Sivan Vadakkadath Meethal

Sivan Vadakkadath Meethal
University of Wisconsin–Madison | UW · Department of Medicine

MSc, PhD

About

55
Publications
11,441
Reads
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1,176
Citations
Citations since 2017
5 Research Items
461 Citations
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20172018201920202021202220230204060
20172018201920202021202220230204060
20172018201920202021202220230204060
Additional affiliations
February 2018 - present
JangoBio LLC
Position
  • Managing Director
November 2012 - present
University of Wisconsin-Madison School of Medicine and Public Health
Position
  • Senior Researcher
November 2010 - December 2012
University of Wisconsin-Madison School of Medicine and Public Health
Position
  • Professor (Associate)

Publications

Publications (55)
Article
Background: While sex hormones are essential for normal cognitive health, those individuals with greater endocrine dyscrasia around menopause and with andropause are more likely to develop cognitive loss and Alzheimer's disease (AD). Objective: To assess whether circulating sex hormones may provide an etiologically significant, surrogate biomark...
Article
Full-text available
The original version of this article unfortunately contained error in Figure 4a to where some of the text was overlapping.
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Folate supplementation in F0 mating rodents increases regeneration of injured spinal axons in vivo in 4 or more generations of progeny (F1–F4) in the absence of interval folate administration to the progeny. Transmission of the enhanced regeneration phenotype to untreated progeny parallels axonal growth in neuron culture after in vivo folate admini...
Article
Post-reproductive lifespan varies greatly among species; human post-reproductive lifespan comprises ~30–50% of their total longevity, while semelparous salmon and dasyurid marsupials post-reproductive lifespan comprises <4% of their total longevity. To examine if the magnitude of hypothalamic-pituitary-gonadal (HPG) axis dyscrasia at the time of re...
Article
Full-text available
The early reproductive events starting with folliculogenesis and ending with blastocyst implantation into the uterine endometrium are regulated by a complex interplay among endocrine, paracrine and autocrine factors. This review examines the spatiotemporal integration of these signals required for successful reproduction. In coordination with hypot...
Article
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Multiple genetic and epigenetic factors involved in central nervous system (CNS) development influence the incidence of neural tube defects (NTDs). The beneficial effect of periconceptional folic acid on NTD prevention denotes a vital role for the single-carbon biochemical pathway in NTD genesis. Indeed, NTDs are associated with polymorphisms in a...
Article
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Amyotrophic lateral sclerosis (ALS; Lou Gehrig's disease) is a progressive debilitating neurodegenerative disease with no cure. We propose a novel molecular model for the pathogenesis of ALS that involves an adenosine triphosphate (ATP)-dependent muscle neuronal lactate shuttle (MNLS) at the neuromuscular junction (NMJ) to regulate the flow of lact...
Chapter
IntroductionHormonal Regulation of Human EmbryogenesisProgesterone: an Essential Neurotrophic Hormone during All Phases of LifeAge-Related Loss of Progesterone: Implications in the Pathophysiology of Neurodegenerative DiseasesConclusion References
Article
Full-text available
The physiological signals that direct the division and differentiation of the zygote to form a blastocyst, and subsequent embryonic stem cell division and differentiation during early embryogenesis, are unknown. Although a number of growth factors, including the pregnancy-associated hormone human chorionic gonadotropin (hCG) are secreted by trophob...
Data
Prediction of transmembrane domains (TMs) in human GnRHR1 and Ce-GnRHR. The sequence alignment of human GnRHR1 and Ce-GnRHR presented here is taken from Figure 1; Thus for consistency, some sites are represented by gaps in both sequences. Functionally important residues (FIRs) are colored (see legend for classification). Overall, there is 56 % simi...
Article
Full-text available
The amyloid-beta precursor protein (AbetaPP) is a ubiquitously expressed transmembrane protein whose cleavage product, the amyloid-beta (Abeta) protein, is deposited in amyloid plaques in neurodegenerative conditions such as Alzheimer disease, Down syndrome, and head injury. We recently reported that this protein, normally associated with neurodege...
Article
Brain sex steroids are derived from both peripheral (primarily gonadal) and local (neurosteroids) sources and are crucial for neurogenesis, neural differentiation and neural function. The mechanism(s) regulating the production of neurosteroids is not understood. To determine whether hypothalamic-pituitary-gonadal axis components previously detected...
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Mutational changes coupled with endocrine, paracrine, and/or autocrine signals regulate cell division during carcinogenesis. The hormone signals remain undefined, although the absolute requirement in vitro for fetal serum indicates the necessity for a fetal serum factor(s) in cell proliferation. Using prostatic cancer cell (PCC) lines as a model of...
Article
Full-text available
Division of the human zygote leads to the formation of the blastocyst that contains human embryonic stem cells (hESC) which develop into the embryo. Little is known about the physiological signals that direct hESC division and differentiation during early embryogenesis. A number of growth factors, including the pregnancy-associated hormone human ch...
Article
Full-text available
The growth factors that drive the division and differentiation of stem cells during early human embryogenesis are unknown. The secretion of endorphins, progesterone (P(4)), human chorionic gonadotropin, 17beta-estradiol, and gonadotropin-releasing hormone by trophoblasts that lie adjacent to the embryoblast in the blastocyst suggests that these pre...
Article
Reproductive hormones have been demonstrated to modulate both gap and tight junction protein expression in the ovary and other reproductive tissues, however the effects of changes in reproductive hormones on the selective permeability of the blood-brain barrier (BBB) remain unclear. Age-related declines in BBB integrity correlate with the loss of s...
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Full-text available
Genetic and biochemical studies support the apolipoprotein E (APOE) epsilon4 allele as a major risk factor for late-onset Alzheimer's disease (AD), though ~50% of AD patients do not carry the allele. APOE transports cholesterol for luteinizing hormone (LH)-regulated steroidogenesis, and both LH and neurosteroids have been implicated in the etiology...
Article
The amyloid-beta precursor protein (AbetaPP) is a ubiquitously expressed adhesion and neuritogenic protein whose processing has previously been shown to be regulated by reproductive hormones including the gonadotropin luteinizing hormone (LH) in human neuroblastoma cells. We report for the first time the expression of AbetaPP in human embryonic ste...
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Full-text available
Leuprolide acetate is a synthetic nonapeptide that is a potent gonadotropin-releasing hormone receptor (GnRHR) agonist used for diverse clinical applications, including the treatment of prostate cancer, endometriosis, uterine fibroids, central precocious puberty and in vitro fertilization techniques. As its basic mechanism of action, leuprolide ace...
Article
We describe the two-dimensional imaging of excitation-induced Ca gradients in isolated myocytes under physiological conditions, using a novel method of flash photography of fluo-3 fluorescence. This method is useful for showing the spatial distribution and reproducibility of rapidly triggered Ca release events, and their relationship to underlying...
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Full-text available
Gonadotropin-releasing hormone receptor I (GnRHR I) has been localized to the limbic system of the rat brain, although the functional consequences of GnRH signaling through these receptors is unknown. In this paper, we characterize the expression of GnRHR I in the human hippocampus and cortex, and the functionality of GnRHR I in human neuroblastoma...
Data
Comparison of sequence and genomic organization between Ce-GnRHR and the putative orthologue to human GnRHR2 (orthologue 2). (A). Pairwise sequence alignment of Ce-GnRHR and orthologue 2 [GenBank; NP_506566]. The Ce-GnRHR sequence used to raise the anti-Ce-GnRHR antibody is highlighted with a green box. (B). Comparative genomic organization of Ce-G...
Data
Expression of the GnRHR1 orthologue in C. elegans. Worm (N2) homogenates were immunoblotted with a monoclonal antibody against human GnRHR1. The antibody recognized a 46-kDa band, the calculated molecular weight of the GnRHR1 orthologue. The secondary antibody control did not show immunoreactivity. The molecular weight markers are indicated in kDa...
Data
Full-text available
Class A and B GPCR dataset used to construct phylogenetic tree (Fig. 7). Sequences are given in FASTA format.
Article
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Background The Caenorhabditis elegans genome is known to code for at least 1149 G protein-coupled receptors (GPCRs), but the GPCR(s) critical to the regulation of reproduction in this nematode are not yet known. This study examined whether GPCRs orthologous to human gonadotropin-releasing hormone receptor (GnRHR) exist in C. elegans. Results Our s...
Article
Full-text available
Although not traditionally thought of as regulators of neuronal function, the hypothalamic-pituitary-gonadal (HPG) hormones luteinizing hormone (LH), gonadotropin-releasing hormone (GnRH), and activins possess neuronal receptors. These receptors are found throughout the limbic system on a number of different cell types, and, like reproductive tissu...
Article
Reduced sarcoplasmic reticulum (SR) Ca2+-ATPase (SERCA2a isoform) activity is a major determinant of reduced contractility in heart failure. Ca2+-ATPase inactivation can occur through SERCA2a nitration. We therefore investigated the role of SERCA2a nitration in heart failure. We measured SERCA2a levels and nitrotyrosine levels in tissue from normal...
Article
Full-text available
Senescence is characterized neurologically by a decline in cognitive function, which we propose is the result of degenerative processes initiated by the dysregulation of the hypothalamic-pituitary-gonadal (HPG) axis with menopause and andropause. Compelling epidemiologic evidence to support this assertion includes the increased prevalence of Alzhei...
Article
Full-text available
Receptors for hormones of the hypothalamic-pituitary-gonadal (HPG) axis that regulate reproductive function are expressed throughout the brain, and in particular the limbic system. The most studied of these hormones, the sex steroids, contain receptors throughout the brain, and numerous estrogenic, progestrogenic and androgenic effects have been re...
Article
The properties of the dyad cleft can in principle significantly impact excitation-contraction coupling, but these properties are not easily amenable to experimental investigation. We simultaneously measured the time course of the rise in integrated Ca current (ICa) and the rise in concentration of fura 2 with Ca bound ([Ca-fura 2]) with high time r...
Article
2,3-Dimethoxy-5-methyl-1,4-benzoquinone (Q0), an analogue of ubiquinone, irreversibly paralyses the adult and microfilariae of the cattle filarial parasite Setaria digitata. The same concentration of Q0 that paralyses the microfilariae of S. digitata also paralyses the microfilariae of the human filarial parasite Wuchereria bancrofti within the sam...
Article
In the filarial parasite, Setaria digitata, the mitochondria like particles (MLP) show NAD reduction with sodium lactate. The MLP also reduces dye and ferricyanide with lactate. The ferricyanide reduction by lactate is found to be sensitive to the cytochrome o inhibitor orthohydroxy diphenyl (OHD) and complex I inhibitor rotenone, modulated by ADP...
Article
In the cattle filarial parasite, Setaria digitata, the mitochondria-like particles have been shown to possess site I associated oxidative phosphorylation and rotenone sensitive and insensitive pathways for the dehydrogenation of NADH. Quinone depleted mitochondria-like particles show a loss of activity of these NADH dehydrogenases and also a comple...

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