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A Negishi coupling based synthesis of 1,2,4,5-tetra(9-anthryl)benzene derivatives, possessing X-shaped molecular structures, is described. The results of X-ray crystallographic analysis show that two-dimensional highly ordered packing structure of the crystalline state of the unsubstituted derivative is a consequence of intermolecular π-π and CH-π interactions between anthracene units. Photoirradiation of the unsubstituted derivative as a precipitated solution promotes intramolecular [4+4] photocycloaddition reactions between both adjacent pairs of anthracene units to produce a crystalline polycyclic product having a unique 1.700 Å long carbon-carbon single bond. Furthermore, charge-transfer complexes, displaying near-infrared absorption and emission, are generated by co-crystallization of the X-shaped unsubstituted member of the group with electron-acceptor molecules.

Purpose:KRAS is among the most commonly mutated oncogene in cancer including non–small cell lung cancer (NSCLC). In early clinical trials, inhibitors targeting G12C-mutant KRAS have achieved responses in some patients with NSCLC. Possible intrinsic and acquired resistance mechanisms to KRAS G12C inhibitors are not fully elucidated and will likely become important to identify.Experimental Design:To identify potential resistance mechanisms, we defined the sensitivity of a panel of KRAS G12C–mutant lung cancer cell lines to a KRAS G12C inhibitor, AMG510. Gene set enrichment analyses were performed to identify pathways related to the sensitivity, which was further confirmed biochemically. In addition, we created two cell lines that acquired resistance to AMG510 and the underlying resistance mechanisms were analyzed.Results:KRAS expression and activation were associated with sensitivity to KRAS G12C inhibitor. Induction of epithelial-to-mesenchymal transition (EMT) led to both intrinsic and acquired resistance to KRAS G12C inhibition. In these EMT-induced cells, PI3K remained activated in the presence of KRAS G12C inhibitor and was dominantly regulated by the IGFR–IRS1 pathway. We found SHP2 plays a minimal role in the activation of the PI3K pathway in contrast to its critical role in the activation of the MAPK pathway. The combination of KRAS G12C inhibitor, PI3K inhibitor, and SHP2 inhibitor resulted in tumor regressions in mouse models of acquired resistance to AMG510.Conclusions:Our findings suggest that EMT is a cause of both intrinsic and acquired resistance by activating the PI3K pathway in the presence of KRAS G12C inhibitor.

Supplementary Methods, Supplementary Table S1 to S4, and Supplementary Figure S1 to S4.

Williams syndrome (WS) is a rare genetic disorder caused by a microdeletion at the 7q11.23 region and is characterized by diverse symptoms encompassing physical and cognitive features. WS was reported to be associated to altered DNA methylation (DNAm) patterns. However, due to the limited information from long-term studies, it remains unclear whether WS accelerates aging. Genome-wide DNAm profiles can serve as "epigenetic clocks" to help estimate biological aging along with age-related markers, such as plasma proteins and telomere length.We investigated GrimAge, DNAm-based telomere length (DNAmTL), and other epigenetic clocks in blood samples of 32 patients with WS and 32 healthy controls.We observed a significant acceleration in GrimAge, DNAmTL, and other epigenetic clocks in patients with WS as compared with those of controls. In addition, several GrimAge components, such as adrenomedullin, growth differentiation factor-15, leptin and plasminogen activator inhibitor-1, were altered in patients with WS.This study provides novel evidence supporting the hypothesis that WS may be associated to accelerated biological aging. A better understanding of the overall underlying biological effects of WS can provide new foundations for improved patient care; thus, long-term follow-up studies are still warranted.

This study examined the similarities/differences between the social phenotypes of Williams syndrome (WS) and autism spectrum disorder (ASD). As cultural norms may affect symptom evaluation, this study administered the Social Responsiveness Scale-2 to Japanese individuals with WS (n = 78, 4.4-44.0 years) and ASD (n = 75, 4.7-55.4 years). The scores for Social Motivation and Social Communication were significantly more severe in the ASD than WS group. Overall, the similarities and differences between the social phenotypes of the syndromes were consistent with the findings of a recent study conducted in the UK, except for the social awareness subscale score. This highlights the importance of cross-cultural investigations of WS and ASD.

Overcrowded ethylenes composed of 10-methyleneanthrone and two bulky aromatic rings contain a twisted carbon-carbon double (C=C) bond as well as a folded anthrone unit. As such, they are unique frustrated aromatic enes (FAEs). Various colored crystals of these FAEs, obtained using different solvents, correspond to multiple metastable conformations of the FAEs with various twist and fold angles of the C=C bond, as well as various dihedral angles of attached aryl units with respect to the C=C bond. The relationships between color and these parameters associated with conformational features around the C=C bond were elucidated using experimental and theoretical studies. Owing to the fact that they are separated by small energy barriers, the variously colored conformations in the FAE crystal change in response to various external stimuli, such as mechanical grinding, hydrostatic pressure and thermal heating.

Purpose: KRAS is among the most commonly mutated oncogene in cancer including non–small cell lung cancer (NSCLC). In early clinical trials, inhibitors targeting G12C-mutant KRAS have achieved responses in some patients with NSCLC. Possible intrinsic and acquired resistance mechanisms to KRAS G12C inhibitors are not fully elucidated and will likely become important to identify. Experimental Design: To identify potential resistance mechanisms, we defined the sensitivity of a panel of KRAS G12C–mutant lung cancer cell lines to a KRAS G12C inhibitor, AMG510. Gene set enrichment analyses were performed to identify pathways related to the sensitivity, which was further confirmed biochemically. In addition, we created two cell lines that acquired resistance to AMG510 and the underlying resistance mechanisms were analyzed. Results: KRAS expression and activation were associated with sensitivity to KRAS G12C inhibitor. Induction of epithelial-to-mesenchymal transition (EMT) led to both intrinsic and acquired resistance to KRAS G12C inhibition. In these EMT-induced cells, PI3K remained activated in the presence of KRAS G12C inhibitor and was dominantly regulated by the IGFR–IRS1 pathway. We found SHP2 plays a minimal role in the activation of the PI3K pathway in contrast to its critical role in the activation of the MAPK pathway. The combination of KRAS G12C inhibitor, PI3K inhibitor, and SHP2 inhibitor resulted in tumor regressions in mouse models of acquired resistance to AMG510. Conclusions: Our findings suggest that EMT is a cause of both intrinsic and acquired resistance by activating the PI3K pathway in the presence of KRAS G12C inhibitor.

Flexible and aromatic photofunctional system (FLAP) has been recognized as an emerging class of versatile π-conjugated molecules. Here we report a viscosity-probing function of flapping peryleneimi...

Understanding the microviscosity of soft condensed matter is important to clarify the mechanisms of chemical, physical or biological events occurring at the nanoscale. Here, we report that flapping fluorophores (FLAP) can serve as microviscosity probes capable of detecting small changes. By the ratiometric fluorescence analysis, one of the FLAP probes detects a macroscopic viscosity change of a few cP, occurring at the thermal phase transition of a nematic liquid crystal. We discuss the impact of the chemical structure on the detection capability, and the orientation of the FLAP molecules in the ground and excited states. This work contributes to experimentally providing a molecular picture of liquid crystals, which are often viewed as a continuum.

We aimed to determine the similarities and differences in the roles of genic and regulatory copy number variations (CNVs) in bipolar disorder (BD), schizophrenia (SCZ), and autism spectrum disorder (ASD).Based on high-resolution CNV data from 8708 Japanese samples, we performed to our knowledge the largest cross-disorder analysis of genic and regulatory CNVs in BD, SCZ, and ASD.In genic CNVs, we found an increased burden of smaller (100 kb) exonic deletions in BD, which contrasted with the highest burden of larger (500 kb) exonic CNVs in SCZ/ASD. Pathogenic CNVs linked to neurodevelopmental disorders were significantly associated with the risk for each disorder, but BD and SCZ/ASD differed in terms of the effect size (smaller in BD) and subtype distribution of CNVs linked to neurodevelopmental disorders. We identified 3 synaptic genes (DLG2, PCDH15, and ASTN2) as risk factors for BD. Whereas gene set analysis showed that BD-associated pathways were restricted to chromatin biology, SCZ and ASD involved more extensive and similar pathways. Nevertheless, a correlation analysis of gene set results indicated weak but significant pathway similarities between BD and SCZ or ASD (r = 0.25-0.31). In SCZ and ASD, but not BD, CNVs were significantly enriched in enhancers and promoters in brain tissue.BD and SCZ/ASD differ in terms of CNV burden, characteristics of CNVs linked to neurodevelopmental disorders, and regulatory CNVs. On the other hand, they have shared molecular mechanisms, including chromatin biology. The BD risk genes identified here could provide insight into the pathogenesis of BD.

In this paper, a method to design the power flow and energy management controller is proposed, for a hybrid energy storage system with battery and EDLC on an assumed electric vehicle. Numerical simulation under an assumed speed profile is carried out to reveal the power and the energy profile of the ESDs under the wide frequency range of the load power. The overall loss in the ESDs and the DC/DC converter are evaluated, according to the power and the energy profile of the ESDs. The time constant of the filter $T_{EDLC}$ for the controller is proposed to be set shorter as far to smooth the battery power not to absorb the regenerative power. EDLC is mounted less as far not to increase to the energy loss in the EDLC, under the condition of the designed controller.

A differential laser Doppler velocimeter using 48-channel spatial encoded measurement points is proposed for dense cross-sectional velocity distribution measurements. An asymmetrical push–pull configuration and multiple photodiodes are employed to increase the number of the measurement points. The functionality of the proposed structure is experimentally demonstrated. The results indicate that a cross-sectional velocity distribution is successfully measured with the proposed structure.

Spinach (Spinacia oleracea L.) is a highly nutritious leafy vegetable and an economically important food crop. The wild species S. turkestanica Iljin and S. tetrandra Steven ex M. Bieb. are inter-fertile with cultivated spinach and constitute important sources of novel characters to improve spinach varieties, such as for their resistance to pests and diseases. Despite their relevance in plant breeding, S. turkestanica and S. tetrandra are poorly represented in genetic resources collections. Among the reasons for these collection gaps are the difficulties in propagating these species ex situ. Here we report on the results of collecting expeditions for S. turkestanica in Central Asia and for S. tetrandra in the Trans-Caucasus, which were organized by the Dutch gene bank in collaboration with several breeding companies. Furthermore, we also present efficient protocols for the ex situ regeneration of these species. These protocols were used to successfully regenerate 66 S. turkestanica and 36 S. tetrandra samples from the collecting expeditions. These new accessions fill up important collection gaps in ex situ conserved genetic resources of spinach and can be used for exploitation in crop improvement.

We propose an exact optimization method for home healthcare delivery that relies on logic-based Benders decomposition (LBBD). The objective is to match patients with healthcare aides and schedule multiple home visits over a given time horizon, to maximize the number of patients served while taking into account patient requirements, travel time, and scheduling constraints. Unlike classical Benders methods, LBBD allows us to exploit a natural decomposition of the problem into a master problem, solved by mixed integer programming, and a subproblem that decouples into small scheduling problems, solved by constraint programming. We report computational results based on data obtained from a major home hospice care provider. We find that LBBD is far superior to mixed integer programming on all but a few instances with narrow time windows. It solves problems of realistic size to optimality if the aim is to conduct staff planning on a rolling basis, without temporal dependencies between visits. We also find that a version of LBBD known as branch and check usually outperforms standard LBBD on the instances tested.

Conjugated linolenic acids (CLNs) are naturally occurring fatty acids that are believed to have anticancer properties. In this study, we examined various plant seeds from herbs to discover seed oils containing CLNs. The ultraviolet spectra of total lipids from these seeds were measured. An absorption maximum around 270 nm was observed in seed oils belonging to the Valerianaceae family (Centranthus ruber and Valeriana officinalis). When the fatty acid compositions of these seed oils were measured, CLNs were detected. By silica column chromatography, neutral lipids (NLs), glycolipids, and phospholipids were eluted from seed oils of C. ruber and V. officinalis. Then, fatty acid compositions of these fractions were measured. This revealed that most of the CLNs in these seed oils existed in the NL fraction. When the NL fractions of these seed oils were reacted with lipase, CLNs showed good sensitivity to lipase hydrolysis. This suggested that the CLNs in the seed oils of C. ruber and V. officinalis existed predominantly at the sn-1,3 position of triacylglycerol and less at the sn-2 position. These results suggested that the CLNs from the seed oils of C. ruber and V. officinalis could easily be taken up by cancer cells as free fatty acids and had good potential as antitumor substances.

Dysregulation of epigenetic processes involving histone methylation induces neurodevelopmental impairments and has been implicated in schizophrenia (SCZ) and autism spectrum disorder (ASD). Variants in the gene encoding lysine demethylase 4C (KDM4C) have been suggested to confer a risk for such disorders. However, rare genetic variants in KDM4C have not been fully evaluated, and the functional impact of the variants has not been studied using patient-derived cells. In this study, we conducted copy number variant (CNV) analysis in a Japanese sample set (2605 SCZ and 1141 ASD cases, and 2310 controls). We found evidence for significant associations between CNVs in KDM4C and SCZ (p = 0.003) and ASD (p = 0.04). We also observed a significant association between deletions in KDM4C and SCZ (corrected p = 0.04). Next, to explore the contribution of single nucleotide variants in KDM4C, we sequenced the coding exons in a second sample set (370 SCZ and 192 ASD cases) and detected 18 rare missense variants, including p.D160N within the JmjC domain of KDM4C. We, then, performed association analysis for p.D160N in a third sample set (1751 SCZ and 377 ASD cases, and 2276 controls), but did not find a statistical association with these disorders. Immunoblotting analysis using lymphoblastoid cell lines from a case with KDM4C deletion revealed reduced KDM4C protein expression and altered histone methylation patterns. In conclusion, this study strengthens the evidence for associations between KDM4C CNVs and these two disorders and for their potential functional effect on histone methylation patterns.

Attention deficit-hyperactivity disorder (ADHD) is a prevalent neuropsychiatric disorder found in children. It is characterized by inattention, hyperactivity, and impulsivity. Methylphenidate (MPH) and atomoxetine (ATX) are commonly prescribed for the treatment of ADHD. In the present study, we examined the behavioral and brain transcriptome changes in MPH-treated and ATX-treated zebrafish. In behavioral analysis, zebrafish showed opposite response to each treatment. MPH-treated fish showed higher anxiety-like behavior while ATX-treated fish showed lower anxiety-like behavior. Further, we performed RNA sequencing analysis of zebrafish brain to elucidate the underlying biological pathways associated with MPH and ATX treatment. Interestingly, we found that shared differentially expressed genes in MPH-treated and ATX-treated fish were instrumental in cholesterol biosynthesis pathway and were regulated in opposite manner. Our findings highlight the contrast between MTH and ATX, and may suggest the alterations in clinical practice for these medications and drug development for ADHD., 2種類のADHD治療薬が対照的な作用を持つことを発見 --ゼブラフィッシュで行動や脳での働きを探る--. 京都大学プレスリリース. 2020-05-18.

Flapping fluorophores (FLAP) with a flexible 8π ring are rapidly gaining attention as a versatile photofunctional system. Here we report a highly photostable "flapping peryleneimide" with an unprecedented fluorogenic mechanism based on a bent-to-planar conformational change in the S1 excited state. The S1 planarization induces an electronic configurational switch, almost quenching the inherent fluorescence (FL) of the peryleneimide moieties. However, the FL quantum yield is remarkably improved with a prolonged lifetime upon a slight environmental change. This fluorogenic function is realized by sensitive π-conjugation design, as a more π-expanded analogue does not show the planarization dynamics. With strong visible-light absorption, the FL lifetime response synchronized with the flexible flapping motion is useful for the latest optical techniques such as FL lifetime imaging microscopy (FLIM).

Background Williams syndrome (WS) is a neurodevelopmental disorder that has been attributed to heterozygous deletions in chromosome 7q11.23 and exhibits a variety of physical, cognitive, and behavioral features. However, the genetic basis of this phenotypic variability is unclear. In this study, we identified genetic clues underlying these complex phenotypes. Methods Neurobehavioral function was assessed in WS patients and healthy controls. Total RNA was extracted from peripheral blood and subjected to microarray analysis, RNA‐sequencing, and qRT‐PCR. Weighted gene co‐expression network analysis was performed to identify specific alterations related to intermediate disease phenotypes. To functionally interpret each WS‐related module, gene ontology and disease‐related gene enrichment were examined. We also investigated the micro (mi)RNA expression profiles and miRNA co‐expression networks to better explain the regulation of the transcriptome in WS. Results Our analysis identified four significant co‐expression modules related to intermediate WS phenotypes. Notably, the three upregulated WS‐related modules were composed exclusively of genes located outside the 7q11.23 region. They were significantly enriched in genes related to B‐cell activation, RNA processing, and RNA transport. BCL11A, which is known for its association with speech disorders and intellectual disabilities, was identified as one of the hub genes in the top WS‐related module. Finally, these key upregulated mRNA co‐expression modules appear to be inversely correlated with a specific downregulated WS‐related miRNA co‐expression module. Conclusions Dysregulation of the mRNA/miRNA network involving genes outside of the 7q11.23 region is likely related to the complex phenotypes observed in WS patients., Read the Commentary on this article at doi: 10.1111/jcpp.13056

Summary: Compelling evidence in Caucasian populations suggests a role for copy-number variations (CNVs) in autism spectrum disorder (ASD) and schizophrenia (SCZ). We analyzed 1,108 ASD cases, 2,458 SCZ cases, and 2,095 controls in a Japanese population and confirmed an increased burden of rare exonic CNVs in both disorders. Clinically significant (or pathogenic) CNVs, including those at 29 loci common to both disorders, were found in about 8% of ASD and SCZ cases, which was significantly higher than in controls. Phenotypic analysis revealed an association between clinically significant CNVs and intellectual disability. Gene set analysis showed significant overlap of biological pathways in both disorders including oxidative stress response, lipid metabolism/modification, and genomic integrity. Finally, based on bioinformatics analysis, we identified multiple disease-relevant genes in eight well-known ASD/SCZ-associated CNV loci (e.g., 22q11.2, 3q29). Our findings suggest an etiological overlap of ASD and SCZ and provide biological insights into these disorders. : Kushima et al. perform comparative analyses of CNVs in ASD and SCZ in a Japanese population. They identify pathogenic CNVs and biological pathways in each disorder with significant overlap. Patients with pathogenic CNVs have a higher prevalence of intellectual disability. Disease-relevant genes are detected in eight well-known ASD/SCZ-associated CNV loci. Keywords: autism spectrum disorder, schizophrenia, copy-number variation, array comparative genomic hybridization, genetic overlap, Japanese population, oxidative stress response, genome integrity, lipid metabolism, gene ontology

This study assessed the effects of constant and diurnally fluctuating pCO2 on development and shell formation of larval abalone Haliotis discus hannai. The larvae was exposed to different pCO2 conditions; constant [450, 800, or 1200 μatm in the first experiment (Exp. I), 450 or 780 μatm in the second experiment (Exp. II)] or diurnally fluctuating pCO2 (800 ± 400 or 1200 ± 400 μatm in Exp. I, 450 ± 80, 780 ± 200 or 780 ± 400 μatm in Exp. II). Mortality, malformation rates or shell length of larval abalone were not significantly different among the 450, 800, and 800 ± 400 μatm pCO2 treatments. Meanwhile, significantly higher malformation rates and smaller shells were detected in the 1200 and 1200 ± 400 μatm pCO2 treatments than in the 450 μatm pCO2 treatment. The negative impacts were greater in the 1200 ± 400 μatm than in the 1200 μatm. Shell length and malformation rate of larval abalone were related with aragonite saturation state (Ω-aragonite) in experimental seawater, and greatly changed around 1.1 of Ω-aragonite which corresponded to 1000–1300 μatm pCO2. These results indicate that there is a pCO2 threshold associated with Ω-aragonite in the seawater, and that pCO2 fluctuations produce additional negative impacts on abalone when above the threshold. Clear relationships were detected between abalone fitness and the integrated pCO2 value over the threshold, indicating that the effects of OA on development and shell formation of larval abalone can be determined by intensity and time of exposure to pCO2 over the threshold.

In Japan, a unique islanding detection method, named New Islanding Detection Method, is widely equipped with grid-tied photovoltaic generation systems (PVs) to accurately detect their islanding operation. However, some research results show that the extensive installation of new islanding detection method brings negative impacts on stability of main power grids. This is because the islanding detection method has a possibility to detect frequency fluctuation caused by main grid’s faults, and the resulting undesirable operation intensifies the frequency fluctuations more. The authors especially focus on a frequency feedback mechanism in the islanding detection method, and then clarify some impacts on the stability of main grids which are originated from the growth in penetration of the islanding detection method in PVs. Through numerical simulations and discussions on their results, the authors concluded as, (1) the transient stability can be improved when active power output of PVs are set to constant current characteristics, and (2) the dynamic stability can be improved by maintaining constant impedance characteristics in the active power output of PVs when the PVs keep fluctuating the frequency and the voltage in the main power grids.

Increasing evidence suggests that epigenetic mechanisms play a role in the etiology of autism spectrum disorder (ASD). To date, several studies have attempted to identify epigenetic biomarkers for ASD. However, reliable markers remain to be established and most of these studies have focused on pediatric patients with ASD. In this study, we sought to find an epigenetic DNA methylation biomarker from peripheral blood for adult patients with high-functioning ASD. DNA methylation profiles were analyzed using the Illumina 450 K methylation array. To identify robust candidate markers, we employed two types of machine-learning algorithms for marker selection. We identified a potential marker (cg20793532) for which is the AUC value was 0.79. Notably, cg20793532 was annotated to the PPP2R2C gene, which was hypermethylated and down-regulated in blood from ASD patients compared to that in the controls. Although requiring careful interpretation, this pilot study seems to provide a potential blood biomarker for identifying individuals with high-functioning ASD.

Williams syndrome (WS) is caused by a microdeletion of chromosome 7q11.23, and is characterized by various physical and cognitive symptoms. In particular, WS is characterized by hypersocial (overfriendly) behavior; WS has gained attention as aspects of the WS phenotype contrast with those of autism spectrum disorder (ASD). The oxytocin receptor gene (OXTR) contributes to social phenotypes in relation to regulation of oxytocin (OXT) secretion. Additionally, mounting evidence has recently shown that DNA methylation of OXTR is associated with human social behavior. However, the role of OXTR in WS remains unclear. This study investigated the regulation of OXTR in WS. We examined the gene expression levels in blood from WS patients and controls, and then analyzed the methylation levels in two independent cohorts. We showed that OXTR was down-regulated and hypermethylated in WS patients compared to controls. Our findings may provide an insight into OXTR in mediating complex social phenotypes in WS.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social communication deficits and repetitive behaviors. Owing to the difficulty of clinical diagnosis, ASD without intellectual disability (i.e., high-functioning ASD) is often overlooked. MicroRNAs (miRNAs) have been recently recognized as potential biomarkers of ASD as they are dysregulated in various tissues of individuals with ASD. However, it remains unclear whether miRNA expression is altered in individuals with high-functioning ASD. Here, we investigated the miRNA expression profile in peripheral blood from adults with high-functioning ASD, and age and gender-matched healthy controls. We identified miR-6126 as being robustly down-regulated in ASD and correlated with the severity of social deficits. Enrichment analysis of predicted target genes revealed potential association with neurons, synapses, and oxytocin signaling pathways. Our findings may provide insights regarding the molecular clues for recognizing high-functioning ASD.

The first demonstration of a Fermi-level managed barrier (FMB) diode used for a receiver of the wireless communication is presented in the 300-GHz-band. The FMB diode receiver exhibited superior sensitivity over a conventional Schottky-barrier-diode receiver in on-off-keying modulation and direct detection system. Coherent detection scheme with the FMB diode was also demonstrated by applying a local oscillator signal as small as 10 µW to the diode, and an error-free transmission was achieved at data rates up to 12.5 Gbit/s, which is limited by the bandwidth of the transimpedance amplifier integrated with the FMB diode.

Conjugated linolenic acids (CLNs) are naturally occurring fatty acids that are believed to have anticancer properties. In this study, we examined various plant seeds from herbs to discover seed oils containing CLNs. The ultraviolet spectra of total lipids from these seeds were measured. An absorption maximum around 270 nm was observed in seed oils belonging to the Valerianaceae family (Centranthus ruber and Valeriana officinalis). When the fatty acid compositions of these seed oils were measured, CLNs were detected. By silica column chromatography, neutral lipids (NLs), glycolipids, and phospholipids were eluted from seed oils of C. ruber and V. officinalis. Then, fatty acid compositions of these fractions were measured. This revealed that most of the CLNs in these seed oils existed in the NL fraction. When the NL fractions of these seed oils were reacted with lipase, CLNs showed good sensitivity to lipase hydrolysis. This suggested that the CLNs in the seed oils of C. ruber and V. officinalis existed predominantly at the sn-1,3 position of triacylglycerol and less at the sn-2 position. These results suggested that the CLNs from the seed oils of C. ruber and V. officinalis could easily be taken up by cancer cells as free fatty acids and had good potential as antitumor substances.

Williams syndrome (WS) is a clinical condition, involving cognitive deficits and an uneven language profile, which has been the object of intense inquiry over the last decades. Although WS results from the hemideletion of around two dozen genes in chromosome 7, no gene has yet been probed to account for, or contribute significantly to, the language problems exhibited by the affected people. In this paper we have relied on gene expression profiles in the peripheral blood of WS patients obtained by microarray analysis and show that several robust candidates for language disorders and/or for language evolution in the species, all of them located outside the hemideleted region, are up- or downregulated in the blood of subjects with WS. Most of these genes play a role in the development and function of brain areas involved in language processing, which exhibit structural and functional anomalies in people with this condition. Overall, these genes emerge as robust candidates for language dysfunction in WS.