Brain Peroxisomes

Peroxisomes are essential organelles in higher eukaryotes as they play a major role in numerous metabolic pathways and redox homeostasis. Some peroxisomal abnormalities, which are often not compatible with life or normal development, were identified in severe demyelinating and neurodegenerative brain diseases. The metabolic roles of peroxisomes, especially in the brain, are described and human brain peroxisomal disorders resulting from a peroxisome biogenesis or a single peroxisomal enzyme defect are listed. The brain abnormalities encountered in these disorders (demyelination, oxidative stress, inflammation, cell death, neuronal migration, differentiation) are described and their pathogenesis are discussed. Finally, the contribution of peroxisomal dysfunctions to the alterations of brain functions during aging and to the development of Alzheimer's disease is considered

Transcriptional expression of 8 genes predicts pathological response to first-line docetaxel + trastuzumab-based neoadjuvant chemotherapy

BACKGROUND: Overexpression of HER2 is observed in 20 to 30% of breast carcinomas. The use of trastuzumab has improved the treatment of these patients, especially when it is associated with docetaxel. To optimize the use of this treatment, it seems important to select putative complete responders before treatment administration. METHODS: In this study, we analyzed by quantitative PCR the expression of 28 genes in HER2-overexpressing tumors treated with trastuzumab + docetaxel-based chemotherapy. We then correlated their expression profile with those of trastuzumab-sensitive and resistant cell lines to classify tumors as having a sensitive (pCR) or resistant (non-pCR) profile. Finally, we used public datasets from the GEO website to validate the reduced gene-expression profile obtained. RESULTS: We identified an 8-gene-expression combination that predicted the response to treatment with an accuracy of 76%. Based on public microarray data, we showed that the expression profile was specific to first-line trastuzumab + docetaxel-based treatment with an accuracy of 85%. CONCLUSIONS: Our results showed that by profiling the expression of 8 genes it was possible to predict the response to first-line trastuzumab + docetaxel-based chemotherapy. The use of cancer cell lines as the reference allowed a proper fit with the specificity of different tissues, such as lung or gastric cancers, which could also be eligible to concomitant HER2 inhibition by treatment with trastuzumab or tyrosine kinase inhibitors and docetaxel. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12885-015-1198-9) contains supplementary material, which is available to authorized users

Contribution of Cholesterol and Oxysterols in the Physiopathology of Cataract: Implication for the Development of Pharmacological Treatments

The development of cataract is associated with some lipid changes in human lens fibers, especially with increased accumulation and redistribution of cholesterol inside these cells. Some direct and indirect lines of evidence, also suggest an involvement of cholesterol oxide derivatives (also named oxysterols) in the development of cataract. Oxysterol formation can result either from nonenzymatic or enzymatic processes, and some oxysterols can induce a wide range of cytotoxic effects (overproduction of reactive oxygen species (ROS); phospholipidosis) which might contribute to the initiation and progression of cataract. Thus, the conception of molecules capable of regulating cholesterol homeostasia and oxysterol levels in human lens fibers can have some interests and constitute an alternative to surgery at least at early stages of the disease

EFEKTIVITAS PROGRAM PEMBERDAYAAN MASYARAKAT MISKIN DI KELURAHAN PAAL DUA KECAMATAN PAAL DUA KOTA MANADO

AbstrakPemberdayaan masyarakat pada dasarnya bertujuan mewujudkan kesejahteraan, kedaulatan dan kemandirian, kesejahteraan tercemin dari peningkatan kualitas hidup lahir batin dan kemampuan masyarakat untuk memenuhi kebutuhan dasarnya, terutama di bidang ekonomi, pendidikan dan kesehatan, kedaulatan terbentuk dari derajat partisipasi yang mampu dilakukan masyarakat dalam pengambilan keputusan pembangunan, sedangkan kemandirian terwujud dari kemampuan swadaya dan gotong-royong masyarakat untuk mencukupi kebutuhan sendiri melalui pendayagunaan segenap potensi baik sumber daya alam, sumber daya manusia, kelembagaan masyarakat, modal finansial, maupun modal sosial yang ada. Tujuan penelitian ini adalah untuk mengetahui efektivitas program pemberdayaan masyarakat di Kelurahan Paal Dua Kecamatan Paal Dua Kota Manado, dengan menggunakan metode penelitian kualitatif diharapkan penelitian ini dapat menjawab secara paripurna mengenai masalah yang diteliti, hasil penelitian menunjukkan bahwa secara umum efektivitas pelaksanaan program pemberdayaan masyarakat miskin di Kelurahan Paal Dua yang dalam hal ini menjadi tanggung jawab dan wewenang pemerintah kelurahan bisa dikatakan kurang efektif, hal ini ditunjukkan dari kendala yang dihadapi yaitu pemahaman program kepada masyarakat yang dilakukan oleh pemerintah kelurahan belum berhasil dengan baik, karena proses sosialisasi program pemberdayaan seperti kelompok usaha bersama hanya dilakukan satu kali dengan alasan tidak tersedianya anggaran untuk melakukan sosialsiasi untuk memberikan pemahaman kepada masyarakat tersebut.Kata Kunci: Efektivitas, Program, Pemberdayaan Masyarakat Miskin

Implication de l'acide docosanoïque (C22 0) et des acides gras à très longue chaîne (acide tétracosanoïque (C24 0), acide hexacosanoïque ( C26 0) dans la maladie d'Alzheimer (aspects biologiques et cliniques)

Au niveau du cerveau et dans le plasma de malades atteints de maladie d Alzheimer (MA), l accumulation de C22:0 et d acides gras à très longue chaîne (C24:0 ; C26:0), la diminution d acide docosahexaenoique (C22:6 n-3) et les modifications quantitatives et qualitatives de plasmalogènes suggèrent l implication de dysfonctions peroxysomales. En fonction de ces constatations, les activités biologiques de C22:0, C24:0 et C26:0 ont été recherchées sur des cellules neuronales humaines SK-N-BE. La lipotoxicité des acides gras (C22:0, C24:0 et C26:0) induit divers effets au niveau des mitochondries (modifications topographiques, morphologiques et fonctionnelles), conduit à une rupture de l équilibre RedOx (surproduction d espèces radicalaires de l oxygène, modification de l activité des enzymes anti-oxydantes : catalase, SOD, GPx), à une peroxydation lipidique et à une désorganisation du cytosquelette (microfilaments d actine, tubuline, neurofilaments). Ces acides affectent aussi l amyloïdogenèse et la tauopathie. L amyloïde béta favorise aussi l accumulation intracellulaire de C22:0, C24:0 et C26:0. A fortes concentrations, ces acides gras induisent une mort cellulaire non apoptotique. Par ailleurs, les données immunohistochimiques en relation avec l expression de marqueurs peroxysomaux (ABCD1, ABCD2, ABCD3, ACOX1 et catalase) au niveau du cerveau de souris transgéniques APP PS1 E9 ainsi que les profil d acide gras obtenus sur le cerveau et le sang de ces souris suggèrent qu elles pourraient constituer un bon modèle pour l étude des relations entre MA et métabolisme peroxysomal. L étude clinique réalisée sur plasma et érythrocytes de malades déments (MA, démences vasculaires, autres démences) montre une forte accumulation de C22:0, C24:0 et C26:0. Le C26:0 pourrait constituer un excellent biomarqueur de la MA. Le C18:0 à est aussi augmenté ainsi que les acides gras n-6. De forts indices de stress oxydant sont aussi révélés. Dans son ensemble, le travail réalisé suggère que les acides gras (C22:0, C24:0 et C26:0) ainsi que le métabolisme des acides gras en relation avec le métabolisme peroxysomal pourraient contribuer à la neurodégénéréscence associée aux démences incluant la MAIn the brain and in the plasma of patients with Alzheimer s disease (AD), marked accumulation of C22:0 and of very long chain fatty acids (C24:0 ; C26:0) have been reported. Important decreases of docosahexaenoic acid (DHA; C22:6 n-3) have also been described as well as quantitative and qualitative modifications of plasmalogens. Altogether, these lipid modifications suggest an implication of peroxisomal metabolism disorders in the physiopathology of AD. Therefore, the biological activities of C22:0, C24:0 and C26:0 have been studied on human neuronal cells SK-N-BE. On these cells, the lipotoxicity of fatty acids (C22:0, C24:0 and C26:0) leads to various cellular modifications: topographical, morphological and functional changes at the mitochondrial level, rupture of RedOx equilibrium (overproduction of reactive oxygen species, modification of the activity of enzymes involved in anti-oxidant defenses: catalase, SOD, GPx), lipid peroxidation, cytoskeleton disorganization (actin microfilaments, tubulin, neurofilaments). These fatty acids also favor amyloidogenesis and tauopathy. At elevated concentrations, these fatty acids trigger a non apoptotic mode of cell death. Moreover, data obtained by immunohistochemistry with antibodies raised against peroxisomal components (ABCD1, ABCD2, ABCD3, ACOX1 and catalase) on histological tissue sections of the brain of transgenic mice APP PS1 E9 as well as lipidomic analysis performed on the blood and the brain of these mice suggest that they could constitute interesting model to study the relationships between AD and peroxisomal metabolism. The clinical study performed on the plasma and on the erythrocytes of patients with dementia (AD, vascular dementia, other dementia) revealed an important accumulation of C22:0, C24:0 and C26:0. Hexacosanoic acid (C26:0) might constitute an excellent biomarker of AD. The fatty acid C18:0 and (n-6) fatty acids have also been found at increased concentrations. A strong oxidative stress has also been revealed. Altogether, our data support that the fatty acids (C22:0, C24:0 and C26:0) as well as the fatty acid metabolism depending on the peroxisome might contribute to neurodegeneration leading to various types of dementia including ADDIJON-BU Doc.électronique (212319901) / SudocSudocFranceF

Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus

A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10-20), ER-negative BC (P=1.1 × 10-13), BRCA1-associated BC (P=7.7 × 10-16) and triple negative BC (P-diff=2 × 10-5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10-3) and ABHD8 (P<2 × 10-3). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3′-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk

Penerapan Convolutional Neural Network (CNN) dalam Klasifikasi Citra MRI untuk Deteksi Tumor Otak Manusia

Brain tumors are deadly diseases with a high mortality rate, making early diagnosis crucial to improving patient survival rates. However, manual diagnosis through Magnetic Resonance Imaging (MRI) often requires significant time and is prone to errors. This study developed an MRI image classification method using the EfficientNetB3-based Convolutional Neural Network (CNN) architecture to detect brain tumors. The dataset used was obtained from Kaggle, consisting of 253 brain MRI images, including 98 normal and 155 abnormal images. The data were preprocessed through normalization and resizing to 224x224 pixels. The model employed transfer learning techniques using pretrained weights from ImageNet, enhanced with additional layers to improve performance. Evaluation was conducted using metrics such as accuracy, precision, recall, F1-score, AUC, as well as confusion matrix and classification report analyses. The results showed that the EfficientNetB3 model achieved an overall accuracy of 86%, demonstrating its capability to support brain tumor diagnosis processes quickly and accurately. This implementation is expected to provide a significant contribution to early detection of brain tumors and improve patient care quality in the medical field

Implementasi K-Fold Dalam Prediksi Hasil Produksi Agrikultur Pada Algoritma K-Nearest Neighbor (KNN)

Sektor agrikultur khususnya pertanian di Indonesia merupakan tulang punggung perekonomian, dengan tenaga kerja pertanian mencapai 38,14 juta orang pada Februari 2023, atau 27,52% dari total tenaga kerja nasional. Meskipun memiliki potensi besar, sektor ini menghadapi tantangan signifikan, termasuk lahan terbatas, perubahan iklim, dan kelangkaan air, yang mengharuskan penerapan pertanian berkelanjutan. Penelitian ini bertujuan untuk meningkatkan efisiensi produksi pertanian melalui penerapan kecerdasan buatan (AI) dan analisis data. Metodologi yang digunakan meliputi pembagian data untuk memprediksi hasil produksi pertanian dengan algoritma k-nearest neighbour (KNN). Uji skenario dilakukan dengan pendekatan k-fold cross-validation dan hold-out data sharing. Hasil penelitian menunjukkan akurasi tertinggi sebesar 98,36% menggunakan k-fold cross-validation dan 97,42% dengan metode hold-out.Kata Kunci: KNN, K-Fold, Hold-Out, Prediksi, Agrikultu