The role of obesity in the fatal outcome of Schaaf-Yang syndrome: Early onset morbid obesity in a patient with aMAGEL2mutation

: Alzheimer’s disease (AD) is a progressive brain disorder and one of the most common causes of dementia and death. AD can be of two types; early-onset and late-onset, where late-onset AD occurs sporadically while early-onset AD results from a mutation in any of the three genes that include amyloid precursor protein (APP), presenilin 1 (PSEN 1) and presenilin 2 (PSEN 2). Biologically, AD is defined by the presence of the distinct neuropathological profile that consists of the extracellular β-amyloid (Aβ) deposition in the form of diffuse neuritic plaques, intraneuronal neurofibrillary tangles (NFTs) and neuropil threads; in dystrophic neuritis, consisting of aggregated hyperphosphorylated tau protein. Elevated levels of (Aβ), total tau (t-tau) and phosphorylated tau (ptau) in cerebrospinal fluid (CSF) have become an important biomarker for the identification of this neurodegenerative disease. The aggregation of Aβ peptide derived from amyloid precursor protein initiates a series of events that involve inflammation, tau hyperphosphorylation and its deposition, in addition to synaptic dysfunction and neurodegeneration, ultimately resulting in dementia. The current review focuses on the role of proteomes in the pathogenesis of AD.

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Inter-Tissue and Intra-Tissue Co-Expression Networks in Human Metabolism: Morphological Evaluation of the Link Between Transcription Factors ERβ and NFAT in Morbid Obesity

Current Diabetes Reviews ◽

10.2174/1573399816666200430112958 ◽

2020 ◽

Vol 17 (1) ◽

pp. 63-80

Author(s):

Athina Chasapi ◽

Kostas Balampanis ◽

Eleni Kourea ◽

Fotios Kalfaretzos ◽

Vaia Lambadiari ◽

...

Keyword(s):

Morbid Obesity ◽

Adipose Tissue ◽

Clinicopathological Parameters ◽

Morbidly Obese ◽

Human Metabolism ◽

Activated T Cells ◽

Alcoholic Fatty Liver ◽

Morphological Evaluation ◽

Underlying Mechanisms

Background: Estrogen receptor β (ERβ) plays an important role in human metabolism and some of its metabolic actions are mediated by a positive “cross-talk” with Nuclear Factor of Activated T cells (NFAT) and the key metabolic transcriptional coregulator Transcriptional Intermediary Factor 2 (TIF2). Introduction: Our study is an “in situ” morphological evaluation of the communication between ERβ, NFAT and TIF2 in morbid obesity. Potential correlations with clinicopathological parameters and with the presence of diabetes and non-alcoholic fatty liver disease (NAFLD) were also explored. The aim of the present study was to determine the role of ERβ and NFAT in the underlying pathophysiology of obesity and related comorbidities. We have investigated the expression of specific proteins using immunochemistry methodologies. Methods: Our population consists of 50 morbidly obese patients undergoing planned bariatric surgery, during which biopsies were taken from visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), skeletal muscle (SM), extramyocellular adipose tissue (EMAT) and liver and the differential protein expression was evaluated by immunohistochemistry. Results: We demonstrated an extensive intra- and inter-tissue co-expression network, which confirms the tissue-specific and integral role of each one of the investigated proteins in morbid obesity. Moreover, a beneficial role of ERβ and NFATc1 against NAFLD is implicated, whereas the distinct roles of TIF2 still remain an enigma. Conclusions: We believe that our findings will shed light on the complex underlying mechanisms and that the investigated biomarkers could represent future targets for the prevention and therapy of obesity and its comorbidities.

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Early onset of overweight among children from low‐income families: The role of exclusive breastfeeding and maternal intake of ultra‐processed food

Pediatric Obesity ◽

10.1111/ijpo.12825 ◽

2021 ◽

Author(s):

Jayanne Mayara Magalhães Melo ◽

Bruna Larine Lemos Fontes Silva Dourado ◽

Risia Cristina Egito Menezes ◽

Giovana Longo‐Silva ◽

Jonas Augusto Cardoso Silveira

Keyword(s):

Low Income ◽

Exclusive Breastfeeding ◽

Early Onset ◽

Processed Food ◽

Low Income Families

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Comparative effects of incretin-based therapy on early-onset diabetic nephropathy in rats: Role of TNF-α, TGF-β and c-caspase-3

Life Sciences ◽

10.1016/j.lfs.2021.119624 ◽

2021 ◽

pp. 119624

Author(s):

Heba A. Habib ◽

Gehan H. Heeba ◽

Mohamed M.A. Khalifa

Keyword(s):

Diabetic Nephropathy ◽

Early Onset ◽

Caspase 3 ◽

Tnf Α

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Novel TTLL5 Variants Associated with Cone-Rod Dystrophy and Early-Onset Severe Retinal Dystrophy

International Journal of Molecular Sciences ◽

10.3390/ijms22126410 ◽

2021 ◽

Vol 22 (12) ◽

pp. 6410

Author(s):

Vasily Smirnov ◽

Olivier Grunewald ◽

Jean Muller ◽

Christina Zeitz ◽

Carolin D. Obermaier ◽

...

Keyword(s):

Early Onset ◽

Retinal Dystrophy ◽

Copy Number Variants ◽

Cone Dystrophy ◽

The Novel ◽

Targeted Next Generation Sequencing ◽

Large Deletions ◽

Gene Panels ◽

Generation Sequencing

Variants of the TTLL5 gene, which encodes tubulin tyrosine ligase-like family member five, are a rare cause of cone dystrophy (COD) or cone-rod dystrophy (CORD). To date, only a few TTLL5 patients have been clinically and genetically described. In this study, we report five patients harbouring biallelic variants of TTLL5. Four adult patients presented either COD or CORD with onset in the late teenage years. The youngest patient had a phenotype of early onset severe retinal dystrophy (EOSRD). Genetic analysis was performed by targeted next generation sequencing of gene panels and assessment of copy number variants (CNV). We identified eight variants, of which six were novel, including two large multiexon deletions in patients with COD or CORD, while the EOSRD patient harboured the novel homozygous p.(Trp640*) variant and three distinct USH2A variants, which might explain the observed rod involvement. Our study highlights the role of TTLL5 in COD/CORD and the importance of large deletions. These findings suggest that COD or CORD patients lacking variants in known genes may harbour CNVs to be discovered in TTLL5, previously undetected by classical sequencing methods. In addition, variable phenotypes in TTLL5-associated patients might be due to the presence of additional gene defects.

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The role of germline mutations in the BRCA1/2 and mismatch repair genes in men ascertained for early-onset and/or familial prostate cancer

Familial Cancer ◽

10.1007/s10689-015-9832-x ◽

2015 ◽

Vol 15 (1) ◽

pp. 111-121 ◽

Cited By ~ 15

Author(s):

Sofia Maia ◽

Marta Cardoso ◽

Paula Paulo ◽

Manuela Pinheiro ◽

Pedro Pinto ◽

...

Keyword(s):

Prostate Cancer ◽

Mismatch Repair ◽

Early Onset ◽

Germline Mutations ◽

Mismatch Repair Genes ◽

Repair Genes

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An Obesity-RelatedFTOVariant and the Risk of Preeclampsia in a Finnish Study Population

Journal of Pregnancy ◽

10.1155/2011/251470 ◽

2011 ◽

Vol 2011 ◽

pp. 1-7 ◽

Cited By ~ 3

Author(s):

Miira Klemetti ◽

Leena M. Hiltunen ◽

Sanna Heino ◽

Seppo Heinonen ◽

Eero Kajantie ◽

...

Keyword(s):

Blood Pressure ◽

Type 2 Diabetes ◽

Early Onset ◽

Elevated Blood ◽

Study Population ◽

Normotensive Pregnancy ◽

Finnish Study ◽

Risk Of Preeclampsia

Previous studies have demonstrated a common variant of the obesity and fat mass-relatedFTOgene, rs9939609, to be associated with obesity, type 2 diabetes, and elevated blood pressure. We investigated whether theFTOSNP rs9939609 is associated with the risk of preeclampsia (PE) in a Finnish study population. 485 women with prior PE and 449 women who had given birth after a normotensive pregnancy were genotyped (TaqMan) for the SNP rs9939609. The prevalences of genotypes AA, AT, and TT were 15%, 53%, and 32%, respectively, among the PE cases, and 16%, 47%, and 37%, respectively, among the controls (P=0.199). We found no evidence of an association between theFTOSNP rs9939609 and PE. However, our cases were dominated by severe, early-onset PE. Thus, we are unable to exclude an association with the milder, later-onset form of the disease in which the role of maternal metabolic predisposition could be more significant.Erratum to “An Obesity-RelatedFTOVariant and the Risk of Preeclampsia in a Finnish Study Population”

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The role of neurohumours in early embryogenesis

Development ◽

10.1242/dev.23.3.549 ◽

1970 ◽

Vol 23 (3) ◽

pp. 549-569

Author(s):

G. A. Buznikov ◽

A. N. Kost ◽

N. F. Kucherova ◽

A. L. Mndzhoyan ◽

N. N. Suvorov ◽

...

Keyword(s):

Sea Urchin ◽

Functional Activity ◽

Early Onset ◽

Active Sites ◽

Physiological Effect ◽

Early Embryogenesis ◽

Dopamine Synthesis ◽

Direct Involvement ◽

Misgurnus Fossilis

In previous papers (Buznikov, Chudakova & Zvezdina, 1964; Buznikov, Chudakova, Berdysheva & Vyazmina, 1968) we reported that fertilized eggs of the sea-urchin Strongylocentrotus dröbachiensis synthesized a number of neurohumours, such as serotonin (5-hydroxytryptamine, 5-HT), acetylcholine (ACh), adrenalin (A), noradrenalin (NA) and dopamine. Synthesis of 5-HT was also demonstrated in the fertilized eggs of the loach Misgurnus fossilis and some marine Invertebrata. In experiments with sea-urchin embryos we were able to trace regular changes in the level of 5-HT, ACh, A and NA, related to the first cleavage divisions. This early onset of neurohumour synthesis, as well as regular changes in their level, suggests their direct involvement in the regulation of the first cleavage divisions. The functional activity of neurohumours (M) in adult organisms is realized through their reaction with the active sites of corresponding receptors (R) according to the following equation:The magnitude of the physiological effect under certain conditions is linearly proportional to the number of complexes MR formed (Turpayev, 1962; Ariëns, 1964).

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