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Neurobiology of Aging Nov 2015We compared cortical thickness between patients with late-life depression (LLD) and healthy controls and between patients with early-onset (EOD) and late-onset (LOD)...
We compared cortical thickness between patients with late-life depression (LLD) and healthy controls and between patients with early-onset (EOD) and late-onset (LOD) depression. We also tested age effects on cortical thickness in LLD and controls and if cortical thickness and hippocampal volumes were associated with cognitive performance in LLD. Three-dimensional T1-weighted magnetic resonance images were obtained in 49 LLD and 49 matched hospital controls and processed using FreeSurfer. General linear model analysis was used as a statistical approach. LLD group had thinning in the left parahippocampal, fusiform, and inferior-parietal cortex compared with controls. Age correlated with cortical thinning in controls but not in LLD. Women in the LOD groups had extensive cortical thinning in the lateral prefrontal cortex bilaterally compared with EOD women. Absence of statistically significant changes observed in men should however be treated with caution because of the low number of men in the study. Mini-Mental Status Examination score correlated with lateral prefrontal cortical thickness bilaterally and hippocampal volume in the total group of LLD and in LOD but not EOD. LLD is associated with cortical thinning, which is associated with age at depression onset, gender, and level of cognitive functioning.
Topics: Aged; Aged, 80 and over; Aging; Atrophy; Cerebral Cortex; Cognition; Depression; Female; Hippocampus; Humans; Late Onset Disorders; Magnetic Resonance Angiography; Male; Neuropsychological Tests; Organ Size; Prefrontal Cortex
PubMed: 26277679
DOI: 10.1016/j.neurobiolaging.2015.04.020 -
Nature Reviews. Genetics May 2015For many years, linkage analysis was the primary tool used for the genetic mapping of Mendelian and complex traits with familial aggregation. Linkage analysis was... (Review)
Review
For many years, linkage analysis was the primary tool used for the genetic mapping of Mendelian and complex traits with familial aggregation. Linkage analysis was largely supplanted by the wide adoption of genome-wide association studies (GWASs). However, with the recent increased use of whole-genome sequencing (WGS), linkage analysis is again emerging as an important and powerful analysis method for the identification of genes involved in disease aetiology, often in conjunction with WGS filtering approaches. Here, we review the principles of linkage analysis and provide practical guidelines for carrying out linkage studies using WGS data.
Topics: Algorithms; Female; Genetic Linkage; Genome, Human; Genome-Wide Association Study; Genotyping Techniques; Humans; Lod Score; Male; Pedigree; Penetrance; Phenotype; Polymorphism, Single Nucleotide; Sequence Analysis, DNA; Software
PubMed: 25824869
DOI: 10.1038/nrg3908 -
Chemicke Zvesti 2023In this study an efficient and environment friendly electrochemical sensor has been designed for the analysis of acetaminophen (APAP) drug. Electrochemical impedance...
UNLABELLED
In this study an efficient and environment friendly electrochemical sensor has been designed for the analysis of acetaminophen (APAP) drug. Electrochemical impedance spectroscopy, differential pulse voltammetry and cyclic voltammetric techniques were used to demonstrate the fabricated erGO/GCE sensor performance. Voltammetric assessment of acetaminophen drug was done using bare GC electrode, drop-casted GO/GC electrode and erGO/GCE electrochemical sensor. Proposed sensor was precisely validated for APAP detection by differential pulse voltammetric technique. Subsequently LOD, LOQ, sensitivity and linearity were determined and found to be 7.23 nM, 21.909 nM, 20.14 μA nM cm and 0.0219-2.30 μM, respectively. The diffusion coefficient of APAP was determined by chronoamperometry, and it was found to be 2.24 × 10 cm.s. The synthetic and analytical steps were assessed as per the Green Chemistry's 12 Principles giving a 66 score (acceptable) and 93 score (excellent) for the said steps, respectively.
SUPPLEMENTARY INFORMATION
The online version contains supplementary material available at 10.1007/s11696-022-02628-9.
PubMed: 36589858
DOI: 10.1007/s11696-022-02628-9 -
Sensitivity and performance of three novel quantitative assays of SARS-CoV-2 nucleoprotein in blood.Scientific Reports Feb 2023To assess if SARS-CoV-2 (COVID-19) systemic disease can be determined by available nucleoprotein assays, we compared the performance of three commercial SARS-CoV-2...
To assess if SARS-CoV-2 (COVID-19) systemic disease can be determined by available nucleoprotein assays, we compared the performance of three commercial SARS-CoV-2 nucleoprotein (N) assays in plasma. A total of 272 plasma samples collected in the period November-December 2021 were analyzed by the methods Simoa SARS CoV-2 N Protein Advantage Kit [Quanterix Simoa], Solsten SARS-CoV-2 Antigen enzyme immunosorbent assay (ELISA) [Solsten ELISA], and Elecsys SARS-CoV-2 Antigen electrochemiluminescence immunoassay [Elecsys ECLIA]. Additionally, a dilution series of inactivated virus culture was analyzed by the three assays. The SARS CoV-2 PCR-status was not known for the patients. Linear correlation in the pairwise correlation between assays as well as linearity of dilution series of inactivated virus culture was estimated by Spearman score. Sensitivity and specificity were estimated by pairwise comparison. The three assays showed poor agreement on patient samples with regards to concentration. Performance on virus culture was excellent but with different level of detection (LOD). Positive vs negative results show comparable sensitivity and specificity of Quanterix Simoa and Solsten ELISA, with a higher LOD in Elecsys ECLIA and thus lower sensitivity and high specificity. N by all tested assays can be used as a marker for systemic COVID-19 disease.
Topics: Humans; SARS-CoV-2; COVID-19; Plasma; Biological Assay; Immunosorbents; Nucleoproteins
PubMed: 36806155
DOI: 10.1038/s41598-023-29973-3 -
Clinical Genetics Jul 2022Congenital anomalies of the kidney and urinary tract (CAKUT) are a spectrum of abnormalities affecting morphogenesis of the kidneys and other structures of the urinary...
Congenital anomalies of the kidney and urinary tract (CAKUT) are a spectrum of abnormalities affecting morphogenesis of the kidneys and other structures of the urinary tract. Bilateral renal agenesis (BRA) is the most severe presentation of CAKUT. Loss of either nephronectin (NPNT) or its receptor ITGA8 leads to failure of metanephric kidney development with resulting renal agenesis in murine models. Very recently, a single family with renal agenesis and a homozygous truncating variant in NPNT was reported. We report two families in whom genome-wide linkage analysis showed an autozygous locus linked to BRA (at least one member has unilateral renal agenesis) at 4q24, with an LOD score of ~3. Exome sequencing detected a nonsense variant in NPNT in both families within the linkage interval. The pathogenicity of this variant was supported by reverse transcription polymerase chain reaction data showing complete nonsense-mediated decay of the NPNT transcript. Our report confirms the candidacy of NPNT in renal agenesis in humans and shows that even complete loss of function can be compatible with the formation of a single kidney.
Topics: Animals; Congenital Abnormalities; Extracellular Matrix Proteins; Humans; Kidney; Kidney Diseases; Mice; Solitary Kidney; Urogenital Abnormalities; Vesico-Ureteral Reflux
PubMed: 35246978
DOI: 10.1111/cge.14128 -
Brain : a Journal of Neurology Mar 2021Oculopharyngodistal myopathy is a late-onset degenerative muscle disorder characterized by ptosis and weakness of the facial, pharyngeal, and distal limb muscles. A...
Oculopharyngodistal myopathy is a late-onset degenerative muscle disorder characterized by ptosis and weakness of the facial, pharyngeal, and distal limb muscles. A recent report suggested a non-coding trinucleotide repeat expansion in LRP12 to be associated with the disease. Here we report a genetic study in a Chinese cohort of 41 patients with the clinical diagnosis of oculopharyngodistal myopathy (21 cases from seven families and 20 sporadic cases). In a large family with 12 affected individuals, combined haplotype and linkage analysis revealed a maximum two-point logarithm of the odds (LOD) score of 3.3 in chromosomal region chr19p13.11-p13.2 and narrowed the candidate region to an interval of 4.5 Mb. Using a comprehensive strategy combining whole-exome sequencing, long-read sequencing, repeat-primed polymerase chain reaction and GC-rich polymerase chain reaction, we identified an abnormal CGG repeat expansion in the 5' UTR of the GIPC1 gene that co-segregated with disease. Overall, the repeat expansion in GIPC1 was identified in 51.9% independent pedigrees (4/7 families and 10/20 sporadic cases), while the repeat expansion in LRP12 was only identified in one sporadic case (3.7%) in our cohort. The number of CGG repeats was <30 in controls but >60 in affected individuals. There was a slight correlation between repeat size and the age at onset. Both repeat expansion and retraction were observed during transmission but somatic instability was not evident. These results further support that non-coding CGG repeat expansion plays an essential role in the pathogenesis of oculopharyngodistal myopathy.
Topics: 5' Untranslated Regions; Adaptor Proteins, Signal Transducing; Adult; Aged; Aged, 80 and over; Asian People; Female; Humans; Male; Middle Aged; Muscle, Skeletal; Muscular Dystrophies; Mutation; Pedigree; Polymorphism, Single Nucleotide; Trinucleotide Repeat Expansion; Exome Sequencing
PubMed: 33374016
DOI: 10.1093/brain/awaa426 -
Cureus Apr 202390% of visually impaired people live in developing countries. There are various types of vision impairment, but the focus of the current study is retinitis pigmentosa...
INTRODUCTION
90% of visually impaired people live in developing countries. There are various types of vision impairment, but the focus of the current study is retinitis pigmentosa (RP). Up to now, 150 mutations have been reported that are linked with RP.
METHODOLOGY
Healthy and affected members from two Pakistani families (RP01 and RP02) segregating autosomal recessive RP were selected for DNA extraction. PCR was conducted, and the amplified PCR products were analyzed using Polyacrylamide Gel Electrophoresis (PAGE) and visualized in the Gel Doc system for linkage analysis. The Gene Hunter 2.1r5 tool in the Simple Linkage v5.052 beta software suite was used to conduct multipoint parametric linkage analysis on the two consanguineous families examined on the 6K Illumina array. Exons and intron-exon borders of all known arRP genes found in homozygous areas were sequenced in the matching probands using a 3130 automated sequencer and the Big Dye Terminator Cycle Sequencing Kit v3.1. The mutation study was carried out using the AlaMut 1.5 program.
RESULTS
In both families, linkage analysis was performed using microsatellite marker DIS422 for gene and microsatellite marker D8S2332 for gene . Multipoint linkage analysis identifies genomic regions that could potentially contain the genetic defect. In family RP01, only a single peak with a maximal multipoint LOD score of 3.00 was identified on chromosome 1, whereas in family RP02, multiple peaks with multipoint LOD scores of 1.80 were identified on chromosome 8. Analysis of the gene revealed a homozygous substitution of glycine for valine (c.1152T>G; p.V243G), whereas the gene demonstrated that leucine was substituted for proline as a result of cytosine to thymine transfer (c.3419C>T; p. P1035L). Conclusion: Homozygosity mapping is a powerful method for finding genetic abnormalities that are both precise and comprehensive for identifying harmful variations in consanguineous families. This method is invaluable for providing accurate clinical diagnostic and genetic advice in remote regions of Pakistan while also increasing knowledge about autosomal recessive diseases and the dangers of mixing.
PubMed: 37267051
DOI: 10.7759/cureus.37933 -
The New England Journal of Medicine Mar 2018Familial erythrocytosis with elevated erythropoietin levels is frequently caused by mutations in genes that regulate oxygen-dependent transcription of the gene encoding...
Familial erythrocytosis with elevated erythropoietin levels is frequently caused by mutations in genes that regulate oxygen-dependent transcription of the gene encoding erythropoietin ( EPO). We identified a mutation in EPO that cosegregated with disease with a logarithm of the odds (LOD) score of 3.3 in a family with autosomal dominant erythrocytosis. This mutation, a single-nucleotide deletion (c.32delG), introduces a frameshift in exon 2 that interrupts translation of the main EPO messenger RNA (mRNA) transcript but initiates excess production of erythropoietin from what is normally a noncoding EPO mRNA transcribed from an alternative promoter located in intron 1. (Funded by the Gebert Rüf Foundation and others.).
Topics: Clustered Regularly Interspaced Short Palindromic Repeats; Erythropoietin; Female; Frameshift Mutation; Gain of Function Mutation; Gene Deletion; Genes, Dominant; Genetic Linkage; Humans; Male; Microsatellite Repeats; Pedigree; Polycythemia; Protein Biosynthesis; RNA, Messenger
PubMed: 29514032
DOI: 10.1056/NEJMoa1709064 -
Current Biology : CB Dec 2021Many aspects of sleep are heritable, but only a few sleep-regulating genes have been reported. Here, we leverage mouse models to identify and confirm a previously...
Many aspects of sleep are heritable, but only a few sleep-regulating genes have been reported. Here, we leverage mouse models to identify and confirm a previously unreported gene affecting sleep duration-dihydropyrimidine dehydrogenase (Dpyd). Using activity patterns to quantify sleep in 325 Diversity Outbred (DO) mice-a population with high genetic and phenotypic heterogeneity-a linkage peak for total sleep in the active lights off period was identified on chromosome 3 (LOD score = 7.14). Mice with the PWK/PhJ ancestral haplotype at this location demonstrated markedly reduced sleep. Among the genes within the linkage region, available RNA sequencing data in an independent sample of DO mice supported a highly significant expression quantitative trait locus for Dpyd, wherein reduced expression was associated with the PWK/PhJ allele. Validation studies were performed using activity monitoring and EEG/EMG recording in Collaborative Cross mouse strains with and without the PWK/PhJ haplotype at this location, as well as EEG and EMG recording of sleep and wake in Dpyd knockout mice and wild-type littermate controls. Mice lacking Dpyd had 78.4 min less sleep during the lights-off period than wild-type mice (p = 0.007; Cohen's d = -0.94). There was no difference in other measured behaviors in knockout mice, including assays evaluating cognitive-, social-, and affective-disorder-related behaviors. Dpyd encodes the rate-limiting enzyme in the metabolic pathway that catabolizes uracil and thymidine to β-alanine, an inhibitory neurotransmitter. Thus, data support β-alanine as a neurotransmitter that promotes sleep in mice.
Topics: Animals; Dihydrouracil Dehydrogenase (NADP); Haplotypes; Mice; Mice, Knockout; Sleep; beta-Alanine
PubMed: 34653361
DOI: 10.1016/j.cub.2021.09.049 -
Journal of the Science of Food and... Mar 2019Pistachio has high economic value because of its high consumption rate and consumer demand. Therefore, it has become an important target for adulteration. Green pea and...
BACKGROUND
Pistachio has high economic value because of its high consumption rate and consumer demand. Therefore, it has become an important target for adulteration. Green pea and spinach are the most frequently used foods for pistachio adulteration as a result of their kernel color. The present study aimed to detect pistachio adulteration with green pea and spinach samples using laser induced breakdown spectroscopy (LIBS) combined with chemometric methods.
RESULTS
In the first step of the study, principal component analysis was employed for qualitative analysis of pure pistachio, green pea, spinach and adulterated pistachio samples, and discrimination was achieved successfully. A score plot clearly discriminating pure pistachio, green pea and spinach samples, as well as their blind samples, was drawn using principle component (PC)1 and PC2 which explained 86.86% and 12.16% of the variance, respectively. The results showed that the calibration curve for green pea adulterated pistachio provides successful determination of adulteration level and had an R of 0.995 and a limit of detection (LOD) of 2.04%, whereas the calibration curve for spinach adulterated pistachio had an R of 0.993 and a LOD of 1.64%.
CONCLUSION
The results of the present study demonstrate that LIBS with the chemometric methods showed a good performance based on the high value of prediction accuracy for pistachio adulteration. This technique has high potential as a rapid method for pistachio identification and detection of adulteration. © 2018 Society of Chemical Industry.
Topics: Food Contamination; Lasers; Limit of Detection; Pisum sativum; Pistacia; Principal Component Analysis; Spectrum Analysis; Spinacia oleracea
PubMed: 30324635
DOI: 10.1002/jsfa.9418