{"id":16972,"date":"2024-07-15T13:49:08","date_gmt":"2024-07-15T18:49:08","guid":{"rendered":"https:\/\/last-drum.flywheelsites.com\/?p=16972"},"modified":"2024-08-07T10:37:37","modified_gmt":"2024-08-07T15:37:37","slug":"molecular-and-celluar-mechanisms","status":"publish","type":"post","link":"https:\/\/autism.org\/molecular-and-celluar-mechanisms\/","title":{"rendered":"The Low-Hanging Fruit: Exploring Monogenic Syndromes with Elevated Rates of Autism"},"content":{"rendered":"<p><div class=\"fusion-fullwidth fullwidth-box fusion-builder-row-1 nonhundred-percent-fullwidth non-hundred-percent-height-scrolling\" style=\"--awb-border-radius-top-left:0px;--awb-border-radius-top-right:0px;--awb-border-radius-bottom-right:0px;--awb-border-radius-bottom-left:0px;--awb-flex-wrap:wrap;\" ><div class=\"fusion-builder-row fusion-row\"><div class=\"fusion-layout-column fusion_builder_column fusion-builder-column-0 fusion_builder_column_1_6 1_6 fusion-one-sixth fusion-column-first\" style=\"--awb-padding-top:80px;--awb-bg-size:cover;width:13.3333%; margin-right: 4%;\"><div class=\"fusion-column-wrapper fusion-flex-column-wrapper-legacy\"><div class=\"fusion-sep-clear\"><\/div><div class=\"fusion-separator fusion-full-width-sep\" style=\"margin-left: auto;margin-right: auto;margin-top:40px;width:100%;\"><\/div><div class=\"fusion-sep-clear\"><\/div><div class=\"fusion-clearfix\"><\/div><\/div><\/div><div class=\"fusion-layout-column fusion_builder_column fusion-builder-column-1 fusion_builder_column_2_3 2_3 fusion-two-third\" style=\"--awb-padding-top:80px;--awb-bg-size:cover;width:65.3333%; margin-right: 4%;\"><div class=\"fusion-column-wrapper fusion-flex-column-wrapper-legacy\"><div class=\"fusion-text fusion-text-1\" style=\"--awb-text-transform:none;\"><p><span style=\"font-weight: 400;\"><a href=\"#jump\">Dr. Daniel Vogt, Ph.D.<\/a>, explores monogenic syndromes and what they can tell us about the underlying causes of autism. He describes signaling pathways critical in early development, highlighting the electrical nature of cell communication and function. The presenter explains how testing the impact of autism risk gene variations on cell signaling pathways can help us understand the roles and outcomes of specific genetic mutations in autism. Vogt presents recent research suggesting disruptions to cell circuitry in autism and highlights the need for research into the connection between cell communication and autistic behaviors. He provides thanks and acknowledgments before the Q&amp;A.\u00a0<\/span><\/p>\n<p>Handouts are online <a href=\"https:\/\/autism.org\/molecular-and-celluar-mechanisms\/\">HERE<\/a><\/p>\n<\/div><div class=\"fusion-sep-clear\"><\/div><div class=\"fusion-separator fusion-full-width-sep\" style=\"margin-left: auto;margin-right: auto;width:100%;\"><\/div><div class=\"fusion-sep-clear\"><\/div><div class=\"fusion-video fusion-youtube fusion-aligncenter\" style=\"--awb-max-width:600px;--awb-max-height:360px;--awb-width:100%;\"><div class=\"video-shortcode\"><div class=\"fluid-width-video-wrapper\" style=\"padding-top:60%;\" ><iframe title=\"YouTube video player 1\" src=\"https:\/\/www.youtube.com\/embed\/4R08TVJAL_o?wmode=transparent&autoplay=0\" width=\"600\" height=\"360\" allowfullscreen allow=\"autoplay; fullscreen\"><\/iframe><\/div><\/div><\/div><div class=\"fusion-sep-clear\"><\/div><div class=\"fusion-separator fusion-full-width-sep\" style=\"margin-left: auto;margin-right: auto;width:100%;\"><\/div><div class=\"fusion-sep-clear\"><\/div><div class=\"fusion-text fusion-text-2\" style=\"--awb-text-transform:none;\"><h2><strong>In this webinar:<\/strong><\/h2>\n<p><strong>1:00<\/strong> &#8211; Genetic causes of autism<br \/>\n<strong>3:00<\/strong> &#8211; Critical signaling pathways<br \/>\n<strong>5:15<\/strong> &#8211; Cortical interneurons<br \/>\n<strong>9:08<\/strong> &#8211; Parvalbumin theory<br \/>\n<strong>13:05<\/strong> &#8211; mTOR signaling pathway mutations<br \/>\n<strong>20:50<\/strong> &#8211; MAPK signaling pathway mutations<br \/>\n<strong>27:35<\/strong> &#8211; Electrical properties<br \/>\n<strong>32:40<\/strong> &#8211; Conclusions<br \/>\n<strong>40:15<\/strong> &#8211; Future research<br \/>\n<strong>44:00<\/strong> &#8211; Q&amp;A<\/p>\n<h2><b>Genetic causes of autism<\/b><\/h2>\n<p><span style=\"font-weight: 400;\">Proteins associated with synapses and cellular signaling have been identified as genetic drivers of autism. Vogt and his research lab focus on cell signaling to identify links between events that occur on the cell surface and cytoplasm (inside the cell) <\/span><b>(2:00)<\/b><span style=\"font-weight: 400;\">. The speaker introduces two signaling cascades critical to cell growth, division and migration <\/span><b>(3:00)<\/b><span style=\"font-weight: 400;\">:\u00a0<\/span><\/p>\n<ul>\n<li style=\"font-weight: 400;\" aria-level=\"1\"><b>mTOR<\/b><span style=\"font-weight: 400;\"> (Mammalian target of rapamycin): leads to translational regulation; inhibited by <\/span><i><span style=\"font-weight: 400;\">known autism risk genes Pten<\/span><\/i><span style=\"font-weight: 400;\"> in early development and <\/span><i><span style=\"font-weight: 400;\">Tsc1<\/span><\/i><span style=\"font-weight: 400;\"> in late development<\/span><\/li>\n<li style=\"font-weight: 400;\" aria-level=\"1\"><b>MAPK<\/b><span style=\"font-weight: 400;\"> (Mitogen-activated protein kinase): leads to transcriptional regulation; inhibited by <\/span><i><span style=\"font-weight: 400;\">known autism risk gene<\/span><\/i> <i><span style=\"font-weight: 400;\">Nf1<\/span><\/i><span style=\"font-weight: 400;\"> at early stages of development<\/span><\/li>\n<\/ul>\n<h2><b>Cortical interneurons (CINs)<\/b><\/h2>\n<p><span style=\"font-weight: 400;\">To determine what, if any, mutations or effects are common across pathways, Vogt and colleagues study GABAergic cortical interneuron ratios in mice <\/span><b>(5:15)<\/b><span style=\"font-weight: 400;\">. Cortical interneurons (CINs) shape neural networks in the brain and originate from embryonic brain structures called the medial and caudal ganglionic eminences (MGE\/CGE) <\/span><b>(6:20)<\/b><span style=\"font-weight: 400;\">. The speaker explains that the MGE develops around 70% of CINs via four major events:\u00a0<\/span><\/p>\n<ul>\n<li style=\"font-weight: 400;\" aria-level=\"1\"><i><span style=\"font-weight: 400;\">Cell proliferation<\/span><\/i><span style=\"font-weight: 400;\"> (birth) and apoptosis (death)<\/span><\/li>\n<li style=\"font-weight: 400;\" aria-level=\"1\"><i><span style=\"font-weight: 400;\">Cell migration <\/span><\/i><span style=\"font-weight: 400;\">across long distances to final targets in the brain<\/span><\/li>\n<li style=\"font-weight: 400;\" aria-level=\"1\"><i><span style=\"font-weight: 400;\">Cell fate<\/span><\/i><span style=\"font-weight: 400;\">, or the acquisition of specific properties related to cell function<\/span><\/li>\n<li style=\"font-weight: 400;\" aria-level=\"1\"><i><span style=\"font-weight: 400;\">Electrical properties<\/span><\/i><span style=\"font-weight: 400;\"> used to communicate across the microcircuit synapses<\/span><\/li>\n<\/ul>\n<p><span style=\"font-weight: 400;\">Vogt describes a study that found significantly decreased numbers of Parvalbumin (PV+) CINs (important for brain circuitry and memory) in autistic participants compared to controls <\/span><b>(9:08)<\/b><span style=\"font-weight: 400;\">. He touches on the Paravalbumin hypothesis of autism, which asserts that disruption of PV+ CINs may be a root cause of autism symptoms <\/span><b>(10:14)<\/b><span style=\"font-weight: 400;\">. Somatostatin (SST+) cells are another subgroup of CINs with a slower electric firing frequency. The presenter outlines mouse model methods for assessing the impact of mutant pathways on CIN subgroup ratios <\/span><b>(11:15)<\/b><span style=\"font-weight: 400;\">.\u00a0<\/span><\/p>\n<ul>\n<li style=\"font-weight: 400;\" aria-level=\"1\"><a href=\"https:\/\/www.nature.com\/articles\/nrn1954\"><i><span style=\"font-weight: 400;\">The origin and specification of cortical interneurons<\/span><\/i><\/a> <span style=\"font-weight: 400;\">(Wonders &amp; Anderson, 2006)<\/span><\/li>\n<li style=\"font-weight: 400;\" aria-level=\"1\"><a href=\"https:\/\/www.nature.com\/articles\/nn.4191\"><i><span style=\"font-weight: 400;\">Brief optogenetic inhibition of dopamine neurons mimics endogenous negative reward prediction errors<\/span><\/i><\/a> <span style=\"font-weight: 400;\">(Chang et al., 2015)<\/span><\/li>\n<li style=\"font-weight: 400;\" aria-level=\"1\"><a href=\"https:\/\/academic.oup.com\/cercor\/article\/27\/3\/1931\/3052664\"><i><span style=\"font-weight: 400;\">The Number of Parvalbumin-Expressing Interneurons Is Decreased in the Prefrontal Cortex in Autism<\/span><\/i><\/a> <span style=\"font-weight: 400;\">(Hashemi et al., 2016)<\/span><\/li>\n<li style=\"font-weight: 400;\" aria-level=\"1\"><a href=\"https:\/\/www.frontiersin.org\/journals\/cellular-neuroscience\/articles\/10.3389\/fncel.2020.577525\/full\"><i><span style=\"font-weight: 400;\">The Parvalbumin Hypothesis of Autism Spectrum Disorder<\/span><\/i><\/a> <span style=\"font-weight: 400;\">(Filice et al., 2020)<\/span><\/li>\n<\/ul>\n<p>For more information on brain development in autism, view <a href=\"https:\/\/autism.org\/tms-asd-2021\/\">Transcranial Magnetic Stimulation and Autism<\/a>, a free webinar presented by Manuel Casanova, MD.<\/p>\n<h2><b>mTOR signaling pathway<\/b><\/h2>\n<p><span style=\"font-weight: 400;\">The speaker asserts that converging evidence across multiple phenotypes associated with the loss of Pten suggests the electric cell communication circuit may be impaired in autism <\/span><b>(14:11)<\/b><span style=\"font-weight: 400;\">. Vogt outlines the process by which Pten is adjusted in mouse MGE cells to test for different variants and their functions <\/span><b>(15:45)<\/b><span style=\"font-weight: 400;\">. Mice with a Pten deletion showed no changes in SST expression, but had significantly reduced PV expression. However, mice with a human variant of Pten were rescued (returned) to control\/wild-type levels <\/span><b>(17:00)<\/b><span style=\"font-weight: 400;\">. These findings, Vogt claims, show that variations of Pten cannot maintain the pathway, meaning that it is a loss-of-function gene <\/span><b>(18:00)<\/b><span style=\"font-weight: 400;\">. Tsc1 mutations also cause increased PV expression, suggesting a hyperactive mTOR pathway <\/span><b>(19:30)<\/b><span style=\"font-weight: 400;\">. The speaker reviews that mTOR activity promotes PV+ CINs, that the loss of Pten and Tsc1 lead to hyperactive signaling (e.g., higher expression of PV and lower expression of SST),\u00a0 and that most genetic variants of Pten and Tsc1 are loss-of-function genes <\/span><b>(20:10)<\/b><span style=\"font-weight: 400;\">.\u00a0<\/span><\/p>\n<ul>\n<li style=\"font-weight: 400;\" aria-level=\"1\"><a href=\"https:\/\/www.cell.com\/cell-reports\/fulltext\/S2211-1247(15)00406-4\"><i><span style=\"font-weight: 400;\">The Parvalbumin\/Somatostatin Ratio Is Increased in Pten Mutant Mice and by Human PTEN ASD Alleles<\/span><\/i><\/a> <span style=\"font-weight: 400;\">(Vogt et al., 2015)<\/span><\/li>\n<li style=\"font-weight: 400;\" aria-level=\"1\"><a href=\"https:\/\/www.nature.com\/articles\/s41467-019-12962-4\"><i><span style=\"font-weight: 400;\">Tsc1 represses parvalbumin expression and fast-spiking properties in somatostatin lineage cortical interneurons<\/span><\/i><\/a> <span style=\"font-weight: 400;\">(Malik et al., 2019)<\/span><\/li>\n<\/ul>\n<h2><b>MAPK signaling pathway<\/b><\/h2>\n<p><span style=\"font-weight: 400;\">Deletion of the Nf1 gene or consecutive expression of bRaf leads to hyperactivation of the MAPK pathway. The speaker explains that hyperactive MAPK signaling causes increased levels of SST+ CINs and the repression of the <\/span><i><span style=\"font-weight: 400;\">ARX<\/span><\/i><span style=\"font-weight: 400;\"> gene,<\/span> <span style=\"font-weight: 400;\">which is critical for MGE and CGE development <\/span><b>(20:50)<\/b><span style=\"font-weight: 400;\">. Hyperactive MAPK pathways also have decreased PV expression, further evidencing circuit-based phenotypic variations <\/span><b>(23:30)<\/b><span style=\"font-weight: 400;\">. Vogt outlines a study that found decreased SST expression and normal PV levels after deletion of ERK1\/2 in a mouse model. He explains that the pathway&#8217;s simultaneous hyperactivity and reduced activity suggest a dosage problem that corresponds to SST levels <\/span><b>(25:07)<\/b><span style=\"font-weight: 400;\">.\u00a0<\/span><\/p>\n<p><span style=\"font-weight: 400;\">The speaker reviews MAPK loss-of-function mutations, highlighting that a hyperactive pathway leads to higher SST and lower PV expression. Conversely, loss of ERK1\/2 produces fewer SST+ and more PV+ cells <\/span><b>(26:20)<\/b><span style=\"font-weight: 400;\">. The speaker continues that some data suggest overproduction of SST in early development may outweigh the ability to make enough Pten later.\u00a0<\/span><\/p>\n<h3><b>Electrical properties<\/b><\/h3>\n<p><span style=\"font-weight: 400;\">The presenter explains that by assessing the electrical properties of CINs, we can determine pathways of cell fate and communication <\/span><b>(27:35)<\/b><span style=\"font-weight: 400;\">. As noted previously, PV+ CINs have faster electrical spike patterns compared to SST+ CINs. Therefore, Vogt explains, hyperactive mTOR pathways have higher firing properties (more PV), and hyperactive MAPK mutants have slower firing properties (more SST) <\/span><b>(30:00)<\/b><span style=\"font-weight: 400;\">. He asserts that these findings show common changes across these pathways that are important for cellular fates, properties, and functionality <\/span><b>(31:20)<\/b><span style=\"font-weight: 400;\">.\u00a0<\/span><\/p>\n<h2><b>What\u2019s next<\/b><\/h2>\n<p><span style=\"font-weight: 400;\">Researchers have observed that mice with hyperactive MAPK (Nf1 deletion) present behaviors that resemble hyperactivity and a reduced sense of danger, suggesting a link between molecular changes and behaviors <\/span><b>(32:40)<\/b><span style=\"font-weight: 400;\">. The presenter discusses changes to transcription factors in the MGE in hyperactive MAPK (Nf1) mice, highlighting that more research is needed to understand the connections between cellular circuitry and behavior <\/span><b>(35:25)<\/b><span style=\"font-weight: 400;\">.\u00a0<\/span><\/p>\n<p><span style=\"font-weight: 400;\">Vogt outlines unpublished research that uses Selumetinib, an FDA-approved MEK inhibitor, to test molecular changes in mice. Preliminary results show that ERK remains active in controls. At the same time, blot test bands were rescued in mice who consumed the drug <\/span><b>(36:50)<\/b><span style=\"font-weight: 400;\">. The same study also found that systemic delivery of Selumetinib led to some behavior rescue in Nf1 adult mice. The speaker notes that ARX markers also seem to respond to the drug <\/span><b>(38:50)<\/b><span style=\"font-weight: 400;\">. Future directions include switching mTOR mutants with known molecular and cellular changes and using rapamycin to inhibit mTOR and search for other changes that may correlate with behaviors <\/span><b>(40:15)<\/b><span style=\"font-weight: 400;\">. Vogt provides thanks and acknowledgments <\/span><b>(42:40) <\/b><span style=\"font-weight: 400;\">before the Q&amp;A <\/span><b>(44:00)<\/b><span style=\"font-weight: 400;\">.<\/span><\/p>\n<ul>\n<li style=\"font-weight: 400;\" aria-level=\"1\"><a href=\"https:\/\/journals.physiology.org\/doi\/full\/10.1152\/jn.00799.2014\"><i><span style=\"font-weight: 400;\">Functional properties of GABA synaptic inputs onto GABA neurons in monkey prefrontal cortex<\/span><\/i><\/a> <span style=\"font-weight: 400;\">(Rotaru et al., 2015)<\/span><\/li>\n<li style=\"font-weight: 400;\" aria-level=\"1\"><a href=\"https:\/\/journals.biologists.com\/dev\/article\/150\/10\/dev201371\/310864\/Distinct-hyperactive-RAS-MAPK-alleles-converge-on\"><i><span style=\"font-weight: 400;\">Distinct hyperactive RAS\/MAPK alleles converge on common GABAergic interneuron core programs Icon for The Forest of Biologists<\/span><\/i><\/a> <span style=\"font-weight: 400;\">(Knowles et al., 2023)<\/span><\/li>\n<li style=\"font-weight: 400;\" aria-level=\"1\"><a href=\"https:\/\/www.nature.com\/articles\/s41467-019-12962-4\"><i><span style=\"font-weight: 400;\">Tsc1 represses parvalbumin expression and fast-spiking properties in somatostatin lineage cortical interneurons<\/span><\/i><\/a> <span style=\"font-weight: 400;\">(Malik et al., 2019)<\/span><\/li>\n<\/ul>\n<p><em><strong>Originally published on February 21, 2024<\/strong><\/em><\/p>\n<\/div><div class=\"fusion-sep-clear\"><\/div><div class=\"fusion-separator fusion-full-width-sep\" style=\"margin-left: auto;margin-right: auto;width:100%;\"><\/div><div class=\"fusion-sep-clear\"><\/div><div class=\"fusion-clearfix\"><\/div><\/div><\/div><div class=\"fusion-layout-column fusion_builder_column fusion-builder-column-2 fusion_builder_column_1_6 1_6 fusion-one-sixth fusion-column-last\" style=\"--awb-padding-top:80px;--awb-bg-size:cover;width:13.3333%;\"><div class=\"fusion-column-wrapper fusion-flex-column-wrapper-legacy\"><div class=\"fusion-sep-clear\"><\/div><div class=\"fusion-separator fusion-full-width-sep\" style=\"margin-left: auto;margin-right: auto;margin-top:40px;width:100%;\"><\/div><div class=\"fusion-sep-clear\"><\/div><div class=\"fusion-clearfix\"><\/div><\/div><\/div><\/div><\/div><div id=\"jump\" class=\"fusion-container-anchor\"><div class=\"fusion-fullwidth fullwidth-box fusion-builder-row-2 has-pattern-background has-mask-background nonhundred-percent-fullwidth non-hundred-percent-height-scrolling\" style=\"--awb-border-radius-top-left:0px;--awb-border-radius-top-right:0px;--awb-border-radius-bottom-right:0px;--awb-border-radius-bottom-left:0px;--awb-flex-wrap:wrap;\" ><div class=\"fusion-builder-row fusion-row\"><div class=\"fusion-layout-column fusion_builder_column fusion-builder-column-3 fusion_builder_column_1_3 1_3 fusion-one-third fusion-column-first\" style=\"--awb-bg-size:cover;width:33.333333333333%;width:calc(33.333333333333% - ( ( 4% ) * 0.33333333333333 ) );margin-right: 4%;\"><div class=\"fusion-column-wrapper fusion-column-has-shadow fusion-flex-column-wrapper-legacy\"><div class=\"fusion-text fusion-text-3\" style=\"--awb-text-transform:none;\"><h3>The speaker:<\/h3>\n<p><img decoding=\"async\" class=\"lazyload  wp-image-14348 alignleft\" src=\"https:\/\/autism.org\/wp-content\/uploads\/2021\/12\/Vogt_D_1_of_1-150x150.jpg\" data-orig-src=\"https:\/\/autism.org\/wp-content\/uploads\/2021\/12\/Vogt_D_1_of_1-150x150.jpg\" alt=\"\" width=\"98\" height=\"98\" srcset=\"data:image\/svg+xml,%3Csvg%20xmlns%3D%27http%3A%2F%2Fwww.w3.org%2F2000%2Fsvg%27%20width%3D%2798%27%20height%3D%2798%27%20viewBox%3D%270%200%2098%2098%27%3E%3Crect%20width%3D%2798%27%20height%3D%2798%27%20fill-opacity%3D%220%22%2F%3E%3C%2Fsvg%3E\" data-srcset=\"https:\/\/autism.org\/wp-content\/uploads\/2021\/12\/Vogt_D_1_of_1-66x66.jpg 66w, https:\/\/autism.org\/wp-content\/uploads\/2021\/12\/Vogt_D_1_of_1-150x150.jpg 150w, https:\/\/autism.org\/wp-content\/uploads\/2021\/12\/Vogt_D_1_of_1-200x201.jpg 200w, https:\/\/autism.org\/wp-content\/uploads\/2021\/12\/Vogt_D_1_of_1.jpg 220w\" data-sizes=\"auto\" data-orig-sizes=\"(max-width: 98px) 100vw, 98px\" \/>Dr. Daniel Vogt, PhD, is an Assistant Professor in the College of Human Medicine\u2019s Department of Pediatrics and Human Development. Dr. Vogt\u2019s lab is investigating the molecular and cellular mechanisms underlying autism. The lab is particularly interested in understanding how genes implicated in autism are functioning in the brain and how mutations in these genes lead to symptoms of autism and related conditions. One hypothesis is that some characteristics of autism are caused by an imbalance in neuronal excitation and inhibition. To this end, Dr. Vogt\u2019s lab is focusing on understanding how inhibitory neurons develop and function. In addition, the lab seeks to understand how mutations discovered in autism genes alter their function.<\/p>\n<p>Dr. Vogt\u2019s research has elucidated how key developmental genes influence inhibitory neuron development. In particular, his research was important in uncovering how the gene, Lhx6, a transcription factor required for inhibitory neuron development, controls the cell fate of inhibitory neurons derived from the median ganglionic eminence (MGE) (Neuron, 2014). Dr. Vogt also developed an in vivo approach to assess the impact that human mutations discovered in autism patients have on gene function. This approach was tested with the autism candidate gene, PTEN, and demonstrated that mutations in PTEN resulted in defects in inhibitory neuron development (Cell Reports. 2015). The lab\u2019s goal is to continue to screen mutations in genes implicated in autism to uncover both common and unique symptoms that are caused by genes. Finally, the lab seeks to combine the knowledge gained from the screening of mutations and the knowledge from studying individual genes to uncover new insights into inhibitory neuron development.<\/p>\n<\/div><div class=\"fusion-clearfix\"><\/div><\/div><\/div><div class=\"fusion-layout-column fusion_builder_column fusion-builder-column-4 fusion_builder_column_2_3 2_3 fusion-two-third fusion-column-last\" style=\"--awb-bg-size:cover;width:66.666666666667%;width:calc(66.666666666667% - ( ( 4% ) * 0.66666666666667 ) );\"><div class=\"fusion-column-wrapper fusion-column-has-shadow fusion-flex-column-wrapper-legacy\"><div class=\"fusion-text fusion-text-4\"><h4>Take the knowledge quiz<\/h4>\n<p>Can&#8217;t see the quiz below? 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href=\"https:\/\/www.linkedin.com\/company\/autism-research-institute\/\"><\/a><\/div><\/div><\/div><div class=\"fusion-separator fusion-full-width-sep\" style=\"align-self: center;margin-left: auto;margin-right: auto;margin-top:30px;width:100%;\"><\/div><\/div><\/div><\/div><\/div>\n<div class=\"fusion-fullwidth fullwidth-box fusion-builder-row-4 nonhundred-percent-fullwidth non-hundred-percent-height-scrolling\" style=\"--awb-border-radius-top-left:0px;--awb-border-radius-top-right:0px;--awb-border-radius-bottom-right:0px;--awb-border-radius-bottom-left:0px;--awb-flex-wrap:wrap;\" ><div class=\"fusion-builder-row fusion-row\"><div class=\"fusion-layout-column fusion_builder_column fusion-builder-column-6 fusion_builder_column_1_1 1_1 fusion-one-full fusion-column-first fusion-column-last\" style=\"--awb-bg-size:cover;\"><div class=\"fusion-column-wrapper fusion-column-has-shadow fusion-flex-column-wrapper-legacy\"><div class=\"fusion-sep-clear\"><\/div><div class=\"fusion-separator fusion-full-width-sep\" style=\"margin-left: auto;margin-right: auto;margin-top:30px;width:100%;\"><\/div><div class=\"fusion-sep-clear\"><\/div><div class=\"fusion-recent-posts fusion-recent-posts-1 avada-container layout-default layout-columns-3\"><section class=\"fusion-columns columns fusion-columns-3 columns-3\"><article class=\"post fusion-column column col col-lg-4 col-md-4 col-sm-4\"><div class=\"fusion-flexslider fusion-flexslider-loading flexslider flexslider-hover-type-none\"><ul class=\"slides\"><li><a href=\"https:\/\/autism.org\/breakthroughs-in-understanding-roles-of-genes-and-environment-in-autism\/\" aria-label=\"Breakthroughs in Understanding roles of Genes and Environment in Autism\" class=\"hover-type-none\"><img decoding=\"async\" width=\"700\" height=\"441\" src=\"https:\/\/autism.org\/wp-content\/uploads\/2019\/01\/paid_-dna-700x441.jpg\" class=\"attachment-recent-posts size-recent-posts lazyload\" alt=\"autism genetic research, beyond genetics autism\" srcset=\"data:image\/svg+xml,%3Csvg%20xmlns%3D%27http%3A%2F%2Fwww.w3.org%2F2000%2Fsvg%27%20width%3D%271600%27%20height%3D%271067%27%20viewBox%3D%270%200%201600%201067%27%3E%3Crect%20width%3D%271600%27%20height%3D%271067%27%20fill-opacity%3D%220%22%2F%3E%3C%2Fsvg%3E\" data-orig-src=\"https:\/\/autism.org\/wp-content\/uploads\/2019\/01\/paid_-dna-700x441.jpg\" data-srcset=\"https:\/\/autism.org\/wp-content\/uploads\/2019\/01\/paid_-dna-320x202.jpg 320w, https:\/\/autism.org\/wp-content\/uploads\/2019\/01\/paid_-dna-700x441.jpg 700w\" data-sizes=\"auto\" \/><\/a><\/li><\/ul><\/div><div class=\"recent-posts-content\"><span class=\"vcard\" style=\"display: none;\"><span class=\"fn\"><a href=\"https:\/\/autism.org\/author\/melanie\/\" title=\"Posts by Melanie Glock\" rel=\"author\">Melanie Glock<\/a><\/span><\/span><span class=\"updated\" style=\"display:none;\">2026-01-05T18:58:39-05:00<\/span><h4 class=\"entry-title\"><a href=\"https:\/\/autism.org\/breakthroughs-in-understanding-roles-of-genes-and-environment-in-autism\/\">Breakthroughs in Understanding roles of Genes and Environment in Autism<\/a><\/h4><p class=\"meta\"><span class=\"vcard\" style=\"display: none;\"><span class=\"fn\"><a href=\"https:\/\/autism.org\/author\/melanie\/\" title=\"Posts by Melanie Glock\" rel=\"author\">Melanie Glock<\/a><\/span><\/span><span class=\"updated\" style=\"display:none;\">2026-01-05T18:58:39-05:00<\/span><span>December 2nd, 2025<\/span><span class=\"fusion-inline-sep\">|<\/span><a href=\"https:\/\/autism.org\/category\/webinar\/environmental-factors\/\" rel=\"category tag\">Environmental Factors<\/a>, <a href=\"https:\/\/autism.org\/category\/webinar\/genetics\/\" rel=\"category tag\">Genetics<\/a>, <a href=\"https:\/\/autism.org\/category\/health\/\" rel=\"category tag\">Health<\/a>, <a href=\"https:\/\/autism.org\/category\/medical-care\/\" rel=\"category tag\">Medical Care<\/a>, <a href=\"https:\/\/autism.org\/category\/webinar\/neurological\/\" rel=\"category tag\">Neurological<\/a>, <a href=\"https:\/\/autism.org\/category\/research\/\" rel=\"category tag\">Research<\/a>, <a href=\"https:\/\/autism.org\/category\/webinar\/research-webinar\/\" rel=\"category tag\">Research<\/a>, <a href=\"https:\/\/autism.org\/webinars\/\" rel=\"category tag\">Webinar<\/a><span class=\"fusion-inline-sep\">|<\/span><\/p><p>          About the speaker: Dr. Jonathan Sebat, Director, Beyster Center for Psychiatric Genomics Dr. Sebat leads an interdisciplinary team in the clinical and genomic analysis of<\/p><\/div><\/article><article class=\"post fusion-column column col col-lg-4 col-md-4 col-sm-4\"><div class=\"fusion-flexslider fusion-flexslider-loading flexslider flexslider-hover-type-none\"><ul class=\"slides\"><li><a href=\"https:\/\/autism.org\/molecular-and-celluar-mechanisms\/\" aria-label=\"The Low-Hanging Fruit: Exploring Monogenic Syndromes with Elevated Rates of Autism\" class=\"hover-type-none\"><img decoding=\"async\" width=\"700\" height=\"441\" src=\"https:\/\/autism.org\/wp-content\/uploads\/2019\/06\/AdobeStock_845339561-700x441.jpeg\" class=\"attachment-recent-posts size-recent-posts lazyload\" alt=\"Two puzzle pieces with the words &quot;Autism&quot; and &quot;Genetics&quot; on them\" srcset=\"data:image\/svg+xml,%3Csvg%20xmlns%3D%27http%3A%2F%2Fwww.w3.org%2F2000%2Fsvg%27%20width%3D%271192%27%20height%3D%27924%27%20viewBox%3D%270%200%201192%20924%27%3E%3Crect%20width%3D%271192%27%20height%3D%27924%27%20fill-opacity%3D%220%22%2F%3E%3C%2Fsvg%3E\" data-orig-src=\"https:\/\/autism.org\/wp-content\/uploads\/2019\/06\/AdobeStock_845339561-700x441.jpeg\" data-srcset=\"https:\/\/autism.org\/wp-content\/uploads\/2019\/06\/AdobeStock_845339561-320x202.jpeg 320w, https:\/\/autism.org\/wp-content\/uploads\/2019\/06\/AdobeStock_845339561-700x441.jpeg 700w\" data-sizes=\"auto\" \/><\/a><\/li><\/ul><\/div><div class=\"recent-posts-content\"><span class=\"vcard\" style=\"display: none;\"><span class=\"fn\"><a href=\"https:\/\/autism.org\/author\/autismadmin\/\" title=\"Posts by autismAdmin\" rel=\"author\">autismAdmin<\/a><\/span><\/span><span class=\"updated\" style=\"display:none;\">2024-08-07T10:37:37-05:00<\/span><h4 class=\"entry-title\"><a href=\"https:\/\/autism.org\/molecular-and-celluar-mechanisms\/\">The Low-Hanging Fruit: Exploring Monogenic Syndromes with Elevated Rates of Autism<\/a><\/h4><p class=\"meta\"><span class=\"vcard\" style=\"display: none;\"><span class=\"fn\"><a href=\"https:\/\/autism.org\/author\/autismadmin\/\" title=\"Posts by autismAdmin\" rel=\"author\">autismAdmin<\/a><\/span><\/span><span class=\"updated\" style=\"display:none;\">2024-08-07T10:37:37-05:00<\/span><span>July 15th, 2024<\/span><span class=\"fusion-inline-sep\">|<\/span><a href=\"https:\/\/autism.org\/category\/autism-spectrum-disorders\/\" rel=\"category tag\">Autism Spectrum Disorders<\/a>, <a href=\"https:\/\/autism.org\/category\/biomarkers\/\" rel=\"category tag\">Biomarkers<\/a>, <a href=\"https:\/\/autism.org\/category\/webinar\/genetics\/\" rel=\"category tag\">Genetics<\/a>, <a href=\"https:\/\/autism.org\/category\/news\/\" rel=\"category tag\">News<\/a>, <a href=\"https:\/\/autism.org\/category\/autism-spectrum-disorders\/ways-to-help\/\" rel=\"category tag\">Ways to Help<\/a>, <a href=\"https:\/\/autism.org\/webinars\/\" rel=\"category tag\">Webinar<\/a><span class=\"fusion-inline-sep\">|<\/span><\/p><p>   Dr. Daniel Vogt, Ph.D., explores monogenic syndromes and what they can tell us about the underlying causes of autism. He describes signaling pathways critical in early development, highlighting the electrical nature of<\/p><\/div><\/article><article class=\"post fusion-column column col col-lg-4 col-md-4 col-sm-4\"><div class=\"fusion-flexslider fusion-flexslider-loading flexslider flexslider-hover-type-none\"><ul class=\"slides\"><li><a href=\"https:\/\/autism.org\/biomarkers-and-pathophysiology\/\" aria-label=\"Biomarkers start telling us a story: Autism pathophysiology revisited\" class=\"hover-type-none\"><img decoding=\"async\" width=\"700\" height=\"441\" src=\"https:\/\/autism.org\/wp-content\/uploads\/2024\/02\/AdobeStock_209628810-700x441.jpeg\" class=\"attachment-recent-posts size-recent-posts lazyload\" alt=\"Biomarkers DNA image\" srcset=\"data:image\/svg+xml,%3Csvg%20xmlns%3D%27http%3A%2F%2Fwww.w3.org%2F2000%2Fsvg%27%20width%3D%272560%27%20height%3D%271706%27%20viewBox%3D%270%200%202560%201706%27%3E%3Crect%20width%3D%272560%27%20height%3D%271706%27%20fill-opacity%3D%220%22%2F%3E%3C%2Fsvg%3E\" data-orig-src=\"https:\/\/autism.org\/wp-content\/uploads\/2024\/02\/AdobeStock_209628810-700x441.jpeg\" data-srcset=\"https:\/\/autism.org\/wp-content\/uploads\/2024\/02\/AdobeStock_209628810-320x202.jpeg 320w, https:\/\/autism.org\/wp-content\/uploads\/2024\/02\/AdobeStock_209628810-700x441.jpeg 700w\" data-sizes=\"auto\" \/><\/a><\/li><\/ul><\/div><div class=\"recent-posts-content\"><span class=\"vcard\" style=\"display: none;\"><span class=\"fn\"><a href=\"https:\/\/autism.org\/author\/autismadmin\/\" title=\"Posts by autismAdmin\" rel=\"author\">autismAdmin<\/a><\/span><\/span><span class=\"updated\" style=\"display:none;\">2024-09-23T15:39:35-05:00<\/span><h4 class=\"entry-title\"><a href=\"https:\/\/autism.org\/biomarkers-and-pathophysiology\/\">Biomarkers start telling us a story: Autism pathophysiology revisited<\/a><\/h4><p class=\"meta\"><span class=\"vcard\" style=\"display: none;\"><span class=\"fn\"><a href=\"https:\/\/autism.org\/author\/autismadmin\/\" title=\"Posts by autismAdmin\" rel=\"author\">autismAdmin<\/a><\/span><\/span><span class=\"updated\" style=\"display:none;\">2024-09-23T15:39:35-05:00<\/span><span>March 30th, 2024<\/span><span class=\"fusion-inline-sep\">|<\/span><a href=\"https:\/\/autism.org\/category\/biomarkers\/\" rel=\"category tag\">Biomarkers<\/a>, <a href=\"https:\/\/autism.org\/category\/news\/\" rel=\"category tag\">News<\/a>, <a href=\"https:\/\/autism.org\/category\/research\/\" rel=\"category tag\">Research<\/a>, <a href=\"https:\/\/autism.org\/category\/autism-spectrum-disorders\/ways-to-help\/\" rel=\"category tag\">Ways to Help<\/a>, <a href=\"https:\/\/autism.org\/webinars\/\" rel=\"category tag\">Webinar<\/a><span class=\"fusion-inline-sep\">|<\/span><\/p><p>     This is a joint presentation with the World Autism Organisation.  Antonio Persico, MD, a recent ARI Research Grant recipient, explores the role of biomarkers in understanding autism pathophysiology. He<\/p><\/div><\/article><article class=\"post fusion-column column col col-lg-4 col-md-4 col-sm-4\"><div class=\"fusion-flexslider fusion-flexslider-loading flexslider flexslider-hover-type-none\"><ul class=\"slides\"><li><a href=\"https:\/\/autism.org\/gut-autism\/\" aria-label=\"The Gut, Autism, and Mental Health\" class=\"hover-type-none\"><img decoding=\"async\" width=\"700\" height=\"441\" src=\"https:\/\/autism.org\/wp-content\/uploads\/2014\/04\/Untitled-design-31-700x441.jpg\" class=\"attachment-recent-posts size-recent-posts lazyload\" alt=\"Gut Brain Connection Autism\" srcset=\"data:image\/svg+xml,%3Csvg%20xmlns%3D%27http%3A%2F%2Fwww.w3.org%2F2000%2Fsvg%27%20width%3D%271280%27%20height%3D%27720%27%20viewBox%3D%270%200%201280%20720%27%3E%3Crect%20width%3D%271280%27%20height%3D%27720%27%20fill-opacity%3D%220%22%2F%3E%3C%2Fsvg%3E\" data-orig-src=\"https:\/\/autism.org\/wp-content\/uploads\/2014\/04\/Untitled-design-31-700x441.jpg\" data-srcset=\"https:\/\/autism.org\/wp-content\/uploads\/2014\/04\/Untitled-design-31-320x202.jpg 320w, https:\/\/autism.org\/wp-content\/uploads\/2014\/04\/Untitled-design-31-700x441.jpg 700w\" data-sizes=\"auto\" \/><\/a><\/li><\/ul><\/div><div class=\"recent-posts-content\"><span class=\"vcard\" style=\"display: none;\"><span class=\"fn\"><a href=\"https:\/\/autism.org\/author\/autismadmin\/\" title=\"Posts by autismAdmin\" rel=\"author\">autismAdmin<\/a><\/span><\/span><span class=\"updated\" style=\"display:none;\">2024-07-17T09:16:42-05:00<\/span><h4 class=\"entry-title\"><a href=\"https:\/\/autism.org\/gut-autism\/\">The Gut, Autism, and Mental Health<\/a><\/h4><p class=\"meta\"><span class=\"vcard\" style=\"display: none;\"><span class=\"fn\"><a href=\"https:\/\/autism.org\/author\/autismadmin\/\" title=\"Posts by autismAdmin\" rel=\"author\">autismAdmin<\/a><\/span><\/span><span class=\"updated\" style=\"display:none;\">2024-07-17T09:16:42-05:00<\/span><span>March 5th, 2024<\/span><span class=\"fusion-inline-sep\">|<\/span><a href=\"https:\/\/autism.org\/category\/anxiety-2\/\" rel=\"category tag\">Anxiety<\/a>, <a href=\"https:\/\/autism.org\/category\/autism-spectrum-disorders\/\" rel=\"category tag\">Autism Spectrum Disorders<\/a>, <a href=\"https:\/\/autism.org\/category\/webinar\/gastrointestinal-webinar\/\" rel=\"category tag\">Gastrointestinal<\/a>, <a href=\"https:\/\/autism.org\/category\/gastrointestinal\/\" rel=\"category tag\">Gastrointestinal<\/a>, <a href=\"https:\/\/autism.org\/category\/webinar\/immune-issues\/\" rel=\"category tag\">Immune Issues<\/a>, <a href=\"https:\/\/autism.org\/category\/webinar\/neurological\/\" rel=\"category tag\">Neurological<\/a>, <a href=\"https:\/\/autism.org\/category\/autism-spectrum-disorders\/ways-to-help\/\" rel=\"category tag\">Ways to Help<\/a>, <a href=\"https:\/\/autism.org\/webinars\/\" rel=\"category tag\">Webinar<\/a><span class=\"fusion-inline-sep\">|<\/span><\/p><p>    Dr. Calliope Holingue, MPH, Ph.D., provides an overview of the intersection between the gut, autism, and well-being. She outlines recent studies on the GI needs and experiences of autistic individuals and<\/p><\/div><\/article><article class=\"post fusion-column column col col-lg-4 col-md-4 col-sm-4\"><div class=\"fusion-flexslider fusion-flexslider-loading flexslider flexslider-hover-type-none\"><ul class=\"slides\"><li><a href=\"https:\/\/autism.org\/gi-symptoms-2023\/\" aria-label=\"Gastrointestinal Symptoms in Autistic Patients\" class=\"hover-type-none\"><img decoding=\"async\" width=\"400\" height=\"266\" src=\"https:\/\/autism.org\/wp-content\/uploads\/2019\/07\/GI.jpeg\" class=\"attachment-recent-posts size-recent-posts lazyload\" alt=\"The doctor explores the human stomach concept design.\" srcset=\"data:image\/svg+xml,%3Csvg%20xmlns%3D%27http%3A%2F%2Fwww.w3.org%2F2000%2Fsvg%27%20width%3D%27400%27%20height%3D%27266%27%20viewBox%3D%270%200%20400%20266%27%3E%3Crect%20width%3D%27400%27%20height%3D%27266%27%20fill-opacity%3D%220%22%2F%3E%3C%2Fsvg%3E\" data-orig-src=\"https:\/\/autism.org\/wp-content\/uploads\/2019\/07\/GI.jpeg\" data-srcset=\"https:\/\/autism.org\/wp-content\/uploads\/2019\/07\/GI-200x133.jpeg 200w, https:\/\/autism.org\/wp-content\/uploads\/2019\/07\/GI-300x200.jpeg 300w, https:\/\/autism.org\/wp-content\/uploads\/2019\/07\/GI.jpeg 400w\" data-sizes=\"auto\" \/><\/a><\/li><\/ul><\/div><div class=\"recent-posts-content\"><span class=\"vcard\" style=\"display: none;\"><span class=\"fn\"><a href=\"https:\/\/autism.org\/author\/autismadmin\/\" title=\"Posts by autismAdmin\" rel=\"author\">autismAdmin<\/a><\/span><\/span><span class=\"updated\" style=\"display:none;\">2024-09-23T15:43:42-05:00<\/span><h4 class=\"entry-title\"><a href=\"https:\/\/autism.org\/gi-symptoms-2023\/\">Gastrointestinal Symptoms in Autistic Patients<\/a><\/h4><p class=\"meta\"><span class=\"vcard\" style=\"display: none;\"><span class=\"fn\"><a href=\"https:\/\/autism.org\/author\/autismadmin\/\" title=\"Posts by autismAdmin\" rel=\"author\">autismAdmin<\/a><\/span><\/span><span class=\"updated\" style=\"display:none;\">2024-09-23T15:43:42-05:00<\/span><span>March 7th, 2023<\/span><span class=\"fusion-inline-sep\">|<\/span><a href=\"https:\/\/autism.org\/category\/anxiety-2\/\" rel=\"category tag\">Anxiety<\/a>, <a href=\"https:\/\/autism.org\/category\/autism-spectrum-disorders\/\" rel=\"category tag\">Autism Spectrum Disorders<\/a>, <a href=\"https:\/\/autism.org\/category\/gastrointestinal\/\" rel=\"category tag\">Gastrointestinal<\/a>, <a href=\"https:\/\/autism.org\/category\/autism-spectrum-disorders\/ways-to-help\/\" rel=\"category tag\">Ways to Help<\/a>, <a href=\"https:\/\/autism.org\/webinars\/\" rel=\"category tag\">Webinar<\/a><span class=\"fusion-inline-sep\">|<\/span><\/p><p>    This is a joint presentation by the World Autism Organisation and ARI.  Frederico Balzola, MD, discusses the intersection of chronic inflammation, gastrointestinal issues, and autism. He considers intestinal permeability and<\/p><\/div><\/article><article class=\"post fusion-column column col col-lg-4 col-md-4 col-sm-4\"><div class=\"fusion-flexslider fusion-flexslider-loading flexslider flexslider-hover-type-none\"><ul class=\"slides\"><li><a href=\"https:\/\/autism.org\/the-ancient-roots-of-autism-susceptibility-genes\/\" aria-label=\"The Ancient Roots of Autism Susceptibility Genes\" class=\"hover-type-none\"><img decoding=\"async\" width=\"500\" height=\"334\" src=\"https:\/\/autism.org\/wp-content\/uploads\/2019\/01\/genes.jpg\" class=\"attachment-recent-posts size-recent-posts lazyload\" alt=\"Gloved hand removing red gene section from blue model of double helix spiral.\" srcset=\"data:image\/svg+xml,%3Csvg%20xmlns%3D%27http%3A%2F%2Fwww.w3.org%2F2000%2Fsvg%27%20width%3D%27500%27%20height%3D%27334%27%20viewBox%3D%270%200%20500%20334%27%3E%3Crect%20width%3D%27500%27%20height%3D%27334%27%20fill-opacity%3D%220%22%2F%3E%3C%2Fsvg%3E\" data-orig-src=\"https:\/\/autism.org\/wp-content\/uploads\/2019\/01\/genes.jpg\" data-srcset=\"https:\/\/autism.org\/wp-content\/uploads\/2019\/01\/genes-200x134.jpg 200w, https:\/\/autism.org\/wp-content\/uploads\/2019\/01\/genes-300x200.jpg 300w, https:\/\/autism.org\/wp-content\/uploads\/2019\/01\/genes-400x267.jpg 400w, https:\/\/autism.org\/wp-content\/uploads\/2019\/01\/genes.jpg 500w\" data-sizes=\"auto\" \/><\/a><\/li><\/ul><\/div><div class=\"recent-posts-content\"><span class=\"vcard\" style=\"display: none;\"><span class=\"fn\"><a href=\"https:\/\/autism.org\/author\/autismadmin\/\" title=\"Posts by autismAdmin\" rel=\"author\">autismAdmin<\/a><\/span><\/span><span class=\"updated\" style=\"display:none;\">2024-01-22T14:41:37-05:00<\/span><h4 class=\"entry-title\"><a href=\"https:\/\/autism.org\/the-ancient-roots-of-autism-susceptibility-genes\/\">The Ancient Roots of Autism Susceptibility Genes<\/a><\/h4><p class=\"meta\"><span class=\"vcard\" style=\"display: none;\"><span class=\"fn\"><a href=\"https:\/\/autism.org\/author\/autismadmin\/\" title=\"Posts by autismAdmin\" rel=\"author\">autismAdmin<\/a><\/span><\/span><span class=\"updated\" style=\"display:none;\">2024-01-22T14:41:37-05:00<\/span><span>January 31st, 2023<\/span><span class=\"fusion-inline-sep\">|<\/span><a href=\"https:\/\/autism.org\/category\/autism-spectrum-disorders\/\" rel=\"category tag\">Autism Spectrum Disorders<\/a>, <a href=\"https:\/\/autism.org\/category\/webinar\/genetics\/\" rel=\"category tag\">Genetics<\/a>, <a href=\"https:\/\/autism.org\/category\/research\/\" rel=\"category tag\">Research<\/a>, <a href=\"https:\/\/autism.org\/webinars\/\" rel=\"category tag\">Webinar<\/a><span class=\"fusion-inline-sep\">|<\/span><\/p><p>  Casanova dives into the ancient origins of autism susceptibility genes. She outlines periods of rapid gene evolution in early vertebrates and provides an introduction to basic genetics. The presenter characterizes autism genes by<\/p><\/div><\/article><\/section><\/div><div class=\"fusion-clearfix\"><\/div><\/div><\/div><\/div><\/div><\/p>\n","protected":false},"excerpt":{"rendered":"","protected":false},"author":2,"featured_media":5565,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[21,9735,30,20,9475,24],"tags":[4806,9768,3531,9640,3530,9769,9767,9766,9765],"class_list":["post-16972","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-autism-spectrum-disorders","category-biomarkers","category-genetics","category-news","category-ways-to-help","category-webinar","tag-biomarkers","tag-cellular","tag-epigenetics","tag-genes","tag-genetics","tag-inhibitory-neurons","tag-molecular","tag-neurons","tag-pten","webinar-author-daniel-vogt-phd"],"acf":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO Premium plugin v26.6 (Yoast SEO v27.1.1) - 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