dependent upon CA3. Thus, phospho-dependent regulation of GABA(A)R function involving just two tyrosine residues in the gamma2 subunit provides an input-specific mechanism that not only regulates the efficacy of synaptic inhibition, but has behavioral consequences.
Related JoVE Video
simple hit counter

What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

How does it work?

We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

Video X seems to be unrelated to Abstract Y...

In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.