Does the loss of diadromy imply the loss of salinity tolerance? A gene expression study with replicate nondiadromous populations of Galaxias maculatus.

The recurrent colonization of freshwater habitats and subsequent loss of diadromy is a major ecological transition that has been reported in many ancestrally diadromous fishes. Such residency is often accompanied by a loss of tolerance to seawater. The amphidromous Galaxias maculatus has repeatedly colonized freshwater streams with evidence that freshwater-resident populations exhibit stark differences in their tolerance to higher salinities. Here, we used transcriptomics to gain insight into the mechanisms contributing to reduced tolerance to higher salinities in freshwater resident populations. We conducted an acute salinity challenge (0 ppt to 23-25 ppt) and measured osmoregulatory ability (muscle water content) over 48 h in three populations: diadromous, saltwater intolerant resident (Toltén), and saltwater tolerant resident (Valdivia). RNA sequencing of the gills identified genes that were differentially expressed in association with the salinity change and associated with the loss of saltwater tolerance in the Toltén population. Key genes associated with saltwater acclimation were characterized in diadromous G. maculatus individuals, some of which were also expressed in the saltwater tolerant resident population (Valdivia). We found that some of these "saltwater acclimation" genes, including the cystic fibrosis transmembrane conductance regulator gene (CFTR), were not significantly upregulated in the saltwater intolerant resident population (Toltén), suggesting a potential mechanism for the loss of tolerance to higher salinities. As the suite of differentially expressed genes in the diadromous-resident comparison differed between freshwater populations, we hypothesize that diadromy loss results in unique evolutionary trajectories due to drift, so the loss of diadromy does not necessarily lead to a loss in upper salinity tolerance.

La colonización recurrente de hábitats de agua dulce y la subsecuente pérdida de diadromía es una transición ecológica importante que ha sido reportada en varias especies de peces con ancestros diádromos. Esta residencia está acompañada frecuentemente por la pérdida de tolerancia a ambientes de agua salada. Galaxias maculatus, especie anfídroma, ha colonizado ríos repetidamente y existe evidencia que las poblaciones residentes presentan diferencias respecto a la tolerancia al agua salada. En este estudio, usamos transcriptómica para dilucidar los mecanismos que contribuyen a la reducida tolerancia a altas salinidades en las poblaciones residentes de agua dulce. Realizamos un desafío agudo de salinidad (0 ppt a 23-2 ppt) y medimos la habilidad osmoreguladora (contenido de agua en músculo) por 48 horas en individuos de tres poblaciones: una diádroma, una intolerante a agua salada (Toltén) y una tolerante a agua salada (Valdivia). Con el secuenciamiento de ARN de las branquias identificamos los genes expresados diferencialmente al cambio de salinidad y cuales están asociados a la pérdida de tolerancia a agua salada en la población de Toltén. Genes claves asociados a la aclimatación al agua salada fueron caracterizados en individuos diádromos, algunos de ellos también se expresaron en la población residente tolerante al agua salada (Valdivia). Sin embargo, algunos genes involucrados en la aclimatación al agua salada, incluyendo el gen regulador de la conductancia transmembrana de la fibrosis quística (CFTR), no se diferenciaron significativamente en la población residente intolerante al agua salada (Toltén), sugiriendo un mecanismo potencial de la pérdida de tolerancia a ambientes con salinidad elevada. Como el conjunto de genes expresados difiere entre las dos poblaciones residentes al compararse con la población diádroma, hipotetizamos que la pérdida de diadromía resulta en trayectorias evolutivas únicas debido a deriva génica, por lo que la pérdida de la diadromía no necesariamente conlleva a la pérdida de la tolerancia a aguas saladas.

Digital Classification of Chilean Pelagic Species in Fishing Landing Lines.

Fishing landings in Chile are inspected to control fisheries that are subject to catch quotas. The control process is not easy since the volumes extracted are large and the numbers of landings and artisan shipowners are high. Moreover, the number of inspectors is limited, and a non-automated method is utilized that normally requires months of training. In this work, we propose, design, and implement an automated fish landing control system. The system consists of a custom gate with a camera array and controlled illumination that performs automatic video acquisition once the fish landing starts. The imagery is sent to the cloud in real time and processed by a custom-designed detection algorithm based on deep convolutional networks. The detection algorithm identifies and classifies different pelagic species in real time, and it has been tuned to identify the specific species found in landings of two fishing industries in the Biobío region in Chile. A web-based industrial software was also developed to display a list of fish detections, record relevant statistical summaries, and create landing reports in a user interface. All the records are stored in the cloud for future analyses and possible Chilean government audits. The system can automatically, remotely, and continuously identify and classify the following species: anchovy, jack mackerel, jumbo squid, mackerel, sardine, and snoek, considerably outperforming the current manual procedure.

A Spatial-Spectral Classification Method Based on Deep Learning for Controlling Pelagic Fish Landings in Chile.

Fishing has provided mankind with a protein-rich source of food and labor, allowing for the development of an important industry, which has led to the overexploitation of most targeted fish species. The sustainable management of these natural resources requires effective control of fish landings and, therefore, an accurate calculation of fishing quotas. This work proposes a deep learning-based spatial-spectral method to classify five pelagic species of interest for the Chilean fishing industry, including the targeted Engraulis ringens, Merluccius gayi, and Strangomera bentincki and non-targeted Normanichthtys crockeri and Stromateus stellatus fish species. This proof-of-concept method is composed of two channels of a convolutional neural network (CNN) architecture that processes the Red-Green-Blue (RGB) images and the visible and near-infrared (VIS-NIR) reflectance spectra of each species. The classification results of the CNN model achieved over 94% in all performance metrics, outperforming other state-of-the-art techniques. These results support the potential use of the proposed method to automatically monitor fish landings and, therefore, ensure compliance with the established fishing quotas.

Body mass and cell size shape the tolerance of fishes to low oxygen in a temperature-dependent manner.

Aerobic metabolism generates 15-20 times more energy (ATP) than anaerobic metabolism, which is crucial in maintaining energy budgets in animals, fueling metabolism, activity, growth and reproduction. For ectothermic water-breathers such as fishes, low dissolved oxygen may limit oxygen uptake and hence aerobic metabolism. Here, we assess, within a phylogenetic context, how abiotic and biotic drivers explain the variation in hypoxia tolerance observed in fishes. To do so, we assembled a database of hypoxia tolerance, measured as critical oxygen tensions (Pcrit ) for 195 fish species. Overall, we found that hypoxia tolerance has a clear phylogenetic signal and is further modulated by temperature, body mass, cell size, salinity and metabolic rate. Marine fishes were more susceptible to hypoxia than freshwater fishes. This pattern is consistent with greater fluctuations in oxygen and temperature in freshwater habitats. Fishes with higher oxygen requirements (e.g. a high metabolic rate relative to body mass) also were more susceptible to hypoxia. We also found evidence that hypoxia and warming can act synergistically, as hypoxia tolerance was generally lower in warmer waters. However, we found significant interactions between temperature and the body and cell size of a fish. Constraints in oxygen uptake related to cellular surface area to volume ratios and effects of viscosity on the thickness of the boundary layers enveloping the gills could explain these thermal dependencies. The lower hypoxia tolerance in warmer waters was particularly pronounced for fishes with larger bodies and larger cell sizes. Previous studies have found a wide diversity in the direction and strength of relationships between Pcrit and body mass. By including interactions with temperature, our study may help resolve these divergent findings, explaining the size dependency of hypoxia tolerance in fish.

Microplastic concentration, distribution and dynamics along one of the largest Mediterranean-climate rivers: A whole watershed approach.

Microplastics (MPs) have been recognized as one of the most ubiquitous environmental pollutants globally. They have been found in all ecosystems studied to date, threatening biological diversity, ecosystem functioning and human health. The present study aimed to elucidate the environmental and anthropogenic drivers of MP dynamics in the whole catchment of the Biobío river, one of the largest rivers in South America. MP concentration and characteristics were analysed in 18 sites subjected to different sources of pollution and other human-related impacts. The sampling sites were classified in relation to altitudinal zones (highland, midland and lowland) and ecosystem types (fluvial and reservoir), and different water and territorial environmental variables were further collated and considered for analysis. Seven types of microplastic polymers were identified in the samples analysed, with a catchment mean (±SE) MP concentration of 22 ± 0.4 particles m-3, and MP presence being significantly higher in lowlands (26 ± 2 particle m-3) and in reservoirs (42 ± 14 particle m-3). The most abundant type of MP was fragments (84%), with a mean concentration of 37 ± 6 particles m-3. Overall, MP concentrations were low compared to those found in other studies, with a strong influence of human population size.

Genomic basis of the loss of diadromy in Galaxias maculatus: Insights from reciprocal transplant experiments.

Diadromy is known for having major effects on the distribution and richness of aquatic species, and so does its loss. The loss of diadromy has led to the diversification of many species, yet research focusing on understanding its molecular basis and consequences are limited. This is particularly true for amphidromous species despite being the most abundant group of diadromous species. Galaxias maculatus, an amphidromous species and one of the most widely distributed fishes in the Southern Hemisphere, exhibits many instances of nonmigratory or resident populations. The existence of naturally replicated resident populations in Patagonia can serve as an ideal system for the study of the mechanisms that lead to the loss of the diadromy and its ecological and evolutionary consequences. Here, we studied two adjacent river systems in which resident populations are genetically differentiated yet derived from the same diadromous population. By combining a reciprocal transplant experiment with genomic data, we showed that the two resident populations followed different evolutionary pathways by exhibiting a differential response in their capacity to survive in salt water. While one resident population was able to survive salt water, the other was not. Genomic analyses provided insights into the genes that distinguished (a) migratory from nonmigratory populations; (b) populations that can vs those that cannot survive a saltwater environment; and (c) between these resident populations. This study demonstrates that the loss of diadromy can be achieved by different pathways and that environmental (selection) and random (genetic drift) forces shape this dynamic evolutionary process.

Randomized controlled trial of vitamin D supplementation in children with autism spectrum disorder.

BACKGROUND: Autism spectrum disorder (ASD) is a frequent developmental disorder characterized by pervasive deficits in social interaction, impairment in verbal and nonverbal communication, and stereotyped patterns of interests and activities. It has been previously reported that there is vitamin D deficiency in autistic children; however, there is a lack of randomized controlled trials of vitamin D supplementation in ASD children. METHODS: This study is a double-blinded, randomized clinical trial (RCT) that was conducted on 109 children with ASD (85 boys and 24 girls; aged 3-10 years). The aim of this study was to assess the effects of vitamin D supplementation on the core symptoms of autism in children. ASD patients were randomized to receive vitamin D3 or placebo for 4 months. The serum levels of 25-hydroxycholecalciferol (25 (OH)D) were measured at the beginning and at the end of the study. The autism severity and social maturity of the children were assessed by the Childhood Autism Rating Scale (CARS), Aberrant Behavior Checklist (ABC), Social Responsiveness Scale (SRS), and the Autism Treatment Evaluation Checklist (ATEC). TRIAL REGISTRATION NUMBER: UMIN-CTR Study Design: trial number: UMIN000020281. RESULTS: Supplementation of vitamin D was well tolerated by the ASD children. The daily doses used in the therapy group was 300 IU vitamin D3/kg/day, not to exceed 5,000 IU/day. The autism symptoms of the children improved significantly, following 4-month vitamin D3 supplementation, but not in the placebo group. This study demonstrates the efficacy and tolerability of high doses of vitamin D3 in children with ASD. CONCLUSIONS: This study is the first double-blinded RCT proving the efficacy of vitamin D3 in ASD patients. Depending on the parameters measured in the study, oral vitamin D supplementation may safely improve signs and symptoms of ASD and could be recommended for children with ASD. At this stage, this study is a single RCT with a small number of patients, and a great deal of additional wide-scale studies are needed to critically validate the efficacy of vitamin D in ASD.

Relationship between absolute and relative ratios of glutamate, glutamine and GABA and severity of autism spectrum disorder.

Autism spectrum disorder (ASD) is a neurodevelopmental pathology characterized by an impairment in social interaction, communication difficulties, and repetitive behaviors. Glutamate signaling abnormalities are thought to be considered as major etiological mechanisms leading to ASD. The search for amino-acidic catabolytes related to glutamate in patients with different levels of ASD might help current research to clarify the mechanisms underlying glutamate signaling and its disorders, particularly in relation to ASD. In the present study, plasma levels of the amino acids and their derivatives glutamate, glutamine, and γ-aminobutyric acid (GABA), associated with their relative ratios, were evaluated using an enzyme-linked immunosorbent assay (ELISA) technique in 40 male children with ASD and in 38 age- and gender-matched neurotypical health controls. The Social Responsiveness Scale (SRS) was used to evaluate social cognition, and the Childhood Autism Rating Scale (CARS) was used to assess subjects' behaviors. Children with ASD exhibited a significant elevation of plasma GABA and glutamate/glutamine ratio, as well as significantly lower levels of plasma glutamine and glutamate/GABA ratios compared to controls. No significant correlation was found between glutamate levels and the severity of autism, measured by CARS and SRS. In receiver operating characteristic (ROC) curve analysis, the area under the curve for GABA compared to other parameters was close to one, indicating its potential use as a biomarker. Glutamine appeared as the best predictive prognostic markers in the present study. The results of the present study indicate a disturbed balance between GABAergic and glutamatergic neurotransmission in ASD. The study also indicates that an increased plasma level of GABA can be potentially used as an early diagnostic biomarker for ASD.

Effects of arsenic toxicity beyond epigenetic modifications.

Worldwide chronic arsenic (As) poisoning by arsenic-contaminated groundwater is one of the most threatening public health problems. Chronic inorganic As (inAs) exposure has been associated with various forms of cancers and numerous other pathological effects in humans, collectively known as arsenicosis. Over the past decade, evidence indicated that As-induced epigenetic modifications have a role in the adverse effects on human health. The main objective of this article is to review the evidence on epigenetic modifications induced by arsenicals. The epigenetic components play a crucial role in the regulation of gene expression, at both transcriptional and posttranscriptional levels. We synthesized the large body of existing research on arsenic exposure and epigenetic mechanisms of health outcomes with an emphasis on recent publications. Changes in patterns of DNA methylation, histone posttranslational modifications, and microRNAs have been repeatedly observed after inAs exposure in laboratory studies and in studies of human populations. Such alterations have the potential to disturb cellular homeostasis, resulting in the modulation of key pathways in the As-induced carcinogenesis. The present article reviews recent data on As-induced epigenetic effects and concludes that it is time for heightened awareness of pathogenic arsenic exposure, particularly for pregnant women and children, given the potential for a long-lasting disturbed cellular homeostasis.

Fluctuating seawater pH/pCO2 regimes are more energetically expensive than static pH/pCO2 levels in the mussel Mytilus edulis.

Ocean acidification (OA) studies typically use stable open-ocean pH or CO2 values. However, species living within dynamic coastal environments can naturally experience wide fluctuations in abiotic factors, suggesting their responses to stable pH conditions may not be reflective of either present or near-future conditions. Here we investigate the physiological responses of the mussel Mytilus edulis to variable seawater pH conditions over short- (6 h) and medium-term (2 weeks) exposures under both current and near-future OA scenarios. Mussel haemolymph pH closely mirrored that of seawater pH over short-term changes of 1 pH unit with acidosis or recovery accordingly, highlighting a limited capacity for acid-base regulation. After 2 weeks, mussels under variable pH conditions had significantly higher metabolic rates, antioxidant enzyme activities and lipid peroxidation than those exposed to static pH under both current and near-future OA scenarios. Static near-future pH conditions induced significant acid-base disturbances and lipid peroxidation compared with the static present-day conditions but did not affect the metabolic rate. These results clearly demonstrate that living in naturally variable environments is energetically more expensive than living in static seawater conditions, which has consequences for how we extrapolate future OA responses in coastal species.

Lessons from two high CO2 worlds - future oceans and intensive aquaculture.

Exponentially rising CO2 (currently ~400 µatm) is driving climate change and causing acidification of both marine and freshwater environments. Physiologists have long known that CO2 directly affects acid-base and ion regulation, respiratory function and aerobic performance in aquatic animals. More recently, many studies have demonstrated that elevated CO2 projected for end of this century (e.g. 800-1000 µatm) can also impact physiology, and have substantial effects on behaviours linked to sensory stimuli (smell, hearing and vision) both having negative implications for fitness and survival. In contrast, the aquaculture industry was farming aquatic animals at CO2 levels that far exceed end-of-century climate change projections (sometimes >10 000 µatm) long before the term 'ocean acidification' was coined, with limited detrimental effects reported. It is therefore vital to understand the reasons behind this apparent discrepancy. Potential explanations include 1) the use of 'control' CO2 levels in aquaculture studies that go beyond 2100 projections in an ocean acidification context; 2) the relatively benign environment in aquaculture (abundant food, disease protection, absence of predators) compared to the wild; 3) aquaculture species having been chosen due to their natural tolerance to the intensive conditions, including CO2 levels; or 4) the breeding of species within intensive aquaculture having further selected traits that confer tolerance to elevated CO2 . We highlight this issue and outline the insights that climate change and aquaculture science can offer for both marine and freshwater settings. Integrating these two fields will stimulate discussion on the direction of future cross-disciplinary research. In doing so, this article aimed to optimize future research efforts and elucidate effective mitigation strategies for managing the negative impacts of elevated CO2 on future aquatic ecosystems and the sustainability of fish and shellfish aquaculture.

Does sex really matter? Explaining intraspecies variation in ocean acidification responses.

Ocean acidification (OA) poses a major threat to marine ecosystems globally, having significant ecological and economic importance. The number and complexity of experiments examining the effects of OA has substantially increased over the past decade, in an attempt to address multi-stressor interactions and long-term responses in an increasing range of aquatic organisms. However, differences in the response of males and females to elevated pCO2 have been investigated in fewer than 4% of studies to date, often being precluded by the difficulty of determining sex non-destructively, particularly in early life stages. Here we highlight that sex can significantly impact organism responses to OA, differentially affecting physiology, reproduction, biochemistry and ultimately survival. What is more, these impacts do not always conform to ecological theory based on differential resource allocation towards reproduction, which would predict females to be more sensitive to OA owing to the higher production cost of eggs compared with sperm. Therefore, non-sex-specific studies may overlook subtle but ecologically significant differences in the responses of males and females to OA, with consequences for forecasting the fate of natural populations in a near-future ocean.

Ecophysiological adaptations to variable salinity environments in the crab Hemigrapsus crenulatus from the Southeastern Pacific coast: Sodium regulation, respiration and excretion.

The estuarine crab Hemigrapsus crenulatus is a key benthic species of estuarine and intertidal ecosystems of the South Pacific, habitats that experience wide fluctuations in salinity. The physiological strategies that allow this crab to thrive under variable salinities, and how they change during the benthic stages of their life cycle, were evaluated under laboratory conditions. Oxygen consumption, ammonia excretion and the regulatory capacity of Na+ through the normal range of environmental salinities (i.e. 5, 10, 15, 20, 25, 30) were evaluated in three size classes, ranging from juveniles to adults. In all sizes, the oxygen consumption, ammonia excretion and regulatory capacity of Na+ decreased as salinity increased, with the highest values at 5 and the lowest values at 30 salinity. Bigger crabs showed a higher capacity to regulate Na+, as well as higher respiration and excretion rates compared to smaller crabs, suggesting that they are better equipped to exploit areas of the estuary with low salinity. Regardless of its size, H. crenulatus is a strong hyper regulator in diluted media (i.e. 5-20) while a conformer at salinities higher than 20. The regulatory capacity of Na+ was positively related with oxygen consumption and ammonia excretion rates. These relationships between sodium regulation, respiration and excretion are interpreted as adaptive physiological mechanisms that allow H. crenulatus to maintain the osmotic and bioenergetic balance over a wide range of environmental salinities.

Tide-related biological rhythm in the oxygen consumption rate of ghost shrimp (Neotrypaea uncinata).

The effects of tidal height (high and low), acclimation to laboratory conditions (days in captivity) and oxygen level (hypoxia and normoxia) were evaluated in the oxygen consumption rate (OCR) of the ghost shrimp Neotrypaea uncinata We evaluated the hypothesis that N. uncinata reduces its OCR during low tide and increases it during high tide, regardless of oxygen level or acclimation. Additionally, the existence of an endogenous rhythm in OCR was explored, and we examined whether it synchronized with tidal, diurnal or semidiurnal cycles. Unexpectedly, high OCRs were observed at low tide, during normoxia, in non-acclimated animals. Results from a second, longer experiment under normoxic conditions suggested the presence of a tide-related metabolic rhythm, a response pattern not yet demonstrated for a burrowing decapod. Although rhythms persisted for only 2 days after capture, their period of 12.8 h closely matched the semidiurnal tidal cycle that ghost shrimp confront inside their burrows.

Fluoxetine Exhibits Pharmacological Effects and Trait-Based Sensitivity in a Marine Worm.

Global production of pharmacologically active compounds exceeds 100 000 tons annually, a proportion of which enters aquatic environments through patient use, improper medicine disposal, and production. These compounds are designed to have mode-of-action (MoA) effects on specific biological pathways, with potential to impact nontarget species. Here, we used MoA and trait-based approaches to quantify uptake and biological effects of fluoxetine, a selective serotonin reuptake inhibitor, in filter and deposit feeding marine worms (Hediste diversicolor). Worms exposed to 10 µg L(-1), accumulated fluoxetine with a body burden over 270 times greater than exposure concentrations, resulting in ∼10% increased coelomic fluid serotonin, a pharmacological effect. Observed effects included weight loss (up to 2% at 500 µg L(-1)), decreased feeding rate (68% at 500 µg L(-1)), and altered metabolism (oxygen consumption, ammonia excretion, and O/N from 10 µg L(-1)). Bioconcentration of fluoxetine was dependent on route of uptake, with filter feeding worms experiencing up to 130 times greater body burden ratios and increased magnitudes of effects than deposit feeders, a trait-based sensitivity likely as a consequence of fluoxetine partitioning to sediment. This study highlights how novel approaches such as MoA and trait-based methods can supplement environmental risk assessments of pharmaceuticals.

Effect of Microplastic on the Gills of the Shore Crab Carcinus maenas.

Microscopic plastic debris (microplastics, <5 mm in diameter) is ubiquitous in the marine environment. Previous work has shown that microplastics may be ingested and inhaled by the shore crab Carcinus maenas, although the biological consequences are unknown. Here, we show that acute aqueous exposure to polystyrene microspheres (8 µm) with different surface coatings had significant but transient effects on branchial function. Microspheres inhaled into the gill chamber had a small but significant dose-dependent effect on oxygen consumption after 1 h of exposure, returning to normal levels after 16 h. Ion exchange was also affected, with a small but significant decrease in hemolymph sodium ions and an increase in calcium ions after 24 h post-exposure. To further asses the effects on osmoregulation, we challenged crabs with reduced salinity after microplastic exposure. Neither microspheres nor natural sediments altered the crab's response to osmotic stress regardless of plastic concentration added. Carboxylated (COOH) and aminated (NH2) polystyrene microspheres were distributed differently across the gill surface, although neither had a significant adverse impact on gill function. These results illustrate the extent of the physiological effects of microplastics compared to the physiological resilience of shore crabs in maintaining osmoregulatory and respiratory function after acute exposure to both anthropogenic plastics and natural particles.

The levels of blood mercury and inflammatory-related neuropeptides in the serum are correlated in children with autism spectrum disorder.

Tachykinins (substance P, neurokinin A, and neurokinin B) are pro-inflammatory neuropeptides that may play an important role in some autoimmune neuroinflammatory diseases, including autism spectrum disorder (ASD). Mercury (Hg) is a neurotoxicant, and potentially one of the main environmental triggers for ASD as it induces neuroinflammation with a subsequent release of neuropeptides. This is the first study to explore the potentially causal relationship between levels of serum neurokinin A and blood mercury (BHg) in children with ASD. Levels of serum neurokinin A and BHg were measured in 84 children with ASD, aged between 3 and 10 years, and 84 healthy-matched children. There was a positive linear relationship between the Childhood Autism Rating Scale (CARS) and both serum neurokinin A and BHg. ASD children had significantly higher levels of serum neurokinin A than healthy controls (P < 0.001). Increased levels of serum neurokinin A and BHg were respectively found in 54.8 % and 42.9 % of the two groups. There was significant and positive linear relationship between levels of serum neurokinin A and BHg in children with moderate and severe ASD, but not in healthy control children. It was found that 78.3 % of the ASD patients with increased serum levels of neurokinin A had elevated BHg levels (P < 0.001). Neuroinflammation, with increased levels of neurokinin A, is seen in some children with ASD, and may be caused by elevated BHg levels. Further research is recommended to determine the pathogenic role of increased levels of serum neurokinin A and BHg in ASD. The therapeutic role of tachykinin receptor antagonists, a potential new class of anti-inflammatory medications, and Hg chelators, should also be studied in ASD.

Acid glycosaminoglycan (aGAG) excretion is increased in children with autism spectrum disorder, and it can be controlled by diet.

Autism research continues to receive considerable attention as the options for successful management are limited. The understanding of the autism spectrum disorder (ASD) etiology has now progressed to encompass genetic, epigenetic, neurological, hormonal, and environmental factors that affect outcomes for patients with ASD. Glycosaminoglycans (GAGs) are a family of linear, sulfated polysaccharides that are associated with central nervous system (CNS) development, maintenance, and disorders. Proteoglycans (PG) regulate diverse functions in the central nervous system. Heparan sulfate (HS) and chondroitin sulfate (CS) are two major GAGs present in the PGs of the CNS. As neuroscience advances, biochemical treatments to correct brain chemistry become better defined. Nutrient therapy can be very potent and has minimal to no side effects, since no molecules foreign to the body are needed. Given GAGs are involved in several neurological functions, and that its level can be somewhat modulated by the diet, the present study aimed to evaluate the role of GAGs levels in ASD symptoms. Both tGAG and its different fractions were evaluated in the urine of ASD and healthy control childrens. As levels differed between groups, a second trial was conduted evaluating if diet could reduce tGAG levels and if this in turn decrease ASD symptoms. The present study found that tGAG concentration was significantly higher in the urine of children with ASD compared to healthy control children and this was also evident in all GAG fractions. Within groups (controls and ASD), no gender differences in GAG excretion were found. The use of a 90 days elimination diet (casein-free, special carbohydrates, multivitamin/mineral supplement), had major effects in reducing urinary tGAG excretion in children with ASD.

The positive association between elevated blood lead levels and brain-specific autoantibodies in autistic children from low lead-polluted areas.

The underlying pathogenic mechanism in autoimmune disorders is the formation of autoantibodies. In children with autism spectrum disorder (ASD), it has been documented increased levels of brain-specific autoantibodies. Furthermore, lead (Pb) has been identified as one of the main neurotoxicants acting as environmental triggers for ASD as it induces neuroinflammation and autoimmunity. The present study is the first to explore a potential relationship between the levels of blood lead (BPb) and seropositivity of anti-ribosomal P protein antibodies in ASD children. Levels of BPb and serum anti-ribosomal P protein antibodies were measured in 60 children with ASD and 60 healthy control matched children, aged between 5 and 12 years, recruited from low Pb-polluted areas. The levels of BPb were significantly higher in ASD children than in healthy control children (P < 0.001). Patients with ASD had significantly higher frequency of increased BPb levels ≥10 µg/dL (43.3 %) than healthy control children (13.3 %; P < 0.001). There were significant and positive correlations between the levels of BPb, and the values of Childhood Autism Rating Scale (CARS) (P < 0.01) and IQ in children with ASD (P < 0.001). Patients with ASD showing increased levels of BPb had significantly higher frequency of seropositivity of anti-ribosomal P antibodies (92.3 %) than patients with normal BPb levels (32.3 %; P < 0.001). The findings of the present study suggest that increased levels of BPb in some children with ASD may trigger the production of serum anti-ribosomal P antibodies. Further research is warranted to determine if the production of brain autoantibodies is triggered by environmental Pb exposure in children with ASD. The possible therapeutic role of Pb chelators in ASD children should also be studied.