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Abstract Background Autism comprises a spectrum of behavioral and cognitive disturbances of childhood development and is known to be highly heritable. Although numerous approaches have been used to identify genes implicated in the development of autism, less than 10% of autism cases have been attributed to single gene disorders. Methods We describe the use of high-resolution genome-wide tilepath microarrays and comparative genomic hybridization to identify copy number variants within 119 probands from multiplex autism families. We next carried out DNA methylation analysis by bisulfite sequencing in a proband and his family, expanding this analysis to methylation analysis of peripheral blood and temporal cortex DNA of autism cases and matched controls from independent datasets. We also assessed oxytocin receptor (OXTR) gene expression within the temporal cortex tissue by quantitative real-time polymerase chain reaction (PCR). Results Our analysis revealed a genomic deletion containing the oxytocin receptor gene, OXTR (MIM accession no.: 167055), previously implicated in autism, was present in an autism proband and his mother who exhibits symptoms of obsessive-compulsive disorder. The proband's affected sibling did not harbor this deletion but instead may exhibit epigenetic misregulation of this gene through aberrant gene silencing by DNA methylation. Further DNA methylation analysis of the CpG island known to regulate OXTR expression identified several CpG dinucleotides that show independent statistically significant increases in the DNA methylation status in the peripheral blood cells and temporal cortex in independent datasets of individuals with autism as compared to control samples. Associated with the increase in methylation of these CpG dinucleotides is our finding that OXTR mRNA showed decreased expression in the temporal cortex tissue of autism cases matched for age and sex compared to controls. Conclusion Together, these data provide further evidence for the role of OXTR and the oxytocin signaling pathway in the etiology of autism and, for the first time, implicate the epigenetic regulation of OXTR in the development of the disorder. See the related commentary by Gurrieri and Neri: http://www.biomedcentral.com/1741-7015/7/63

Abstract Leeches are famous for their high medical value and wide environmental adaptability. Among them, cave leeches are a very fascinating and rare group, which is an important component in the study of adaptive evolution of leeches. However, no study has yet reported a reference genome for this group. In this study, we assembled a high-quality chromosome-level genome of the cave terrestrial leech Sinospelaeobdella cavatuses, through Illumina and PacBio sequencing, alongside chromosome conformation capture techniques. The resulting genome spans 153.67 Mb across 9 pseudochromosomes(range: 11.33 to 23.53 Mb), with a mounting rate of up to 95.37% and features an N50 length of 17.15 Mb. This genome is composed of 35.16% repetitive elements and contains 21180 predicted protein-coding genes. Decoding the S. cavatuses genome not only promotes future studies on study of its phylogeny, evolution, and behavior, but also provides valuable resources for in-depth investigation on adaptive evolution of leech.

A novel wire-arc additive manufacturing (WAAM) process utilising titanium flux-cored wire (FCW) containing TiB2, Al60V40 and Ti6Al4V powders was proposed for fabricating TiB/Ti6Al4V composites. The FCW exhibited the capability in customising the composition of TiB/Ti6Al4V composites from hypoeutectic to hypereutectic by tailoring the proportion of TiB2 in blended powders. The comprehensive influence of TiB2 content on molten pool flow, compositional homogeneity and porosity of as-printed composites was attributed to the reduction of melt flowability, driven by viscosity escalation. It was unravelled the porosity was the intrinsic deficiency for the FCW-WAAM process, originating from the gases within FCW, while the interlayered TiB clusters were caused by the lagging melt of TiB2 powders. Due to directional solidification, TiB whiskers possessed a large aspect ratio and were partial to upward growth in hypoeutectic composites, which enhanced the load transfer strengthening. However, the porosity degraded the ductility of composites and caused the variation in mechanical performance.

[Objective] DC circuit breaker is a key equipment in metro traction power supply system. To improve the reliability of the traction and power supply system through reasonable maintenance strategy, it is necessary to evaluate the health condition of DC circuit breaker accurately. [Method] Health indexes are used to characterize the overall health condition of the equipment and establish a comprehensive evaluation model of the equipment health condition. On the basis that the changes of the equipment characteristic parameters reflect the equipment health condition, evaluation indexes are reasonably selected and a multi-index evaluation system of equipment operating condition is established. With the method of hierarchy and entropy weight, the calculation method of the weight of each sub-index is improved, making the equipment health condition evaluation model more reasonable. The equipment health index is calculated based on the evaluation model, and the service life model based on historical health data is established to fit the trend of the equipment health index, evaluate the future health condition and predict the remaining service life. The proposed evaluation model is validated by the actual data of a traction substation. [Result & Conclusion] The example analysis results show that the proposed evaluation model of DC circuit breaker is effective and rational to some extent in that it can scientifically judge and predict the healthy condition and remaining service life of the DC circuit breaker.

This paper presents a novel hybrid algorithm that combines the Butterfly Optimization Algorithm (BOA) and Quantum-behavior Particle Swarm Optimization (QPSO) algorithms, leveraging $ gbest $ to establish an algorithm communication channel for cooperation. Initially, the population is split into two equal subgroups optimized by BOA and QPSO respectively, with the latter incorporating the Lévy flight for enhanced performance. Subsequently, a hybrid mechanism comprising a weight hybrid mechanism, a elite strategy, and a diversification mechanism is introduced to blend the two algorithms. Experimental evaluation on 12 benchmark test functions and the Muskin model demonstrates that the synergy between BOA and QPSO significantly enhances algorithm performance. The hybrid mechanism further boosts algorithm performance, positioning the new algorithm as a high-performance method. In the Muskingum model experiment, the algorithm proposed in this article can give the best sum of the square of deviation (SSQ) and is superior in the comparison of other indicators. Overall, through benchmark test function experiments and Muskin model evaluations, it is evident that the algorithm proposed in this paper exhibits strong optimization capabilities and is effective in addressing practical problems.

Copper-based pesticides are extensively used in agriculture, yet their impacts on beneficial insects remain poorly understood. Here, we investigate how cupric chloride exposure affects the gut microbiome of Bombyx mori, a model organism crucial for silk production. Using 16S rRNA sequencing, we analyzed the gut bacterial communities of fifth-instar silkworm larvae exposed to different concentrations of cupric chloride (0, 4, and 8 g/kg) in an artificial diet. The high-dose exposure dramatically altered the microbial diversity and community structure, where the Bacteroidota abundance decreased from 50.43% to 23.50%, while Firmicutes increased from 0.93% to 18.92%. A network analysis revealed complex interactions between the bacterial genera, with Proteobacteria and Firmicutes emerging as key players in the community response to copper stress. The functional prediction indicated significant shifts in metabolic pathways and genetic information processing in the high-dose group. Notably, the low-dose treatment induced minimal changes in both the taxonomic composition and predicted functions, suggesting a threshold effect in the microbiome response to copper exposure. Our findings provide novel insights into how agricultural chemicals influence insect gut microbiota and highlight potential implications for silkworm health and silk production. This work contributes to understanding the ecological impacts of copper-based pesticides and may inform evidence-based policies for their use in sericulture regions.

The transition from traditional mulberry leaf feeding to artificial diet cultivation represents a major advancement in modern sericulture, yet the genetic mechanisms driving this adaptation remain largely unexplored. This study investigates the genomic basis of artificial diet adaptation in the silkworm strain Guican No.5 through whole-genome resequencing and transcriptome analysis. We identified 8,935,179 single-nucleotide polymorphisms (SNPs) across all chromosomes, accounting for 2.01% of the genome, with particularly high densities observed in chromosomes 23, 26, and 28. Our analysis also revealed 879 novel transcripts, many of which are involved in digestion, detoxification, and stress response pathways. Key novel genes, including three carboxylesterases, two cytochrome P450s, one heat shock protein, and one copper/zinc superoxide dismutase, exhibited varying degrees of sequence similarity to known proteins, suggesting modifications to existing genetic frameworks. Notably, one novel P450 gene displayed only 74.07% sequence identity with its closest homolog, indicating the emergence of a new protein sequence. Additionally, several key genes showed high similarity to wild silkworm (Bombyx mandarina) proteins, underscoring their evolutionary origins. These findings provide valuable insights into the molecular mechanisms underpinning artificial diet adaptation in silkworms and offer genomic resources to enhance artificial diet formulations and breeding programs in sericulture.

Ferns represent the second-largest group of vascular plants, yet their genomic resources lag far behind. Here, we present a chromosome-scale genome assembly of Cibotium barometz (L.) J. Sm., a medicinally important fern species. The 3.49 Gb genome, assembled into 66 chromosomes with 99.41% sequence anchorage, revealed an exceptionally high proportion (83.93%) of repetitive elements, dominated by recently expanded LTR retrotransposons. We identified 30,616 protein-coding genes, providing insights into fern-specific gene families. Genomic analyses uncover the evolutionary dynamics of 513 key biosynthetic genes, particularly those involved in terpenoid and flavonoid production. Expression profiling across tissues revealed tissue-specific regulation of these pathways, with notable upregulation of chalcone synthase genes in roots. Our structural analysis of 1-deoxy-d-xylulose-5-phosphate synthase, a key enzyme in terpenoid biosynthesis, demonstrated high conservation across land plants while highlighting fern-specific adaptations. The identification of multiple isoforms for key enzymes points to potential gene-duplication events or the evolution of fern-specific variants. This genome provides a foundation for understanding fern biology, evolution, and the molecular basis of their medicinal properties. It also offers valuable resources for conservation efforts and pharmacological research, paving the way for sustainable utilization of this valuable medicinal plant and advancing our understanding of plant diversity and natural product biosynthesis.

To assess the possible role of familial psychopathology in the etiology of infantile autism, family histories and neurological status of 51 autistic subjects subgrouped by level of language function were evaluated. Among findings was a high incidence of Asperger's Syndrome in family members of high functioning autistic subjects. (Author/DB)

The gut microbiome significantly influences the health and productivity of silkworms (Bombyx mori), the cornerstone of sericulture. With the increasing use of cost-effective artificial diets in sericulture, it is crucial to understand how these diets impact the silkworm gut microbiomes. Here we employed 16S rRNA sequencing to delineate the impact of three distinct dietary regimens on the silkworm gut microbiomes: exclusive mulberry leaf diet (SY), exclusive artificial feed diet (SL), and a sequential transition from artificial feed to mulberry leaves (ZS). Our results unveiled stark differences in microbial diversity across the groups, with the ZS group displaying an intermediary complexity. LefSe and random forest analyses identified Methylobacteriaceae, Microbacterium, and Rhodococcus as significantly enriched in the ZS group, suggesting their potential to facilitate silkworms’ adaptation to dietary transitions. Functional profiling revealed differential pathway regulation, indicating a metabolic reconfiguration in response to dietary modulations. Notably, the enrichment of Lactobacillus and Weissella in both the SL and ZS groups highlights their potential as probiotics in artificial diets. Our findings provide insights into the diet adaptation mechanisms of silkworm gut microbiota, paving the way for harnessing the intestinal bacteria to enhance silkworm health and silk production through targeted microbial interventions in sericulture practices.

As one of the key enzymes that maintain the dynamic balance of metal content in animals and take part in the process of heavy metals detoxification, metallothionein (MT) is also associated with the process of immune response. In this study, the full-length metallothionein cDNA sequence of 324 bp from Mytilus coruscus was obtained (named as McMT) with a 222bp ORF encoding 73 amino acid residues in length and its theoretical pI/MW was 7.75/7.21 kDa. Blastp showed that the deduced amino acid sequence of McMT had significant homology with metallothionein from many animals, plants and bacteria, especially with other known MT of mollusca, for example Mytilus edulis and Mytilus galloprovincialis and they fell into the same evolutionary branch. Real-time PCR was used to examine the transcript pattern of McMT in hemocyte, gill, hepatopancreas, gonad, adductor and mantle. The highest transcript level appeared in hepatopancreas, which showed its multiple physiological roles with relation to the tissue type and the maximum expression in hepatopancreas could contribute to detoxification. Under the stress of heavy metal exposure for 15 days, the time-dependent expression pattern of McMT was observed in each treated group, but the highest expression appeared at different times for various concentrations of Cu2+ and Pb2+. The temporal expression of McMT after bacteria (Vibrio parahemolyticus and Aeromonas hydrophila) challenge firstly rose and then went down, and the expression peak appeared at 4h after V.parahemolyticus infection with 40-fold and 100-fold under A.hydrophila stress at 24h. The results suggested that McMT played a significant role in antioxidation and the expression of McMT can be used as a biomarker for monitoring the situation of marine pollution.

Satyrinae is a 3000-species butterfly subfamily of Nymphalidae. The higher-level classification of this family is still controversial. In this research, we sequenced the complete mitogenomes of three satyrid butterfly species, Hipparchia autonoe, Paroeneis palaearctica, and Oeneis buddha, and studied the phylogeny of Satyrinae with all known complete mitogenomes. The results showed that the lengths of the three satyrid butterfly mitogenomes are 15,435 bp (H. Autonoe), 15,942 bp (P. palaearctica), and 15,259 bp (O. buddha). Gene content and arrangement of newly sequenced mitogenomes are highly conserved and are typical of Lepidoptera. These three mitogenomes were found to have a typical set of 37 genes and an A + T-rich region. The tRNA genes in these three mitogenomes showed a typical clover leaf structure, but the stem of tRNASer (AGN) was lacking dihydroacridine. In these three species, the lengths of the A + T-rich regions were different, which led to differences in mitochondrial genome sizes. The characterizations of the three mitogenomes enrich our knowledge on the Lepidopteran mitogenome and provide us genetic information to reconstruct the phylogenetic tree. Finally, the phylogenetic results confirmed the position of the genus Davidina in the subfamily Satyrini, had a closer phylogenetic relationship with Oeneis, and the phylogenetic analysis supported the formation of Oeneis buddha as an independent taxon in Oeneis.

Several candidate gene studies support RELN as susceptibility gene for autism. Given the complex inheritance pattern of autism, it is expected that gene-gene interactions will exist. A logical starting point for examining potential gene-gene interactions is to evaluate the joint effects of genes involved in a common biological pathway. RELN shares a common biological pathway with APOE, and Persico et al. have observed transmission distortion of the APOE-2 allele in autism families.We evaluated RELN and APOE for joint effects in autism susceptibility.A total of 470 Caucasian autism families were analyzed (265 multiplex; 168 trios with no family history; 37 positive family history but only one sampled affected). These families were genotyped for 11 RELN polymorphisms, including the 5′ untranslated region repeat previously associated with autism, as well as for the APOE functional allele. We evaluated single locus allelic and genotypic association with the pedigree disequilibrium test and geno-PDT, respectively. Multilocus effects were evaluated using the extended version of the multifactorial dimensionality reduction method.For the single locus analyses, there was no evidence for an effect of APOE in our data set. Evidence for association with RELN (rs2073559; trio subset P=0.07 PDT; P=0.001 geno-PDT; overall geno-PDT P=0.05), however, was found. For multilocus geno-PDT analysis, the joint genotype of APOE and RELN rs2073559 was highly significant (trio subset, global P=0.0001), probably driven by the RELN single locus effect. Using the extended version of the multifactorial dimensionality reduction method to detect multilocus effects, there were no statistically significant associations for any of the n-locus combinations involving RELN or APOE in the overall or multiplex subset. In the trio subset, 1-locus and 2-locus models selected only markers in RELN as best models for predicting autism case status.Thus, we conclude that there is no main effect of APOE in our autism data set, nor is there any evidence for a joint effect of APOE with RELN. RELN, however, remains a good candidate for autism susceptibility. [ABSTRACT FROM AUTHOR]

Gene-gene interactions are likely involved in many complex genetic disorders and new statistical approaches for detecting such interactions are needed. We propose a multi-analytic paradigm, relying on convergence of evidence across multiple analysis tools. Our paradigm tests for main and interactive effects, through allele, genotype and haplotype association. We applied our paradigm to genotype data from three GABAA receptor subunit genes ( GABRB3, GABRA5, and GABRG3) on chromosome 15 in 470 Caucasian autism families. Previously implicated in autism, we hypothesized these genes interact to contribute to risk. We detected no evidence of main effects by allelic (PDT, FBAT) or genotypic (genotype-PDT) association at individual markers. However, three two-marker haplotypes in GABRG3 were significant (HBAT). We detected no significant multi-locus associations using genotype-PDT analysis or the EMDR data reduction program. However, consistent with the haplotype findings, the best single locus EMDR model selected a GABRG3 marker. Further, the best pairwise genotype-PDT result involved GABRB3 and GABRG3, and all multi-locus EMDR models also selected GABRB3 and GABRG3 markers. GABA receptor subunit genes do not significantly interact to contribute to autism risk in our overall data set. However, the consistency of results across analyses suggests that we have defined a useful framework for evaluating gene-gene interactions. [ABSTRACT FROM AUTHOR]

States that Hotien prefecture, Xinjiang Province, China, in the Taklamakan Desert, is an area of severe iodine deficiency. When iodine supplementation began in the area; How the supplementation was conducted; Success of the method used.

Induction of cytochrome P-4501A protein and induction of related enzyme activity are hallmark physiological responses following exposure to planar halogenated aromatic hydrocarbons (HAHs) such as 3,3',4,4',5-pentachlorobiphenyl (PCB 126; PeCB). Environments contaminated by HAHs are often contaminated by mixtures of anthropogenic contaminants, including organometallic compounds. Both HAHs and organometallics easily bioconcentrate and bioaccumulate in aquatic food chains that may ultimately be linked to humans through seafood consumption. Tributyltin (TBT), a marine biocide, has been detected in many aquatic environments due to its primary use as a marine antifoulant agent. Exposure to TBT, as well as several PCBs, has been associated with immunotoxicity, neurotoxicity, and endocrine disruption. Recently TBT has been shown to inhibit cytochrome P-4501A activity in vitro, but information concerning these effects in vivo and in combination with classical inducers of P-4501A, such PeCB, is lacking. We exposed female B6C3F1 mice to 0.01, 0.1, and 1.0 mg/kg PeCB, TBT, or both in combination, with corn oil (CO) serving as a carrier control. Cytochrome P-4501A protein levels and related benzo\[a]pyrene hydroxylation (BaP-OHase) activity were measured following a single acute intraperitoneal (ip) dose or seven daily injections. Body, thymus, and liver weights were used to monitor general physiological responses following exposure. P4501A levels and BaP-OHase activity were significantly elevated in mice exposed to PeCB alone. This effect was enhanced by coexposure to low levels of TBT; PeCB-induced P4501A-related activity was potentiated at the low range of each. The highest dose of TBT, however, inhibited these activities when given in combination with PeCB. Thymic atrophy was evident only in mice exposed daily to 0.1 and 1.0 mg/kg PeCB alone, or to a combination of the lowest and highest dose of PeCB and TBT, respectively. Because environmental levels of TBT are not expected to be as high as the highest level used in our toxicological studies, we conclude that environmental exposure to TBT may potentiate, rather than inhibit, the activity of environmental levels of HAHs that are associated with P4501A induction. [ABSTRACT FROM AUTHOR]

Abstract. The pathogenesis of Reye's syndrome encephalopathy was analyzed in terms of uniform criteria designed to clarify and assist evaluation of the leading hypotheSes. Three of these hypotheses derive from known metabolic sequelae of hepatic mitochondrial dysfunction and the severe systemic catabolism of protein, fats, and carbohydrates that characterize the syndrome biochemically: hyperammonemia, hyperfattyacidemia, and hyperlactatemia. In addition, there is a fourth hypothesis of generalized mitochondrial insult affecting brain, muscle, and other organs as well as liver. The weight of evidence favors hyperammonemia as a sufficient factor while recognizing important interrelationships with the other observed biochemical derangements. How the catabolism and hepatic mitochondrial dysfunction are produced by the triggering viral infection remains unknown. Therapeutic efforts have thus far not succeeded in definitive metabolic intervention. Such reversal of the clinical Syndrome would lead to confirmation of the necessary pathogenetic factors; this type of intervention remains the chief goal of metabolic research in Reye's syndrome. [ABSTRACT FROM AUTHOR]

Brain development in humans is remarkably resistant to permanent damage from protein-energy malnutrition. However, specific nutrients have crucial roles. Iodine deficiency is the most important and widespread nutrient deficiency; it causes endemic cretinism. associated with deaf-mutism and cerebral palsy. Iodine deficiency during pregnancy causes both maternal and fetal hypothyroxinemia, resulting in irreversible impairment of brain development at a critical stage. Neuropathological data place this after 14 wk, perhaps continuing through the third trimester. Gross brain structure, including the gyral pattern of the cerebral cortex. develops normally; the insult affects neuron and dendrite growth. Recent magnetic-resonance-imaging (MRI) images of neurological cretin brains show remarkably normal appearance except for gliotic lesions of the globus pallidus. correlating with the proximal motor rigidity seen clinically. Myxedematous cretinism is paradoxical in showing more severe hypothyroidism and growth failure, yet better intellectual, motor, and hearing function: these observations implicate a second independent factor in its pathogenesis. [ABSTRACT FROM AUTHOR]