Preparation and Mechano-Functional Characterization of PEGylated Fibrin Hydrogels: Impact of Thrombin Concentration.

Three-dimensional (3D) neuronal cultures grown in hydrogels are promising platforms to design brain-like neuronal networks in vitro. However, the optimal properties of such cultures must be tuned to ensure a hydrogel matrix sufficiently porous to promote healthy development but also sufficiently rigid for structural support. Such an optimization is difficult since it implies the exploration of different hydrogel compositions and, at the same time, a functional analysis to validate neuronal culture viability. To advance in this quest, here we present a combination of a rheological protocol and a network-based functional analysis to investigate PEGylated fibrin hydrogel networks with gradually higher stiffness, achieved by increasing the concentration of thrombin. We observed that moderate thrombin concentrations of 10% and 25% in volume shaped healthy networks, although the functional traits depended on the hydrogel stiffness, which was much higher for the latter concentration. Thrombin concentrations of 65% or higher led to networks that did not survive. Our results illustrate the difficulties and limitations in preparing 3D neuronal networks, and stress the importance of combining a mechano-structural characterization of a biomaterial with a functional one.

Connectome-wide structure-function coupling models implicate polysynaptic alterations in autism.

Autism spectrum disorder (ASD) is one of the most common neurodevelopmental diagnoses. Although incompletely understood, structural and functional network alterations are increasingly recognized to be at the core of the condition. We utilized multimodal imaging and connectivity modeling to study structure-function coupling in ASD and probed mono- and polysynaptic mechanisms on structurally-governed network function. We examined multimodal magnetic resonance imaging data in 80 ASD and 61 neurotypical controls from the Autism Brain Imaging Data Exchange (ABIDE) II initiative. We predicted intrinsic functional connectivity from structural connectivity data in each participant using a Riemannian optimization procedure that varies the times that simulated signals can unfold along tractography-derived personalized connectomes. In both ASD and neurotypical controls, we observed improved structure-function prediction at longer diffusion time scales, indicating better modeling of brain function when polysynaptic mechanisms are accounted for. Prediction accuracy differences (∆prediction accuracy) were marked in transmodal association systems, such as the default mode network, in both neurotypical controls and ASD. Differences were, however, lower in ASD in a polysynaptic regime at higher simulated diffusion times. We compared regional differences in ∆prediction accuracy between both groups to assess the impact of polysynaptic communication on structure-function coupling. This analysis revealed that between-group differences in ∆prediction accuracy followed a sensory-to-transmodal cortical hierarchy, with an increased gap between controls and ASD in transmodal compared to sensory/motor systems. Multivariate associative techniques revealed that structure-function differences reflected inter-individual differences in autistic symptoms and verbal as well as non-verbal intelligence. Our network modeling approach sheds light on atypical structure-function coupling in autism, and suggests that polysynaptic network mechanisms are implicated in the condition and that these can help explain its wide range of associated symptoms.

Autism spectrum disorder-specific changes in white matter connectome edge density based on functionally defined nodes.

Introduction: Autism spectrum disorder (ASD) is associated with both functional and microstructural connectome disruptions. We deployed a novel methodology using functionally defined nodes to guide white matter (WM) tractography and identify ASD-related microstructural connectome changes across the lifespan. Methods: We used diffusion tensor imaging and clinical data from four studies in the national database for autism research (NDAR) including 155 infants, 102 toddlers, 230 adolescents, and 96 young adults - of whom 264 (45%) were diagnosed with ASD. We applied cortical nodes from a prior fMRI study identifying regions related to symptom severity scores and used these seeds to construct WM fiber tracts as connectome Edge Density (ED) maps. Resulting ED maps were assessed for between-group differences using voxel-wise and tract-based analysis. We then examined the association of ASD diagnosis with ED driven from functional nodes generated from different sensitivity thresholds. Results: In ED derived from functionally guided tractography, we identified ASD-related changes in infants (pFDR ≤ 0.001-0.483). Overall, more wide-spread ASD-related differences were detectable in ED based on functional nodes with positive symptom correlation than negative correlation to ASD, and stricter thresholds for functional nodes resulted in stronger correlation with ASD among infants (z = -6.413 to 6.666, pFDR ≤ 0.001-0.968). Voxel-wise analysis revealed wide-spread ED reductions in central WM tracts of toddlers, adolescents, and adults. Discussion: We detected early changes of aberrant WM development in infants developing ASD when generating microstructural connectome ED map with cortical nodes defined by functional imaging. These were not evident when applying structurally defined nodes, suggesting that functionally guided DTI-based tractography can help identify early ASD-related WM disruptions between cortical regions exhibiting abnormal connectivity patterns later in life. Furthermore, our results suggest a benefit of involving functionally informed nodes in diffusion imaging-based probabilistic tractography, and underline that different age cohorts can benefit from age- and brain development-adapted image processing protocols.

Early brain microstructural development among preterm infants requiring caesarean section versus those delivered vaginally.

It is known that the rate of caesarean section (C-section) has been increasing among preterm births. However, the relationship between C-section and long-term neurological outcomes is unclear. In this study, we utilized diffusion tensor imaging (DTI) to characterize the association of delivery method with brain white matter (WM) microstructural integrity in preterm infants. We retrospectively analyzed the DTI scans and health records of preterm infants without neuroimaging abnormality on pre-discharge term-equivalent MRI. We applied both voxel-wise and tract-based analyses to evaluate the association between delivery method and DTI metrics across WM tracts while controlling for numerous covariates. We included 68 preterm infants in this study (23 delivered vaginally, 45 delivered via C-section). Voxel-wise and tract-based analyses revealed significantly lower fractional anisotropy values and significantly higher diffusivity values across major WM tracts in preterm infants delivered via C-section when compared to those delivered vaginally. These results may be partially, but not entirely, mediated by lower birth weight among infants delivered by C-section. Nevertheless, these infants may be at risk for delayed neurodevelopment and could benefit from close neurological follow up for early intervention and mitigation of adverse long-term outcomes.

Chemical data evaluation: general considerations and approaches for IUPAC projects and the chemistry community (IUPAC Technical Report).

The International Union of Pure and Applied Chemistry (IUPAC) has a long tradition of supporting the compilation of chemical data and their evaluation through direct projects, nomenclature and terminology work, and partnerships with international scientific bodies, government agencies and other organizations. The IUPAC Interdivisional Subcommittee on Critical Evaluation of Data (ISCED) has been established to provide guidance on issues related to the evaluation of chemical data. In this first report we define the general principles of the evaluation of scientific data and describe best practices and approaches to data evaluation in chemistry.

Dominance of photo over chromatic acclimation strategies by habitat-forming mesophotic red algae.

Red coralline algae are the deepest living macroalgae, capable of creating spatially complex reefs from the intertidal to 100+ m depth with global ecological and biogeochemical significance. How these algae maintain photosynthetic function under increasingly limiting light intensity and spectral availability is key to explaining their large depth distribution. Here, we investigated the photo- and chromatic acclimation and morphological change of free-living red coralline algae towards mesophotic depths in the Fernando do Noronha archipelago, Brazil. From 13 to 86 m depth, thalli tended to become smaller and less complex. We observed a dominance of the photo-acclimatory response, characterized by an increase in photosynthetic efficiency and a decrease in maximum electron transport rate. Chromatic acclimation was generally stable across the euphotic-mesophotic transition with no clear depth trend. Taxonomic comparisons suggest these photosynthetic strategies are conserved to at least the Order level. Light saturation necessitated the use of photoprotection to 65 m depth, while optimal light levels were met at 86 m. Changes to the light environment (e.g. reduced water clarity) due to human activities therefore places these mesophotic algae at risk of light limitation, necessitating the importance of maintaining good water quality for the conservation and protection of mesophotic habitats.

Early brain microstructural development among preterm infants requiring caesarean section versus those delivered vaginally.

It is known that the rate of caesarean section (C-section) has been increasing among preterm births. However, the relationship between C-section and long-term neurological outcomes is unclear. In this study, we utilized diffusion tensor imaging (DTI) to characterize the association of delivery method with brain white matter (WM) microstructural integrity in preterm infants. We retrospectively analyzed the DTI scans and health records of preterm infants without neuroimaging abnormality on pre-discharge term-equivalent MRI. We applied both voxel-wise and tract-based analyses to evaluate the association between delivery method and DTI metrics across WM tracts while controlling for numerous covariates. We included 68 preterm infants in this study (23 delivered vaginally, 45 delivered via C-section). Voxel-wise and tract-based analyses revealed significantly lower fractional anisotropy values and significantly higher diffusivity values across major WM tracts in preterm infants delivered via C-section when compared to those delivered vaginally. These results may be partially, but not entirely, mediated by lower birth weight among infants delivered by C-section. Nevertheless, these infants may be at risk for delayed neurodevelopment and could benefit from close neurological follow up for early intervention and mitigation of adverse long-term outcomes.

Disease-Associated Mutation A554V Disrupts Normal Autoinhibition of DNMT1.

DNA methyltransferase 1 (DNMT1) is the enzyme primarily responsible for propagation of the methylation pattern in cells. Mutations in DNMT1 have been linked to the development of adult-onset neurodegenerative disorders; these disease-associated mutations occur in the regulatory replication foci-targeting sequence (RFTS) domain of the protein. The RFTS domain is an endogenous inhibitor of DNMT1 activity that binds to the active site and prevents DNA binding. Here, we examine the impact of the disease-associated mutation A554V on normal RFTS-mediated inhibition of DNMT1. Wild-type and mutant proteins were expressed and purified to homogeneity for biochemical characterization. The mutation increased DNA binding affinity ~8-fold. In addition, the mutant enzyme exhibited increased DNA methylation activity. Circular dichroism (CD) spectroscopy revealed that the mutation does not significantly impact the secondary structure or relative thermal stability of the isolated RFTS domain. However, the mutation resulted in changes in the CD spectrum in the context of the larger protein; a decrease in relative thermal stability was also observed. Collectively, this evidence suggests that A554V disrupts normal RFTS-mediated autoinhibition of DNMT1, resulting in a hyperactive mutant enzyme. While the disease-associated mutation does not significantly impact the isolated RFTS domain, the mutation results in a weakening of the interdomain stabilizing interactions generating a more open, active conformation of DNMT1. Hyperactive mutant DNMT1 could be responsible for the increased DNA methylation observed in affected individuals.

Rheological Characterization of Three-Dimensional Neuronal Cultures Embedded in PEGylated Fibrin Hydrogels.

Three-dimensional (3D) neuronal cultures are valuable models for studying brain complexity in vitro, and the choice of the bulk material in which the neurons grow is a crucial factor in establishing successful cultures. Indeed, neuronal development and network functionality are influenced by the mechanical properties of the selected material; in turn, these properties may change due to neuron-matrix interactions that alter the microstructure of the material. To advance our understanding of the interplay between neurons and their environment, here we utilized a PEGylated fibrin hydrogel as a scaffold for mouse primary neuronal cultures and carried out a rheological characterization of the scaffold over a three-week period, both with and without cells. We observed that the hydrogels exhibited an elastic response that could be described in terms of the Young's modulus E. The hydrogels without neurons procured a stable E≃420 Pa, while the neuron-laden hydrogels showed a higher E≃590 Pa during the early stages of development that decreased to E≃340 Pa at maturer stages. Our results suggest that neurons and their processes dynamically modify the hydrogel structure during development, potentially compromising both the stability of the material and the functional traits of the developing neuronal network.

Exopolysaccharide Production from Marine-Derived Brevundimonas huaxiensis Obtained from Estremadura Spur Pockmarks Sediments Revealing Potential for Circular Economy.

Marine environments represent an enormous biodiversity reservoir due to their numerous different habitats, being abundant in microorganisms capable of producing biomolecules, namely exopolysaccharides (EPS), with unique physical characteristics and applications in a broad range of industrial sectors. From a total of 67 marine-derived bacteria obtained from marine sediments collected at depths of 200 to 350 m from the Estremadura Spur pockmarks field, off the coast of Continental Portugal, the Brevundimonas huaxiensis strain SPUR-41 was selected to be cultivated in a bioreactor with saline culture media and glucose as a carbon source. The bacterium exhibited the capacity to produce 1.83 g/L of EPS under saline conditions. SPUR-41 EPS was a heteropolysaccharide composed of mannose (62.55% mol), glucose (9.19% mol), rhamnose (19.41% mol), glucuronic acid (4.43% mol), galactose (2.53% mol), and galacturonic acid (1.89% mol). Moreover, SPUR-41 EPS also revealed acyl groups in its composition, namely acetyl, succinyl, and pyruvyl. This study revealed the importance of research on marine environments for the discovery of bacteria that produce new value-added biopolymers for pharmaceutical and other biotechnological applications, enabling us to potentially address saline effluent pollution via a sustainable circular economy.

Impact of postnatal weight gain on brain white matter maturation in very preterm infants.

BACKGROUND AND PURPOSE: Very preterm infants (VPIs, <32 weeks gestational age at birth) are prone to long-term neurological deficits. While the effects of birth weight and postnatal growth on VPIs' neurological outcome are well established, the neurobiological mechanism behind these associations remains elusive. In this study, we utilized diffusion tensor imaging (DTI) to characterize how birth weight and postnatal weight gain influence VPIs' white matter (WM) maturation. METHODS: We included VPIs with complete birth and postnatal weight data in their health record, and DTI scan as part of their predischarge Magnetic Resonance Imaging (MRI). We conducted voxel-wise general linear model and tract-based regression analyses to explore the impact of birth weight and postnatal weight gain on WM maturation. RESULTS: We included 91 VPIs in our analysis. After controlling for gestational age at birth and time between birth and scan, higher birth weight Z-scores were associated with DTI markers of more mature WM tracts, most prominently in the corpus callosum and sagittal striatum. The postnatal weight Z-score changes over the first 4 weeks of life were also associated with increased maturity in these WM tracts, when controlling for gestational age at birth, birth weight Z-score, and time between birth and scan. CONCLUSIONS: In VPIs, birth weight and post-natal weight gain are associated with markers of brain WM maturation, particularly in the corpus callosum, which can be captured on discharge MRI. These neuroimaging metrics can serve as potential biomarkers for the early effects of nutritional interventions on VPIs' brain development.

Efficiency of hematological, enzymological and oxidative stress biomarkers of Cyprinus carpio to an emerging organic compound (alphamethrin) toxicity.

Alphamethrin is one of the extensively used pyrethroids. Its non-specific mode-of-action might affect the non-target-organisms. Its toxicity data on aquatic organisms are lacking. We determined the toxicity (35 days) of alphamethrin (0.6 µg/L and 1.2 µg/L) on non-target-organisms by evaluating the efficiency of hematological, enzymological and antioxidants biomarkers of Cyprinus carpio. Compared with the control group, the efficiency of the biomarkers studied was significantly (p < 0.05) impaired in the alphamethrin treated groups. Alphamethrin-toxicity altered hematology, transaminases and the potency of LDH of fish. ACP and ALP activity and biomarkers of oxidative stress in the gills, liver and muscle tissues were affected. IBRv2 index reveals that the biomarkers were inhibited. The observed impairments were the toxicity effects of alphamethrin with respect to concentration and time. The effectiveness of biomarkers for alphamethrin toxicity was like the toxicity data available on other banned insecticides. Alphamethrin could cause multiorgan toxicity on aquatic organisms at µg/L level.

Association of Body Mass Index and Waist Circumference With Imaging Metrics of Brain Integrity and Functional Connectivity in Children Aged 9 to 10 Years in the US, 2016-2018.

Importance: Aside from widely known cardiovascular implications, higher weight in children may have negative associations with brain microstructure and neurodevelopment. Objective: To evaluate the association of body mass index (BMI) and waist circumference with imaging metrics that approximate brain health. Design, Setting, and Participants: This cross-sectional study used data from the Adolescent Brain Cognitive Development (ABCD) study to examine the association of BMI and waist circumference with multimodal neuroimaging metrics of brain health in cross-sectional and longitudinal analyses over 2 years. From 2016 to 2018, the multicenter ABCD study recruited more than 11 000 demographically representative children aged 9 to 10 years in the US. Children without any history of neurodevelopmental or psychiatric disorders were included in this study, and a subsample of children who completed 2-year follow-up (34%) was included for longitudinal analysis. Exposures: Children's weight, height, waist circumference, age, sex, race and ethnicity, socioeconomic status, handedness, puberty status, and magnetic resonance imaging scanner device were retrieved and included in the analysis. Main Outcomes and Measures: Association of preadolescents' BMI z scores and waist circumference with neuroimaging indicators of brain health: cortical morphometry, resting-state functional connectivity, and white matter microstructure and cytostructure. Results: A total of 4576 children (2208 [48.3%] female) at a mean (SD) age of 10.0 years (7.6 months) were included in the baseline cross-sectional analysis. There were 609 (13.3%) Black, 925 (20.2%) Hispanic, and 2565 (56.1%) White participants. Of those, 1567 had complete 2-year clinical and imaging information at a mean (SD) age of 12.0 years (7.7 months). In cross-sectional analyses at both time points, higher BMI and waist circumference were associated with lower microstructural integrity and neurite density, most pronounced in the corpus callosum (fractional anisotropy for BMI and waist circumference at baseline and second year: P < .001; neurite density for BMI at baseline: P < .001; neurite density for waist circumference at baseline: P = .09; neurite density for BMI at second year: P = .002; neurite density for waist circumference at second year: P = .05), reduced functional connectivity in reward- and control-related networks (eg, within the salience network for BMI and waist circumference at baseline and second year: P < .002), and thinner brain cortex (eg, for the right rostral middle frontal for BMI and waist circumference at baseline and second year: P < .001). In longitudinal analysis, higher baseline BMI was most strongly associated with decelerated interval development of the prefrontal cortex (left rostral middle frontal: P = .003) and microstructure and cytostructure of the corpus callosum (fractional anisotropy: P = .01; neurite density: P = .02). Conclusions and Relevance: In this cross-sectional study, higher BMI and waist circumference among children aged 9 to 10 years were associated with imaging metrics of poorer brain structure and connectivity as well as hindered interval development. Future follow-up data from the ABCD study can reveal long-term neurocognitive implications of excess childhood weight. Imaging metrics that had the strongest association with BMI and waist circumference in this population-level analysis may serve as target biomarkers of brain integrity in future treatment trials of childhood obesity.

Food selectivity and neophobia in children with autism spectrum disorder and neurotypical development: a systematic review.

CONTEXT: Individuals with autism spectrum disorder (ASD) have common eating problems, including food refusal, dietary restrictions, and behavioral problems during eating. OBJECTIVE: The aim of this systematic review was to find more clear evidence on the relationship between food selectivity or food neophobia (FN) and ASD in children up to age 14 years. The PECO-based question was: Are food selectivity and FN behaviors more prevalent in children with ASD than in children with neurotypical development (NTD)?, in which the P is children, E is ASD, C is children with NTD, and O is food selectivity and FN. DATA SOURCES: Clinical studies in the databases PubMed, Embase and Web of Science, comparing children with ASD and those with NTD, were reviewed from October 1966 to October 2021. STUDY SELECTION AND DATA EXTRACTION: A total of 122 studies were analyzed for summary reading, and only 17 of these were included in the descriptive qualitative analysis. In 9 studies, the analysis of food selectivity was performed via a questionnaire. RESULTS: The results showed that children with ASD are more selective than those with NTD. Four studies evaluated FN through scales; however, only 2 found higher levels of FN in the ASD group than in children with NTD. The sensory profile was measured using questionnaires in 9 studies, and we found that altered sensory processing is more common in children with ASD. CONCLUSION: Children with ASD present greater food selectivity than children with NTD. However, the occurrence of FN was higher in only 50% in which FN was investigated, which points to a need for studies that compare FN between siblings with ASD and those with NTD in the same family nucleus. In addition, atypical oral sensitivity seems to be a sensory characteristic most related to eating disorders. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD42021247880.

Connecting Conformational Motions to Rapid Dynamics in Human Purine Nucleoside Phosphorylase.

The influence of protein motions on enzyme catalysis remains a topic of active discussion. Protein motions occur across a variety of time scales, from vibrational fluctuations in femtoseconds, to collective motions in milliseconds. There have been numerous studies that show conformational motions may assist in catalysis, protein folding, and substrate specificity. It is also known through transition path sampling studies that rapid promoting vibrations contribute to enzyme catalysis. Human purine nucleoside phosphorylase (PNP) is one enzyme that contains both an important conformational motion and a rapid promoting vibration. The slower motion in this enzyme is associated with a loop motion, that when open allows substrate entry and product release but closes over the active site during catalysis. We examine the differences between an unconstrained PNP structure and a PNP structure with constraints on the loop motion. To investigate possible coupling between the slow and fast protein dynamics, we employed transition path sampling, reaction coordinate identification, electric field calculations, and free energy calculations reported here.

Mechanical Alloying as a Way to Produce Metastable Single-Phase High-Entropy Alloys beyond the Stability Criteria.

Various stability criteria developed for high-entropy alloys are applied to compositions produced by mechanical alloying. While they agree with the annealed samples, these criteria fail to describe the as-milled metastable systems, highlighting the ability of mechanical alloying to overcome the limitations imposed by these criteria. The criteria are based on atomic size (Ω ≥ 1.1 and δr ≤ 6.6%) and/or electronegativity misfit, as well as on mixing enthalpy (Λ>0.95 J mol-1K-1 and -5 kJ mol-1<∆Hmix<0), or purely thermodynamic (ϕYe>20; ϕKing>1; Teff<500 K). These criteria are applied to several compositions found in the literature and to two metastable fcc solid solutions produced by mechanical alloying with compositions Al0.75CoXFeNi with X = Cr and Mn. Single-phase microstructures are stable up to above 600 K, leading to more stable multiphase systems after annealing above this temperature. Mössbauer spectrometry shows that, whereas the alloy with Cr is paramagnetic in the as-milled and annealed state, the alloy with Mn changes from paramagnetic to ferromagnetic behavior (Curie temperature ~700 K) after annealing. Thermomagnetic experiments on annealed samples show for both compositions some hysteretic events at high temperatures (850 to 1000 K), probably ascribed to reversible ordering phenomena.

Rich dynamics and functional organization on topographically designed neuronal networks in vitro.

Neuronal cultures are a prominent experimental tool to understand complex functional organization in neuronal assemblies. However, neurons grown on flat surfaces exhibit a strongly coherent bursting behavior with limited functionality. To approach the functional richness of naturally formed neuronal circuits, here we studied neuronal networks grown on polydimethylsiloxane (PDMS) topographical patterns shaped as either parallel tracks or square valleys. We followed the evolution of spontaneous activity in these cultures along 20 days in vitro using fluorescence calcium imaging. The networks were characterized by rich spatiotemporal activity patterns that comprised from small regions of the culture to its whole extent. Effective connectivity analysis revealed the emergence of spatially compact functional modules that were associated with both the underpinned topographical features and predominant spatiotemporal activity fronts. Our results show the capacity of spatial constraints to mold activity and functional organization, bringing new opportunities to comprehend the structure-function relationship in living neuronal circuits.

Dynamic and Functional Alterations of Neuronal Networks In Vitro upon Physical Damage: A Proof of Concept.

There is a growing technological interest in combining biological neuronal networks with electronic ones, specifically for biological computation, human-machine interfacing and robotic implants. A major challenge for the development of these technologies is the resilience of the biological networks to physical damage, for instance, when used in harsh environments. To tackle this question, here, we investigated the dynamic and functional alterations of rodent cortical networks grown in vitro that were physically damaged, either by sequentially removing groups of neurons that were central for information flow or by applying an incision that cut the network in half. In both cases, we observed a remarkable capacity of the neuronal cultures to cope with damage, maintaining their activity and even reestablishing lost communication pathways. We also observed-particularly for the cultures cut in half-that a reservoir of healthy neurons surrounding the damaged region could boost resilience by providing stimulation and a communication bridge across disconnected areas. Our results show the remarkable capacity of neuronal cultures to sustain and recover from damage, and may be inspirational for the development of future hybrid biological-electronic systems.

Integrative taxonomy of a new cocculinid limpet dominating the Aurora Vent Field in the central Arctic ocean.

Deep-sea hydrothermal vents host lush chemosynthetic communities, dominated by endemic fauna that cannot live in other ecosystems. Despite over 500 active vents found worldwide, the Arctic has remained a little-studied piece of vent biogeography. Though located as early as 2001, the faunal communities of the Aurora Vent Field on the ultra-slow spreading Gakkel Ridge remained unsampled until recently, owing to difficulties with sampling on complex topography below permanent ice. Here, we report an unusual cocculinid limpet abundant on inactive chimneys in Aurora (3883-3884 m depth), describing it as Cocculina aurora n. sp. using an integrative approach combining traditional dissection, electron microscopy, molecular phylogeny, and three-dimensional anatomical reconstruction. Gross anatomy of the new species was typical for Cocculina, but it has a unique radula with broad, multi-cuspid rachidian where the outermost lateral is reduced compared to typical cocculinids. A phylogenetic reconstruction using the mitochondrial COI gene also confirmed its placement in Cocculina. Only the second cocculinid found at vents following the description of the Antarctic Cocculina enigmadonta, this is currently the sole cocculinid restricted to vents. Our discovery adds to the evidence that Arctic vents host animal communities closely associated with wood falls and distinct from other parts of the world.

Age-dependent white matter microstructural disintegrity in autism spectrum disorder.

There has been increasing evidence of White Matter (WM) microstructural disintegrity and connectome disruption in Autism Spectrum Disorder (ASD). We evaluated the effects of age on WM microstructure by examining Diffusion Tensor Imaging (DTI) metrics and connectome Edge Density (ED) in a large dataset of ASD and control patients from different age cohorts. N = 583 subjects from four studies from the National Database of Autism Research were included, representing four different age groups: (1) A Longitudinal MRI Study of Infants at Risk of Autism [infants, median age: 7 (interquartile range 1) months, n = 155], (2) Biomarkers of Autism at 12 months [toddlers, 32 (11)m, n = 102], (3) Multimodal Developmental Neurogenetics of Females with ASD [adolescents, 13.1 (5.3) years, n = 230], (4) Atypical Late Neurodevelopment in Autism [young adults, 19.1 (10.7)y, n = 96]. For each subject, we created Fractional Anisotropy (FA), Mean- (MD), Radial- (RD), and Axial Diffusivity (AD) maps as well as ED maps. We performed voxel-wise and tract-based analyses to assess the effects of age, ASD diagnosis and sex on DTI metrics and connectome ED. We also optimized, trained, tested, and validated different combinations of machine learning classifiers and dimensionality reduction algorithms for prediction of ASD diagnoses based on tract-based DTI and ED metrics. There is an age-dependent increase in FA and a decline in MD and RD across WM tracts in all four age cohorts, as well as an ED increase in toddlers and adolescents. After correction for age and sex, we found an ASD-related decrease in FA and ED only in adolescents and young adults, but not in infants or toddlers. While DTI abnormalities were mostly limited to the corpus callosum, connectomes showed a more widespread ASD-related decrease in ED. Finally, the best performing machine-leaning classification model achieved an area under the receiver operating curve of 0.70 in an independent validation cohort. Our results suggest that ASD-related WM microstructural disintegrity becomes evident in adolescents and young adults-but not in infants and toddlers. The ASD-related decrease in ED demonstrates a more widespread involvement of the connectome than DTI metrics, with the most striking differences being localized in the corpus callosum.