Mesenchymal Stem Cells Promote Polarization of M2 Macrophages in Mice with Acute-On-Chronic Liver Failure via Mertk/JAK1/STAT6 Signaling.

Acute-on-chronic liver failure (ACLF) is a severe disease with a high mortality. Macrophage-related inflammation plays a crucial role in ACLF development. Mesenchymal stem cells (MSCs) treatment was demonstrated to be beneficial in ACLF in our previous study; however, the underlying mechanisms remain unknown. Therefore, mouse bone marrow-derived MSCs were used to treat an ACLF mouse model or cocultured with RAW264.7/J774A.1 macrophages that were stimulated with LPS. Histological and serological parameters and survival were analyzed to evaluate efficacy. We detected changes of Mer tyrosine kinase (Mertk), JAK1/STAT6, inflammatory cytokines, and markers of macrophage polarization in vitro and in vivo. In ACLF mice, MSCs improved liver function and 48-h survival of ACLF mice and alleviated inflammatory injury by promoting M2 macrophage polarization and elevated Mertk expression levels in macrophages. This is significant, as Mertk regulates M2 macrophage polarization via the JAK1/STAT6 signaling pathway.

Comprehensive assessment of fine motor movement and cognitive function among older adults in China: a cross-sectional study.

BACKGROUND: Fine motor skills are closely related to cognitive function. However, there is currently no comprehensive assessment of fine motor movement and how it corresponds with cognitive function. To conduct a complete assessment of fine motor and clarify the relationship between various dimensions of fine motor and cognitive function. METHODS: We conducted a cross-sectional study with 267 community-based participants aged ≥ 60 years in Beijing, China. We assessed four tests performance and gathered detailed fine motor indicators using Micro-Electro-Mechanical System (MEMS) motion capture technology. The wearable MEMS device provided us with precise fine motion metrics, while Chinese version of the Montreal Cognitive Assessment (MoCA) was used to assess cognitive function. We adopted logistic regression to analyze the relationship between fine motor movement and cognitive function. RESULTS: 129 (48.3%) of the participants had cognitive impairment. The vast majority of fine motor movements have independent linear correlations with MoCA-BJ scores. According to logistic regression analysis, completion time in the Same-pattern tapping test (OR = 1.033, 95%CI = 1.003-1.063), Completion time of non-dominant hand in the Pieces flipping test (OR = 1.006, 95%CI = 1.000-1.011), and trajectory distance of dominant hand in the Pegboard test (OR = 1.044, 95%CI = 1.010-1.068), which represents dexterity, are related to cognitive impairment. Coordination, represented by lag time between hands in the Same-pattern tapping (OR = 1.663, 95%CI = 1.131-2.444), is correlated with cognitive impairment. Coverage in the Dual-hand drawing test as an important indicator of stability is negatively correlated with cognitive function (OR = 0.709, 95%CI = 0.6501-0.959). Based on the above 5-feature model showed consistently high accuracy and sensitivity at the MoCA-BJ score (ACU = 0.80-0.87). CONCLUSIONS: The results of a comprehensive fine-motor assessment that integrates dexterity, coordination, and stability are closely related to cognitive functioning. Fine motor movement has the potential to be a reliable predictor of cognitive impairment.

Vitamin D is involved in the regulation of Cl- uptake in zebrafish (Danio rerio).

Cl- is a major anion in the bodily fluids of vertebrates, and maintaining its homeostasis is essential for normal physiological functions. Fishes inhabiting freshwater (FW) passively lose body fluid ions, including Cl-, to the external environment because of the electrochemical gradient of ions across the body surface. Therefore, FW fishes have to actively absorb Cl- from the surroundings to maintain ion homeostasis in their bodily fluids. Hormonal control is vital for modulating ion uptake in fish. Vitamin D is involved in the regulation of Ca2+ uptake and acid secretion in fish. In the present study, we found that the levels of bioactive vitamin D, 1α,25-dihydroxyvitamin D3 (1α,25(OH)2D3), significantly increased in zebrafish embryos and adults after exposure to water containing low levels of Cl-. Moreover, the administration of 1α,25(OH)2D3 treatment (20 µg/L) in zebrafish embryos, and intraperitoneal (i.p.) injection of 1α,25(OH)2D3 (5 µg/kg body mass) in zebrafish adults, resulting the increased Cl- content in bodily fluid in zebrafish. Na+-Cl- cotransporter 2b (NCC2b) and Cl- channel 2c (CLC2c) are specifically expressed during Cl- uptake by ionocytes in zebrafish. Our results indicated that the mRNA and protein expression of NCC2b and CLC2c considerably increased in the zebrafish with exogenous 1α,25(OH)2D3 treatment. Additionally, exogenous 1α,25(OH)2D3 administration increased the number of NCC2b- and CLC2c-expressing cells in yolk skins of zebrafish embryos and the gill filaments of zebrafish adults. Transcript signals of vitamin D receptors (VDRs) were identified in NCC2b-expressing cells. Knockdown of VDRa and VDRb significantly reduced the expression of NCC2b and CLC2c and the number of NCC2b- and CLC2c-expressing cells. These results indicate that vitamin D can affect Cl- uptake in zebrafish and extend our knowledge of the role of vitamin D in fish physiology.

Mesenchymal stem cell-regulated miRNA-mRNA landscape in acute-on-chronic liver failure.

BACKGROUND: Acute-on-chronic liver failure (ACLF) is a major challenge in the field of hepatology. While mesenchymal stem cell (MSC) therapy can improve the prognosis of patients with ACLF, the molecular mechanisms through which MSCs attenuate ACLF remain poorly understood. We performed global miRNA and mRNA expression profiling via next-generation sequencing of liver tissues from MSC-treated ACLF mice to identify important signaling pathways and major factors implicated in ACLF alleviation by MSCs. METHODS: Carbon tetrachloride-induced ACLF mice were treated with saline or mouse bone marrow-derived MSCs. Mouse livers were subjected to miRNA and mRNA sequencing. Related signal transduction pathways were obtained through Gene Set Enrichment Analysis. Functional enrichment, protein-protein interaction, and immune infiltration analyses were performed for the differentially expressed miRNA target genes (DETs). Hub miRNA and mRNA associated with liver injury were analyzed using LASSO regression. The expression levels of hub genes were subjected to Pearson's correlation analysis and verified using RT-qPCR. The biological functions of hub genes were verified in vitro. RESULTS: The tricarboxylic acid cycle and peroxisome proliferator-activated receptor pathways were activated in the MSC-treated groups. The proportions of liver-infiltrating NK resting cells, M2 macrophages, follicular helper T cells, and other immune cells were altered after MSC treatment. The expression levels of six miRNAs and 10 transcripts correlated with the degree of liver injury. miR-27a-5p was downregulated in the mouse liver after MSC treatment, while its target gene E2f2 was upregulated. miR-27a-5p inhibited E2F2 expression, suppressed G1/S phase transition and proliferation of hepatocytes, in addition to promoting their apoptosis. CONCLUSIONS: This is the first comprehensive analysis of miRNA and mRNA expression in the liver tissue of ACLF mice after MSC treatment. The results revealed global changes in hepatic pathways and immune subpopulations. The miR-27a-5p/E2F2 axis emerged as a central regulator of the MSC-induced attenuation of ACLF. The current findings improve our understanding of the molecular mechanisms through which MSCs alleviate ACLF.

[Pseudomonas Aeruginosa Affects the Function of Pulmonary Vascular Endothelial Cells].

Objective To investigate the impact of Pseudomonas aeruginosa(PA) infection on the function of pulmonary vascular endothelial cells,and explore the mechanism of this bacterium in exacerbating lung inflammation in mice. Methods Two hours after human lung microvascular endothelial cell(HULEC-5a) were infected with the PA strain PAO1,the mRNA levels of autophagy-related gene 5(ATG5),6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3(PFKFB3),and calcium adhesion protein 5(CDH5) were determined by reverse transcription real-time fluorescent quantitative PCR(RT-qPCR).The protein levels of ATG5,PFKFB3,and vascular endothelial calcium adhesion protein(VE-cadherin) were detected by immunofluorescence.After the expression of ATG5 and PFKFB3 was respectively knocked down by small interfering RNA(siRNA),RT-qPCR was employed to measure the mRNA levels of ATG5,PFKFB3,and CDH5,and immunofluorescence to detect the protein levels of PFKFB3 and VE-cadherin.In addition,the lactate assay kit was used to determine the level of lactate in the cells.After mice were infected with PAO1,lung inflammation was assessed through histopathological section staining.Confocal microscopy was employed to capture and analyze fluorescence-labeled PFKFB3 and VE-cadherin in endothelial cells. Results Compared with the control group,the HULEC-5a cells infected with PAO1 showed up-regulated mRNA and protein levels of PFKFB3(all P<0.05),down-regulated mRNA level of CDH5(P=0.023),disrupted continuity and down-regulated protein level of VE-cadherin(P<0.001),and elevated lactate level(P=0.017).Compared with PAO1-infected HULEC-5a cells,knocking down PFKFB3 led to the up-regulated mRNA level of CDH5(P=0.043),lowered lactate level(P=0.047),and restored continuity of VE-cadherin;knocking down ATG5 led to up-regulated mRNA and protein levels of PFKFB3(P=0.013 and P=0.003),elevated lactate level(P=0.015),and down-regulated mRNA level of CDH5(P=0.020) and protein level of VE-cadherin(P=0.001).The HE staining results showed obvious red blood cell leakage,inflammatory cell infiltration,alveolar septal widening,and partial detachment of vascular endothelial cells in the alveoli of PA-infected mice.Immunofluorescence staining showed up-regulated expression of PFKFB3 and decreased fluorescence signal of VE-cadherin in endothelial cells of infected mice compared with normal mice. Conclusion PA may regulate the PFKFB3 pathway via AGT5 to disrupt the function of pulmonary vascular endothelial cells,thereby exacerbating the inflammation in the lungs of mice.

Cerebral Microbleeds in Fragile X-Associated Tremor/Ataxia Syndrome.

BACKGROUND: Fragile X-associated tremor/ataxia syndrome is a neurodegenerative disease of late onset developed by carriers of the premutation in the fragile x mental retardation 1 (FMR1) gene. Pathological features of neurodegeneration in fragile X-associated tremor/ataxia syndrome include toxic levels of FMR1 mRNA, ubiquitin-positive intranuclear inclusions, white matter disease, iron accumulation, and a proinflammatory state. OBJECTIVE: The objective of this study was to analyze the presence of cerebral microbleeds in the brains of patients with fragile X-associated tremor/ataxia syndrome and investigate plausible causes for cerebral microbleeds in fragile X-associated tremor/ataxia syndrome. METHODS: We collected cerebral and cerebellar tissue from 15 fragile X-associated tremor/ataxia syndrome cases and 15 control cases carrying FMR1 normal alleles. We performed hematoxylin and eosin, Perls and Congo red stains, ubiquitin, and amyloid ß protein immunostaining. We quantified the number of cerebral microbleeds, amount of iron, presence of amyloid ß within the capillaries, and number of endothelial cells containing intranuclear inclusions. We evaluated the relationships between pathological findings using correlation analysis. RESULTS: We found intranuclear inclusions in the endothelial cells of capillaries and an increased number of cerebral microbleeds in the brains of those with fragile X-associated tremor/ataxia syndrome, both of which are indicators of cerebrovascular dysfunction. We also found a suggestive association between the amount of capillaries that contain amyloid ß in the cerebral cortex and the rate of disease progression. CONCLUSION: We propose microangiopathy as a pathologic feature of fragile X-associated tremor/ataxia syndrome. © 2021 International Parkinson and Movement Disorder Society.

Resveratrol restores sensitivity of glioma cells to temozolamide through inhibiting the activation of Wnt signaling pathway.

Malignant gliomas are aggressive primary neoplasms that originate in the glial cells of the brain or the spine with notable resistance to standard treatment options. We carried out the study with the aim to shed light on the sensitization of resveratrol to temozolomide (TMZ) against glioma through the Wnt signaling pathway. Initially, glioma cell lines with strong resistance to TMZ were selected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Then, the glioma cells were subjected to resveratrol, TMZ, Wnt signaling pathway inhibitors, and activators. Cell survival rate and inhibitory concentration at half maximum value were detected by MTT, apoptosis by flow cytometry, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling staining, in vitro proliferation by hanging drop method and ß-catenin translocation into nuclei by TOP/FOP-FLASH assay. The expressions of the Wnt signaling pathway-related and apoptosis-related factors were determined by western blot analysis. Nude mice with glioma xenograft were established to detect tumorigenic ability. Glioma cell lines T98G and U138 which were highly resistant to TMZ were selected for subsequent experiments. Resveratrol increased the efficacy of TMZ by restraining cell proliferation, tumor growth, and promoting cell apoptosis in glioma cells. Resveratrol inhibited Wnt2 and ß-catenin expressions yet elevated GSK-3ß expression. Moreover, the Wnt signaling pathway participates in the sensitivity enhancing of resveratrol to TMZ via regulating O 6 -methylguanine-DNA methyltransferase (MGMT) expression. Resveratrol sensitized TMZ-induced glioma cell apoptosis by repressing the activation of the Wnt signaling pathway and downregulating MGMT expression, which may confer new thoughts to the chemotherapy of glioma.

The red bayberry genome and genetic basis of sex determination.

Morella rubra, red bayberry, is an economically important fruit tree in south China. Here, we assembled the first high-quality genome for both a female and a male individual of red bayberry. The genome size was 313-Mb, and 90% sequences were assembled into eight pseudo chromosome molecules, with 32 493 predicted genes. By whole-genome comparison between the female and male and association analysis with sequences of bulked and individual DNA samples from female and male, a 59-Kb region determining female was identified and located on distal end of pseudochromosome 8, which contains abundant transposable element and seven putative genes, four of them are related to sex floral development. This 59-Kb female-specific region was likely to be derived from duplication and rearrangement of paralogous genes and retained non-recombinant in the female-specific region. Sex-specific molecular markers developed from candidate genes co-segregated with sex in a genetically diverse female and male germplasm. We propose sex determination follow the ZW model of female heterogamety. The genome sequence of red bayberry provides a valuable resource for plant sex chromosome evolution and also provides important insights for molecular biology, genetics and modern breeding in Myricaceae family.

The effect of AP-2δ on transcription of the Prestin gene in HEI-OC1 cells upon oxidative stress.

BACKGROUND: The study aimed to investigate the effect of oxidative stress on Prestin expression, and explore the transcription factors (TFs) that are involved in regulating the expression of Prestin in House Ear Institute-Organ of Corti 1 (HEI-OC1) cells upon oxidative stress. METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were used to detect the expression level of Prestin. Reverse chromatin immunoprecipitation (reverse ChIP) assay was performed to identify proteins that could bind to the Prestin gene. Small interfering RNA (siRNA) and chromatin immunoprecipitation (ChIP) experiments were used to further verify the results. HEI-OC1 cells were incubated with four different concentrations of tert-butyl hydroperoxide (t-BHP) for 24 h or 48 h to construct the oxidative stress model. RESULTS: Oxidative stress induced Prestin increase at the mRNA level but with a concomitant decrease at the protein level. TF activating enhancer binding protein-2δ (AP-2δ) screened by reverse ChIP assay was demonstrated to bind to transcriptional start site 1441 of the Prestin promoter region and negatively regulate the expression of Prestin by siRNA and ChIP experiments. Furthermore, AP-2δ was down-regulated under oxidative stress. CONCLUSIONS: In conclusion, oxidative stress inhibits the expression of Prestin protein, and the transcription mechanism is triggered to compensate for the loss of Prestin protein. AP-2δ is one of the important TFs that suppresses transcription of the Prestin gene, and AP-2δ suppression further boosted Prestin mRNA activation under oxidative stress.

Down-regulation of the long noncoding RNA-HOX transcript antisense intergenic RNA inhibits the occurrence and progression of glioma.

This study aims to explore the role of long noncoding RNA (lncRNA)-HOX transcript antisense intergenic RNA (HOTAIR) in the occurrence and progression of glioma. Fresh glioma and normal brain tissues were classified into a glioma group (n = 67) and a normal group (n = 64) respectively. U87 cells were assigned into the blank, sh-NC, and sh-HOTAIR groups. Quantitative real-time polymerase chain reaction (qRT-PCR) was utilized to determine HOTAIR expression. Cell proliferation, cell cycle and cell apoptosis rates were detected by cell counting kit-8 (CCK-8) and flow cytometry (FCM). Scratch test and transwell assay were conducted for cell migration and invasion. Orthotopic glioma tumor model in nude mice was established by inoculating tumor cell suspension. Hematoxylin-Eosin (HE) staining was used to observe the growth and invasion of orthotopic glioma tumors. The expression of HOTAIR and cell viability was found to be lowest in the sh-HOTAIR group among the three groups. The sh-HOTAIR group exhibited a higher apoptotic rate and lower number of cell migration compared with the blank and sh-NC groups. Additionally, the speed of wound healing was slower, the migration distance decreased and the survival time of nude mice was extended in the sh-HOTAIR compared to the other groups. Moreover, the sh-HOTAIR group demonstrated reduced lesion sizes and inflammation, no convulsions or hemiplegia and lesser number of satellite metastases. Our findings support that down-regulation of HOTAIR could inhibit cell proliferation, promote cell apoptosis as well as suppress cell invasion and migration in the progression of glioma.

Emergency Pacing via the Umbilical Vein and Subsequent Permanent Pacemaker Implantation in a Neonate.

A dying neonate with congenital complete atrioventricular block underwent an emergency temporary pacing via the umbilical vein 1 h after birth. Implantation of a permanent epicardial pacemaker system was performed at the age of 10 days. During the follow-up period of 3 months, the child had been growing well with the VVIR pacemaker.

Single-locus enrichment without amplification for sequencing and direct detection of epigenetic modifications.

A gene-level targeted enrichment method for direct detection of epigenetic modifications is described. The approach is demonstrated on the CGG-repeat region of the FMR1 gene, for which large repeat expansions, hitherto refractory to sequencing, are known to cause fragile X syndrome. In addition to achieving a single-locus enrichment of nearly 700,000-fold, the elimination of all amplification steps removes PCR-induced bias in the repeat count and preserves the native epigenetic modifications of the DNA. In conjunction with the single-molecule real-time sequencing approach, this enrichment method enables direct readout of the methylation status and the CGG repeat number of the FMR1 allele(s) for a clonally derived cell line. The current method avoids potential biases introduced through chemical modification and/or amplification methods for indirect detection of CpG methylation events.

Insights into salt tolerance from the genome of Thellungiella salsuginea.

Thellungiella salsuginea, a close relative of Arabidopsis, represents an extremophile model for abiotic stress tolerance studies. We present the draft sequence of the T. salsuginea genome, assembled based on ~134-fold coverage to seven chromosomes with a coding capacity of at least 28,457 genes. This genome provides resources and evidence about the nature of defense mechanisms constituting the genetic basis underlying plant abiotic stress tolerance. Comparative genomics and experimental analyses identified genes related to cation transport, abscisic acid signaling, and wax production prominent in T. salsuginea as possible contributors to its success in stressful environments.

Double charge transfer processes enable a green multiple resonance-induced thermally activated delayed fluorescence emitter for an efficient narrowband OLED.

Benefitting from short-range charge transfer (SR-CT) and through-space charge transfer (TSCT) effects, an efficient green narrowband emitter, BNDCN, was developed. Owing to the synergistic effect of double CT processes, a BNDCN-based organic light-emitting diode showed a high external quantum efficiency of 32.3%.

Enlarged perivascular spaces and their association with motor, cognition, MRI markers and cerebrovascular risk factors in male fragile X premutation carriers.

FMR1 premutation carriers (55-200 CGG repeats) are at risk of developing fragile X-associated tremor/ataxia syndrome (FXTAS), a neurodegenerative disorder associated with motor and cognitive impairment. Bilateral hyperintensities of the middle cerebellar peduncles (MCP sign) are the major radiological hallmarks of FXTAS. In the general population, enlarged perivascular spaces (PVS) are biomarkers of small vessel disease and glymphatic dysfunction and are associated with cognitive decline. Our aim was to determine if premutation carriers show higher ratings of PVS than controls and whether enlarged PVS are associated with motor and cognitive impairment, MRI features of neurodegeneration, cerebrovascular risk factors and CGG repeat length. We evaluated 655 MRIs (1-10 visits/participant) from 229 carriers (164 with FXTAS and 65 without FXTAS) and 133 controls. PVS in the basal ganglia (BG-EPVS), centrum semiovale, and midbrain were evaluated with a semiquantitative scale. Mixed-effects models were used for statistical analysis adjusting for age. In carriers with FXTAS, we revealed that (1) BG-PVS ratings were higher than those of controls and carriers without FXTAS; (2) BG-PVS severity was associated with brain atrophy, white matter hyperintensities, enlarged ventricles, FXTAS stage and abnormal gait; (3) age-related increase in BG-PVS was associated with cognitive dysfunction; and (4) PVS ratings of all three regions showed robust associations with CGG repeat length and were higher in carriers with the MCP sign than carriers without the sign. This study demonstrates clinical relevance of PVS in FXTAS especially in the basal ganglia region and suggests microangiopathy and dysfunctional cerebrospinal fluid circulation in FXTAS physiopathology.

Hybridization of short-range and long-range charge transfer boosts room-temperature phosphorescence performance.

At present, mainstream room-temperature phosphorescence (RTP) emission relies on organic materials with long-range charge-transfer effects; therefore, exploring new forms of charge transfer to generate RTP is worth studying. In this work, indole-carbazole was used as the core to ensure the narrowband fluorescence emission of the material based on its characteristic short-range charge-transfer effect. In addition, halogenated carbazoles were introduced into the periphery to construct long-range charge transfer, resulting in VTCzNL-Cl and VTCzNL-Br. By encapsulating these phosphors into a robust host (TPP), two host-guest crystalline systems were further developed, achieving efficient RTP performance with phosphorescence quantum yields of 26% and phosphorescence lifetimes of 3.2 and 39.2 ms, respectively.

Isoindoline-based fluorogenic probes bearing a self-immolative linker for the sensitive and selective detection of O-GlcNAcase activity.

O-GlcNAcase (OGA) is implicated in several important biological and disease-relevant processes. Here, we synthesized fluorogenic probes for OGA by grafting GlcNAc directly or using a self-immolative linker to the hydroxyl position of 4-hydroxylisoindoline (BHID), a typical excited-state intramolecular proton transfer (ESIPT) probe. The probe was used for a fluorogenic assay to determine the half maximal inhibitory concentration of a known OGA inhibitor and differentiate between OGA and hexosaminidase when GlcNAc is replaced by GlcNPr, where a propionyl group is used instead of an acetyl group.

Association Between Long-Term Exposure to Ambient Air Pollution and the Risk of Mild Cognitive Impairment in a Chinese Urban Area: A Case-Control Study.

Background: As a prodromal stage of dementia, significant emphasis has been placed on the identification of modifiable risks of mild cognitive impairment (MCI). Research has indicated a correlation between exposure to air pollution and cognitive function in older adults. However, few studies have examined such an association among the MCI population inChina. Objective: We aimed to explore the association between air pollution exposure and MCI risk from the Hubei Memory and Aging Cohort Study. Methods: We measured four pollutants from 2015 to 2018, 3 years before the cognitive assessment of the participants. Logistic regression models were employed to calculate odds ratios (ORs) to assess the relationship between air pollutants and MCI risk. Results: Among 4,205 older participants, the adjusted ORs of MCI risk for the highest quartile of PM2.5, PM10, O3, and SO2 were 1.90 (1.39, 2.62), 1.77 (1.28, 2.47), 0.56 (0.42, 0.75), and 1.18 (0.87, 1.61) respectively, compared with the lowest quartile. Stratified analyses indicated that such associations were found in both males and females, but were more significant in older participants. Conclusions: Our findings are consistent with the growing evidence suggesting that air pollution increases the risk of mild cognitive decline, which has considerable guiding significance for early intervention of dementia in the older population. Further studies in other populations and broader geographical areas are warranted to validate these findings.

Molecular footprints of domestication and improvement in soybean revealed by whole genome re-sequencing.

BACKGROUND: Artificial selection played an important role in the origin of modern Glycine max cultivars from the wild soybean Glycine soja. To elucidate the consequences of artificial selection accompanying the domestication and modern improvement of soybean, 25 new and 30 published whole-genome re-sequencing accessions, which represent wild, domesticated landrace, and Chinese elite soybean populations were analyzed. RESULTS: A total of 5,102,244 single nucleotide polymorphisms (SNPs) and 707,969 insertion/deletions were identified. Among the SNPs detected, 25.5% were not described previously. We found that artificial selection during domestication led to more pronounced reduction in the genetic diversity of soybean than the switch from landraces to elite cultivars. Only a small proportion (2.99%) of the whole genomic regions appear to be affected by artificial selection for preferred agricultural traits. The selection regions were not distributed randomly or uniformly throughout the genome. Instead, clusters of selection hotspots in certain genomic regions were observed. Moreover, a set of candidate genes (4.38% of the total annotated genes) significantly affected by selection underlying soybean domestication and genetic improvement were identified. CONCLUSIONS: Given the uniqueness of the soybean germplasm sequenced, this study drew a clear picture of human-mediated evolution of the soybean genomes. The genomic resources and information provided by this study would also facilitate the discovery of genes/loci underlying agronomically important traits.

Influence of the fragile X mental retardation (FMR1) gene on the brain and working memory in men with normal FMR1 alleles.

The fragile X mental retardation 1 (FMR1) gene plays an important role in the development and maintenance of neuronal circuits that are essential for cognitive functioning. We explored the functional linkage(s) among lymphocytic FMR1 gene expression, brain structure, and working memory in healthy adult males. We acquired T1-weighted and diffusion tensor imaging from 37 males (18-80 years, mean ± SD= 40.7 ± 17.3 years) with normal FMR1 alleles and performed genetic and working memory assessments. Brain measurements were obtained from fiber tracts important for working memory (i.e. the arcuate fasciculus, anterior cingulum bundle, inferior longitudinal fasciculus, and the genu and anterior body of the corpus callosum), individual voxels, and whole brain. Both FMR1 mRNA and protein (FMRP) levels exhibited significant associations with brain measurements, with FMRP correlating positively with gray matter volume and white matter structural organization, and FMR1 mRNA negatively with white matter structural organization. The correlation was widespread, impacting rostral white matter and 2 working-memory fiber tracts for FMRP, and all cerebral white matter areas except the fornix and cerebellar peduncles and all 4 fiber tracts for FMR1 mRNA. In addition, the levels of FMR1 mRNA as well as the fiber tracts demonstrated a significant correlation with working memory performance. While FMR1 mRNA exhibited a negative correlation with working memory, fiber tract structural organization showed a positive correlation. These findings suggest that the FMR1 gene is a genetic factor common for both working memory and brain structure, and has implications for our understanding of the transmission of intelligence and brain structure.