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The cyclic GMP-AMP synthase and stimulator of interferon (IFN) genes (cGAS-STING) pathway serves as a crucial component of innate immune defense and exerts immense antiviral activity by inducing the expression of type I IFNs. Currently, STING-activated production of type I IFNs has been thought to be mediated only by TANK-binding kinase 1 (TBK1). Here, we identified that porcine IKKe (pIKKe) is also directly involved in STING-induced type I IFN expression and antiviral response by using IKKe -/- porcine macrophages. Similar to pTBK1, pIKKe interacts directly with pSTING on the C-terminal tail. Furthermore, the TBK1-binding motif of pSTING C-terminal tail is essential for its interaction with pIKKe, and within the TBK1-binding motif, the leucine (L) 373 is also critical for the interaction. On the other hand, both kinase domain and scaffold dimerization domain of pIKKe participate in the interactions with pSTING. Consistently, the reconstitution of pIKKe and its mutants in IKKe -/- porcine macrophages corroborated that IKKe and its kinase domain and scaffold dimerization domain are all involved in the STING signaling and antiviral function. Thus, our findings deepen the understanding of porcine cGAS-STING pathway, which lays a foundation for effective antiviral therapeutics against porcine viral diseases. [ABSTRACT FROM AUTHOR]

Liver ischemia reperfiision (IR) injury induces hepatic stellate cell (HSC) activation and liver fibrosis. Propofol (PRO) possesses a positive protective effect on liver ischemia reperfusion injury. We aimed to investigate PRO function and mechanism in IR-induced liver fibrosis. A mice model of liver IR was established. Hematoxylin-eosin (HE) staining was utilized to evaluate liver tissue's pathological changes. Masson staining was applied to evaluate liver fibrosis. The expression level of a-SMA was measured by immunohistochemical (IHC). The expressions of IncRNA HOXA11-AS (HOXA11- AS), PTBP1, HDAC4, α-SMA, COL1A1 and Fibronectin were tested by qRT-PCR or Western blot. The commercial kits detected alanine aminotransferase (ALT) and aspartate aminotransferase (AST) concentrations in serum. Enzyme-linked immunosorbent assay (ELISA) measured TNF-α and IL-6 levels. The binding relationship between HOXA11-AS, PTBP1 and HDAC4 was verified by RNA immunoprecipitAtion (RIP). Our results showed that PRO alleviated liver fibrosis and the inflammation in IR-induced mice. PRO decreased the expression levels of HOXA11-AS, PTBP1 and HDAC4. Furthermore, HOXA11-AS overexpression abolished the protective effect of PRO against liver fibrosis in mice with IR-disposed. HOXA11-AS interacted with PTBP1 to regulate HDAC4 level and prevented its degradation in JS-1 cells. HDAC4 silencing eliminated the regulatory of HOXA11-AS overexpression on fibrosis and inflammation in IR-induced mice PRO inhibited HOXA11-AS expression to regulate HDAC4, thereby influencing liver fibrosis and inflammation induced by IR. It suggesting that PRO plays a protective role in liver fibrosis induced by ischemia-reperfusion in mice by regulating HOXA11-AS/PTBP1/HDAC4 axis. [ABSTRACT FROM AUTHOR]

The fall armyworm (FAW) Spodoptera frugiperda is a major polyphagous pest that feeds mainly on food crops, such as corn and rice, posing a serious threat to the safety of food crops worldwide. Trehalase, can degrade trehalose and the resulting products participate in the synthesis of chitin, one of the main components of outer epidermis in insects. Therefore, trehalase inhibitors have been identified as novel agents for pest control. We report the insecticidal potential of a trehalase inhibitor validamycin against FAW. Validamycin (1 µg/µL) when injected in FAW using microinjection could significantly reduce trehalase activity 48 h later, especially, the activity of soluble trehalase, then the glucose content and glycogen content also decrease. In addition, the deaths of larvae in validamycin treated group at each instar stage were higher than those in the control group, moreover, validamycin treatment increased the pupal weight and prolonged pest development. Similarly, validamycin also significantly inhibited the chitinase activity and caused the accumulation of chitin in FAW. Results of qRT-PCR showed that the expression levels of two trehalose genes (SfTRE1 and SfTRE2), which encode key enzymes in chitin biosynthesis pathway, were significantly reduced, while the expression levels of fructose-6-phosphate transaminase, glucosamine-phosphate N-acetyltransferase and chitinase genes were significantly increased. It is obvious that validamycin has an influence on physiological metabolism and development of FAW, the results obtained will be conducive to the prevention and control of FAW in the future. [ABSTRACT FROM AUTHOR]

Dalbergia tonkinensis is very similar to Dalbergia odorifera in material, texture, and other macroscopic characteristics, and a comparison of the commonalities and differences in the chemical composition of the extractives may help to distinguish the two. However, the chemical composition of Dalbergia tonkinensis heartwood is unknown. The total flavonoid content of Dalbergia tonkinensis heartwood was determined to range between 49.67 to 101.95 mg, which indicated that Dalbergia tonkinensis is as equally rich in flavonoids as Dalbergia odorifera. Thirtyone flavonoids were identified via ultra-performance liquid chromatography-mass spectrometry in Dalbergia tonkinensis. Among them, the contents of 15 medicinal active flavonoids with were determined, and the liquiritigenin, naringenin, formononetin, pinocembrin, and biochanin A contents were found to be high. The 12 volatile compositions of Dalbergia tonkinensis heartwood identified via gas chromatographymass spectrometry were very similar to those of Dalbergia odorifera and were dominated by trans-nerolidol, caryophyllene oxide, and eudesmol. The relationship between the chemical composition of Dalbergia tonkinensis and Dalbergia odorifera heartwood extracts was determined via a principal component analysis, and the results indicated that there was no significant difference in chemical composition between the two. This suggested that Dalbergia tonkinensis could be used as a potential substitute for Dalbergia odorifera. [ABSTRACT FROM AUTHOR]

Heat shock protein (HSP) 40 has emerged as a key factor in both innate and adaptive immunity, whereas the role of HLJ1, a molecular chaperone in HSP40 family, in modulating endotoxin-induced sepsis severity is still unclear. During lipopolysaccharide (LPS)-induced endotoxic shock, HLJ1 knockout mice shows reduced organ injury and IFN-γ (interferon-γ)-dependent mortality. Using single-cell RNA sequencing, we characterize mouse liver nonparenchymal cell populations under LPS stimulation, and show that HLJ1 deletion affected IFN-γ-related gene signatures in distinct immune cell clusters. In CLP models, HLJ1 deletion reduces IFN-γ expression and sepsis mortality rate when mice are treated with antibiotics. HLJ1 deficiency also leads to reduced serum levels of IL-12 in LPS-treated mice, contributing to dampened production of IFN-γ in natural killer cells but not CD4+ or CD8+ T cells, and subsequently to improved survival rate. Adoptive transfer of HLJ1-deleted macrophages into LPS-treated mice results in reduced IL-12 and IFN-γ levels and protects the mice from IFN-γ-dependent mortality. In the context of molecular mechanisms, HLJ1 is an LPS-inducible protein in macrophages and converts misfolded IL-12p35 homodimers to monomers, which maintains bioactive IL-12p70 heterodimerization and secretion. This study suggests HLJ1 causes IFN-γ-dependent septic lethality by promoting IL-12 heterodimerization, and targeting HLJ1 has therapeutic potential in inflammatory diseases involving activated IL-12/IFN-γ axis. [ABSTRACT FROM AUTHOR]

Objective: Investigation of muscle growth at different developmental stages is an appropriate strategy for studying the mechanisms underlying muscle development and differences in phenotypes. In particular, the muscle development mechanisms and the difference between the fastest and slowest growth rates. Methods: In this study, we used a growth curve model to fit the growth inflection point (IP) of QingYu pigs and compared differences in the long non-coding RNA (lncRNA) transcriptome of muscle both at the growth IP and plateau phase (PP). Results: The growth curve of the QingYu pig had a good fit (R2 = 0.974) relative to a typical S-curve and reached the IP at day 177.96. At the PP, marbling, intramuscular fat, and monounsaturated fatty acids had increased significantly and the percentage of lean muscle and polyunsaturated fatty acids had decreased. A total of 1,199 mRNAs and 62 lncRNAs were differentially expressed at the IP compared with the PP. Additional to gene ontology and Kyoto encyclopedia of genes and genomes pathway analyses, these differentially expressed protein coding genes were principally related to muscle growth and lipid metabolism. Conclusion: Our results suggest that the identified differentially expressed lncRNAs, could play roles in muscle growth, fat deposition and regulation of fatty acid composition at the IP and PP. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is one of the most common tumors worldwide and is associated with high mortality. Here we performed bioinformatics analysis, which we validated using immunohistochemistry in order to search for hub genes that might serve as biomarkers or therapeutic targets in CRC. Based on data fromThe Cancer Genome Atlas (TCGA), we identified 4832 genes differentially expressed between CRC and normal samples (1562 up-regulated and 3270 down-regulated in CRC). Gene ontology (GO) analysis showed that up-regulated genes were enriched mainly in organelle fission, cell cycle regulation, and DNA replication; down-regulated genes were enriched primarily in the regulation of ion transmembrane transport and ion homeostasis. Weighted gene co-expression network analysis (WGCNA) identified eight gene modules that were associated with clinical characteristics of CRC patients, including brown and blue modules that were associated with cancer onset. Analysis of the latter two hub modules revealed the following six hub genes: adhesion G protein-coupled receptor B3 (BAI3, also known as ADGRB3), cyclin F (CCNF), cytoskeleton-associated protein 2 like (CKAP2L), diaphanous-related formin 3 (DIAPH3), oxysterol binding protein-like 3 (OSBPL3), and RERG-like protein (RERGL). Expression levels of these hub genes were associated with prognosis, based on Kaplan-Meier survival analysis of data from the Gene Expression Profiling Interactive Analysis database. Immunohistochemistry of CRC tumor tissues confirmed that OSBPL3 is up-regulated in CRC. Our findings suggest that CCNF, DIAPH3, OSBPL3, and RERGL may be useful as therapeutic targets against CRC. BAI3 and CKAP2L may be novel biomarkers of the disease. [ABSTRACT FROM AUTHOR]

Ultrafine face‐centered cubic (fcc) ruthenium nanoclusters (NCs) are of great interest due to their super high catalytic activity. However, it is extremely difficult to prepare ≈1 nm fcc ruthenium NCs with high energy atoms due to their easy aggregation. Herein, the nucleation process of ruthenium centers by confined pyrolysis of a multivariate metal–organic framework to isolate ultrafine fcc NCs (from single atom to 1.33 nm) via in situ formed stabilizers is unveiled. Systematic investigations demonstrate that preferential nucleation of Ru single atoms to fcc clusters in the initial nucleation represents a key step and makes it possible to separate ultrafine fcc Ru NCs with in situ formed N‐doped porous carbon. A record high turnover frequency of 1300.53 min−1 for methanolysis of ammonia borane is achieved by 1.33 nm NCs. This work suggests a new strategy to prepare ultrafine metal NCs by instantly capturing structure‐specific crystal nuclei with in situ formed stabilizers. [ABSTRACT FROM AUTHOR]

Objective: The QingYu pig is well known for its excellent meat quality attributes in Sichuan province, China. In order to improve its production efficiency, the determination of genetic factors contributing to quantifiable economic traits of livestock is important. Moreover, the cross-breeding of QingYu pigs with western breeds possessing strong growth attributes is an efficient way to improve the performance of this breed. Methods: Here, the genetic parameters of several important reproductive traits of QingYu pigs were estimated, include total number born (TNB), number born alive, litter birth weight, individual birth weight, number of piglets weaned, litter weaning weight, and individual weaning weight. The data was analyzed using the ASReml 3.0 software (NSW Inc., Sydney, Australia). Furthermore, the effects of crossing Berkshire with QingYu (BQ) pigs on carcass and meat quality traits, as well as the effects of slaughter weight on carcass and meat quality of BQ were characterized. Results: QingYu pigs exhibited superior reproductive traits. The TNB available to QingYu pigs was more than 8 per parity. The observed repeatability of the reproductive traits of the QingYu pigs was between 0.10 and 0.23. The significantly correlated genetic and phenotypic of reproduction traits were consistent. Interestingly, the BQ pigs exhibited improved carcass quality, with a significant increase in loin muscle area, lean percentage and reduction in sebum percentage. As a result, BQ had higher L45min, lower cooking scores, and lower drip loss. In addition, the loin muscle area, body length, and sebum percentage were significantly higher in 90 and 100 kg animals. Cooking loss showed a significant increase at 80 kg, and marbling increased significantly from 90 kg. Conclusion: The results of this study suggest that QingYu pigs exhibit excellent reproductive properties and heritability of these traits. Crossing with Berkshire is an efficient strategy to improve the carcass and meat quality of QingYu pigs for commercial operations. Furthermore, it appears as though the optimal slaughter weight of BQ pigs is at approximately 90 kg. [ABSTRACT FROM AUTHOR]

In all eukaryotes, a functional mitotic spindle is essential for distributing duplicated chromosomes into daughter cells. Mitotic spindle assembly involves highly ordered arrangement of microtubules (MTs). The Augmin protein complex recruits γ-tubulin ring complex (γ-TuRC) toMTsand thereby promotes MT-based MT nucleation and mitotic spindle assembly. However, several factors that may promote Augmin recruitment to MTs remain unknown. Here, we show that echinoderm microtubule-associated protein-like 3 (EML3), an MT-associated protein, facilitates binding between MTs and Augmin/γ-TuRC and recruiting the latter to MTs for proper mitotic spindle assembly and kinetochore-MT connections. Using immunofluorescence microscopy, live-cell imaging, and immunoprecipitation assays, we found that EML3 recruits Augmin/γ-TuRC to the MTs to enhance MT-based MT nucleation in both spindle and small acentrosomal asters. We also noted that the EML3-mediated recruitment is controlled by cyclin-dependent kinase 1 (CDK1), which phosphorylated EML3 at Thr-881 and promoted its binding to Augmin/γ-TuRC. RNAi-mediated EML3 knockdown in HeLa cells reduced spindle localization of Augmin/γ-TuRC, which resulted in abnormal spindle assembly and caused kinetochore-MT misconnection. The introduction of exogenous WT or a Thr-881 phosphorylation mimic EML3 variant into the EML3 knockdown cells restored normal Augmin/γ-TuRC localization and spindle assembly. The EML3 knockdown also affected the spindle assembly checkpoint, delaying chromosome congression and cell division. Taken together, our results indicate that EML3 regulates mitotic spindle assembly and the kinetochore-MT connection by regulating MT-based MT nucleation and recruiting Augmin/γ-TuRC to MTs. [ABSTRACT FROM AUTHOR]

By anchoring triazole units onto its skeleton, the luminescent sensing properties of a terbium(iii) metal–organic framework could be efficiently improved, including not only an expansion of the scale of analytes such as Fe3+, anions and nitroaromatic molecules, but also enhanced selectivity and sensitivity. [ABSTRACT FROM AUTHOR]

Heavy alcohol consumption has been associated with increased risk of several cancers, including cancer of the colon, rectum, female breast, oral cavity, pharynx, larynx, liver, and esophagus. It appears that alcohol exposure not only promotes carcinogenesis but also enhances the progression and aggressiveness of existing cancers. The molecular mechanisms underlying alcohol tumor promotion, however, remain unclear. Cancer stem cells (CSC), a subpopulation of cancer cells with self-renewal and differentiation capacity, play an important role in tumor initiation, progression, metastasis, recurrence, and therapy resistance. The recent research evidence suggests that alcohol increases the CSC population in cancers, which may underlie alcohol-induced tumor promotion. This review discusses the recent progress in the research of alcohol promotion of CSC and underlying cellular/molecular mechanisms. The review will further explore the therapeutic potential of CSC inhibition in treating alcohol-induced tumor promotion. [ABSTRACT FROM AUTHOR]

The identifiable target effect refers to the preference for helping identified victims and punishing identifiable perpetrators compared with equivalent but unidentifiable counterparts. The identifiable target effect is often attributed to the heightened moral emotions evoked by identified targets. However, the specific neurocognitive processes that mediate and/or modulate this effect remain largely unknown. Here, we combined a third-party punishment game with brain imaging and computational modeling to unravel the neurocomputational underpinnings of the identifiable transgressor effect. Human participants (males and females) acted as bystanders and punished identified or anonymous wrongdoers. Participants were more punitive toward identified wrongdoers than anonymous wrongdoers because they took a vicarious perspective of victims and adopted lower reference points of inequity (i.e., more stringent norms) in the identified context than in the unidentified context. Accordingly, there were larger activity of the ventral anterior insula, more distinct multivariate neural patterns in the dorsal anterior insula and dorsal anterior cingulate cortex, and lower strength between ventral anterior insula and dorsolateral PFC and between dorsal anterior insula and ventral striatum connectivity in response to identified transgressors than anonymous transgressors. These findings implicate the interplay of expectancy violations, emotions, and self-interest in the identifiability effect. Last, individual differences in the identifiability effect were associated with empathic concern/social dominance orientation, activity in the precuneus/cuneus and temporo-parietal junction, and intrinsic functional connectivity of the dorsolateral PFC. Together, our work is the first to uncover the neurocomputational processes mediating identifiable transgressor effect and to characterize psychophysiological profiles modulating the effect. [ABSTRACT FROM AUTHOR]

Dehydroxytrifluoromethylthiolation of alcohols with a Ph3P+CF2CO2-/S8/F- system is described. Difluorocarbene generated from Ph3P+CF2CO2- would readily combine with elemental sulfur to furnish S-CF2. S-CF2 can be considered as a bifunctional intermediate, activating alcohol and providing scaffold for CF3S- formation, thus allowing for the convenient dehydroxytrifluoromethylthiolation of alcohols. [ABSTRACT FROM AUTHOR]

Increased post-translational modification of proteins by SUMO-2/3 is a cytoprotective response against cell stress induced by ischaemia and reperfusion. However, it is still unclear what other cell stressors trigger protein SUMOylation, what mechanisms enhance and maintain the enhanced SUMOylation, and if it is a general protective mediator against other cytotoxic stresses. Here, we show increased levels of SUMOylation and decreased levels of the SUMO deconjugating enzyme SENP3 in PC12 cells treated with the toxic heavy metal cadmium. In addition, SENP3 knockdown reduced cadmium-induced caspase 3 cleavage and cell death in PC12 cells, while SENP3 overexpression enhanced cell death. These results suggest that SENP3 is an important regulator of the cellular response to cadmium stress in PC12 cells. Our findings are consistent with previous reports of decreased SENP3 and increased SUMOylation in ischaemia, and imply that the regulation of SENP3 levels and subsequent changes in SUMOylation could be a cytoprotective mechanism against caspase 3-mediated cell death. [ABSTRACT FROM AUTHOR]

The impacts of different types of El Niño–Southern Oscillation (ENSO) on the interannual negative correlation (seesaw) between the Somali cross-equatorial flow (CEF) and the Maritime Continent (MC) CEF during boreal summer (June–August) are investigated using the ECMWF twentieth-century reanalysis (ERA-20C) dataset and numerical experiments with a global atmospheric model [the Met Office Unified Model global atmosphere, version 6 (UM-GA6)]. The results suggest that ENSO plays a prominent role in governing the CEF-seesaw relation. A high positive correlation (0.86) exists between the MC CEF and Niño-3.4 index and also in the case of eastern Pacific (EP) El Niño, central Pacific (CP) El Niño, EP La Niña, and CP La Niña events. In contrast, a negative correlation (20.35) exists between the Somali CEF and Niño-3.4 index, and this negative relation is significant only in the EP El Niño years. Further, the variation of the MC CEF is highly correlated with the local north–south sea surface temperature (SST) gradient, while the variation of the Somali CEF displays little relation with the local SST gradient. The Somali CEF may be remotely influenced by ENSO. The model results confirm that the EP El Niño plays a major role in causing the weakened Somali CEF via modifying the Walker cell. However, the impact of the EP El Niño on the Somali CEF differs with different seasonal background. It is also found that the interannual CEF seesaw displays a multidecadal change before and after the 1950s, which is linked with the multidecadal strengthening of the intensity of the EP ENSO. [ABSTRACT FROM AUTHOR]

This study investigated the effects of different interplanting practices in Guangxi Eucalyptus plantations on litter decomposition. Through determining the optimum plantation management practices to optimise litter decomposition for maximising vegetation growth and soil quality, results from this study have the potential to provide the scientific grounds to improve Eucalyptus plantation operations. The results are as follows: The 360-day decomposition of the pure Eucalyptus plantation leaf and branch litter was 2.6 and 4.45% higher than that of the Eucalyptus + Elephant grass plantation, and 2.75 and 1.95% lower than that of the Eucalyptus + Mountain tephrosia plantation. The decomposition rate of the leaf litter was faster than that of branch litter in all the three forest stands types, and difference in decomposition rate between leaf and branch litter was 18.9, 17.05 and 19.7%, respectively, for Eucalyptus, Eucalyptus + Elephant grass and Eucalyptus + Mountain tephrosia plantations. The leaf litter decomposition rate in the Elephant grass and Mountain tephrosia plantation was relatively fast, with decomposition constants of 0.84 and 1.06, respectively, and the time for 50 and 95% decomposition the leaf litter was 0.62 and 3.36 a, and 0.43 and 2.60 a, respectively. Decomposition of leaf and branch litter in the Eucalyptus plantations had clear effects on litter nutrient levels. Nutrient immobilisation within leaf and branch litter ranged from 16.28 to 124.68% and nutrient release ranged from 4.22 to 22.21% among all interplanting practices. The litter P content dynamics differed from the other nutrients. The litter K, Ca, and Mg content declined with increasing decomposition time. With interplanting of Eucalyptus trees with herb age, facilitating Eucalyptus litter decomposition and its nutrient return to the soil. These beneficial interplanting effects on Eucalyptus plantations were greater for the Eucalyptus + Mountain tephrosia plantation than the Eucalyptus + Elephant grass plantation. This research will facilitate sustainable forestry development by improving our understanding of the effects of herbage interplanting methods on long-term production in Eucalyptus plantations. [ABSTRACT FROM AUTHOR]

We fitted the spatial distributions of the satellite galaxies in different dark matter halos obtained from an N-body numerical simulation with a triaxial ellipsoid, and then used the axial ratio of the fitting ellipsoid to measure the flatness of that distribution. By comparing the axial ratio distributions under different conditions, we analyzed the effects of different factors on the calculated result, such as the number of sample satellite galaxies, the selection method of sample satellite galaxies, and the normalization on the radial distribution of the sample, then we analyzed the correlation between the minor axis of the fitting ellipsoid and the orientation of the large scale structure where the dark matter halos exist. We found that whether the radial distribution of the sample is normalized will have a rather large influence on the result, and that the minor axis of the fitting ellipsoid of the halo in a large-scale filament structure more tends to be perpendicular to the direction of the filament structure, and the minor axis of the fitting ellipsoid of the halo in a large-scale sheet structure more tends to be parallel to the normal direction of the sheet structure. [ABSTRACT FROM AUTHOR]

Background: Clinical failures singularly targeting amyloid-β pathology indicate a critical need for alternative Alzheimer's disease (AD) therapeutic strategies. The mixed pathology reported in a large population of AD patients demands a multifunctional drug approach. Since activation of cAMP response element binding protein (CREB) plays a crucial role in synaptic strengthening and memory formation, we retooled a clinical drug with known neuroprotective and anti-inflammatory activity to activate CREB, and validated this novel multifunctional drug, NMZ, in 4 different mouse models of AD. Results: NMZ was tested in three mouse models of familial AD and one model of sporadic AD. In 3 Tg hippocampal slices, NMZ restored LTP. In vivo, memory was improved with NMZ in all animal models with robust cognitive deficits. NMZ treatment lowered neurotoxic forms of Aβ in both APP/PS1 and 3 Tg transgenic mice while also restoring neuronal plasticity biomarkers in the 3 Tg mice. In EFAD mice, incorporation of the major genetic AD risk factor, hAPOE4, did not mute the beneficial drug effects. In a novel sporadic mouse model that manifests AD-like pathology caused by accelerated oxidative stress in the absence of any familial AD mutation, oral administration of NMZ attenuated hallmark AD pathology and restored biomarkers of synaptic and neuronal function. Conclusions: The multifunctional approach, embodied by NMZ, was successful in mouse models of AD incorporating Aβ pathology (APP/PS1), tau pathology (3xTg), and APOE4, the major human genetic risk factor for AD (EFAD). The efficacy observed in a novel model of sporadic AD (Aldh2-/-) demonstrates that the therapeutic approach is not limited to rare, familial AD genetic mutations. The multifunctional drug, NMZ, was not designed directly to target Aβ and tau pathology; however, the attenuation of this hallmark pathology suggests the approach to be a highly promising, disease-modifying strategy for AD and mixed pathology dementia. [ABSTRACT FROM AUTHOR]

A new method has been developed for the Cu-catalyzed C-H trifluoromethylation of 3-arylprop-1-ynes for the selective construction of allenic Csp2-CF3 and propargyl Csp3-CF3 bonds. The selective formation of allenic Csp2-CF3 and propargyl Csp3-CF3 bonds can be controlled by modifying the reaction conditions. [ABSTRACT FROM AUTHOR]

Vaterite crystals with a spherical shape were successfully obtained by the addition of aspartic acid (Asp) in the calcium hydroxide (Ca(OH)2)-carbon dioxide reaction system. Crystalline products were characterized by X-ray diffraction, field emission scanning electron microscopy, Fourier transform infrared spectroscopy, Raman spectroscopy, thermogravimetric analysis, and differential scanning calorimetry (TG-DSC). The experimental results indicate that the addition of Asp can inhibit the growth of calcite but promote the formation of vaterite, and the spherical vaterite CaCO3 is gradually dominant along with the increase of Asp. Meanwhile the content of the vaterite phase is prominently influenced by the reaction temperature, and the optimal temperature for vaterite is at 40 °C. It is proposed that vaterite is induced through the intermediate chelated by Asp and Ca(OH)2, and then Asp is adsorbed on the surface of vaterite by chelation, preventing the metastable vaterite from transforming to calcite via a dissolution-recrystallization process. Further, the decrease of pH in the solution could reduce the chelation between Asp and Ca2+, leading to the transformation from vaterite to calcite. Hence, the study on the formation and transformation of vaterite will provide additional insight into biomineralization mechanism and industrial production. [ABSTRACT FROM AUTHOR]

Vaterite crystals with a spherical shape were successfully obtained by the addition of aspartic acid (Asp) in the calcium hydroxide (Ca(OH)2)-carbon dioxide reaction system. Crystalline products were characterized by X-ray diffraction, field emission scanning electron microscopy, Fourier transform infrared spectroscopy, Raman spectroscopy, thermogravimetric analysis, and differential scanning calorimetry (TG-DSC). The experimental results indicate that the addition of Asp can inhibit the growth of calcite but promote the formation of vaterite, and the spherical vaterite CaCO3 is gradually dominant along with the increase of Asp. Meanwhile the content of the vaterite phase is prominently influenced by the reaction temperature, and the optimal temperature for vaterite is at 40 °C. It is proposed that vaterite is induced through the intermediate chelated by Asp and Ca(OH)2, and then Asp is adsorbed on the surface of vaterite by chelation, preventing the metastable vaterite from transforming to calcite via a dissolution-recrystallization process. Further, the decrease of pH in the solution could reduce the chelation between Asp and Ca2+, leading to the transformation from vaterite to calcite. Hence, the study on the formation and transformation of vaterite will provide additional insight into biomineralization mechanism and industrial production. [ABSTRACT FROM AUTHOR]

Ethanol abuse affects virtually all organ systems and the central nervous system (CNS) is particularly vulnerable to excessive ethanol exposure. Ethanol exposure causes profound damages to both the adult and developing brain. Prenatal ethanol exposure induces fetal alcohol spectrum disorders (FASD) which is associated with mental retardation and other behavioral deficits. A number of potential mechanisms have been proposed for ethanol-induced brain damage; these include the promotion of neuroinflammation, interference with signaling by neurotrophic factors, induction of oxidative stress, modulation of retinoid acid signaling, and thiamine deficiency. The endoplasmic reticulum (ER) regulates posttranslational protein processing and transport. The accumulation of unfolded or misfolded proteins in the ER lumen triggers ER stress and induces unfolded protein response (UPR) which are mediated by three transmembrane ER signaling proteins: pancreatic endoplasmic reticulum kinase (PERK), inositol-requiring enzyme 1 (IRE1), and activating transcription factor 6 (ATF6). UPR is initiated to protect cells from overwhelming ER protein loading. However, sustained ER stress may result in cell death. ER stress has been implied in various CNS injuries, including brain ischemia, traumatic brain injury, and aging-associated neurodegeneration, such as Alzheimer's disease (AD), Huntington's disease (HD), Amyotrophic lateral sclerosis (ALS), and Parkinson's disease (PD). However, effects of ethanol on ER stress in the CNS receive less attention. In this review, we discuss recent progress in the study of ER stress in ethanol-induced neurotoxicity. We also examine the potential mechanisms underlying ethanol-mediated ER stress and the interaction among ER stress, oxidative stress and autophagy in the context of ethanol neurotoxicity. [ABSTRACT FROM AUTHOR]

We propose a simple method of realizing an accurate position detection of phase singularities in an optical vortex (OV) beam using a Shack-Hartmann wavefront sensor (SH-WFS). The method calculates circulations which are the discrete contour integrals of phase slope vectors measured by the SH-WFS and then determines the accurate positions of the singular points by calculating the centers-of-gravity with a fixed window size around the local peak of the circulation distribution. We use closed paths that connect the centers of eightconnected, instead of 2 x 2-neighboring lenslet apertures for calculating the circulations. Both the numerical analysis and proof-of-principle experiment were performed to confirm the measurement accuracy. In experiments, the positions of singular points in OV beams generated by a liquid-crystal-on-silicon spatial light modulator were measured. The root-mean-square error of the position measurement was approximately 0.09 in units of the lens size of the lenslet array used in the SH-WFS. We also estimated the topological charges of the singular points being detected based on the peak circulations, and the results agreed well with theoretical ones. The method achieves both rapid implementation and sublens-size spatial resolution detection and is suitable for applications that require real-time control of OV beams. [ABSTRACT FROM AUTHOR]

Understanding and predicting extreme weather and climate are ultimately important for adaptation and resilience. Here, we assess the prediction skills of frequency of summer extreme hot days (SEHDs) in the Asian monsoon region (AMR) by using the 1981-2014 hindcasts of the Predictive Ocean Atmosphere Model for Australia version 2 (POAMA-2) subseasonal-to-seasonal prediction system. Generally, the good prediction skills of SEHD frequency appear in the southern AMR south of 308N including the Indian subcontinent, Indo-China peninsula, and the Philippines; the anomaly correlation coefficients between the observed and predicted region-mean SEHD anomalies are 0.72, 0.72, 0.70, 0.60, 0.61, and 0.61 at 1-6 months lead, respectively, all statistically significant at the 99.9% confidence level. The high prediction skills in POAMA-2 are due to its capacity on reproducing the observed delayed ENSO impacts on the large-scale atmospheric circulation, the seasonal surface air temperature, and thus the SEHD frequency in the southern AMR via provoking the Indo--western Pacific Ocean capacitor effect. Since POAMA-2 only provides the prediction at most half a year in advance, we also conduct the hindcasts in the SINTEX-F that can reproduce well the robust ENSO--SEHD relationship and has high prediction skill of ENSO itself. Results show that skillful prediction of the region-mean SEHD frequency can be up to 14 months in advance. These results are complementary to Part I of this study that ENSO can impact the SEHDs in the AMR and provide the sources of predictability. [ABSTRACT FROM AUTHOR]

Background: Synaptic dysfunction is a key event in pathogenesis of neurodegenerative diseases such as Alzheimer's disease (AD) where synapse loss pathologically correlates with cognitive decline and dementia. Although evidence suggests that aberrant protein production and aggregation are the causative factors in familial subsets of such diseases, drugs singularly targeting these hallmark proteins, such as amyloid-β, have failed in late stage clinical trials. Therefore, to provide a successful disease-modifying compound and address synaptic dysfunction and memory loss in AD and mixed pathology dementia, we repurposed a clinically proven drug, CMZ, with neuroprotective and anti-inflammatory properties via addition of nitric oxide (NO) and cGMP signaling property.Results: The novel compound, NMZ, was shown to retain the GABAA potentiating actions of CMZ in vitro and sedative activity in vivo. Importantly, NMZ restored LTP in hippocampal slices from AD transgenic mice, whereas CMZ was without effect. NMZ reversed amnestic blockade of acetylcholine receptors by scopolamine as well as NMDA receptor blockade by a benzodiazepine and a NO synthase inhibitor in the step-through passive avoidance (STPA) test of learning and working memory. A PK/PD relationship was developed based on STPA analysis coupled with pharmacokinetic measures of drug levels in the brain: at 1 nM concentration in brain and plasma, NMZ was able to restore memory consolidation in mice.Conclusion: Our findings show that NMZ embodies a promising pharmacological approach targeting synaptic dysfunction and opens new avenues for neuroprotective intervention strategies in mixed pathology AD, neurodegeneration, and dementia. [ABSTRACT FROM AUTHOR]

The Liangshan pig is a traditional Chinese small-sized breed; it has a relatively long feeding period and low meat production ability but superior meat quality. This study utilized three non-linear growth models (Von Bertalanffy, Gompertz, and logistic) tofit the growth curve of Liangshan pigs from an unselected, random-bred pig population and estimate the pigs most suitable slaughter weight. The growth development data at 20 time points of 275 Liangshan pigs (from birth to 250 d) were collected. To analyze the relative gene expression related to development, seven slaughter weight phases (50, 58, 66, 74, 82, 90, and 98 kg) (20 pigs per phase) were examined. We found that the Liangshan pig growth curve fit the typical S-curve well and that their growth turning point was 193.4 days at a weight of 62.5 kg, according to the best fit Von Bertalanffy model based on the goodness of fit criteria. Furthermore, we estimated that the most suitable slaughter weight was 62.5 to 74.9 kg based on the growth curve and the relative expression levels of growth-related genes. [ABSTRACT FROM AUTHOR]

R4694 --> 869.5 --> Intraepithelial lymphocytes expressing the γδ T cell receptor (γδ IEL) are located within the intestinal epithelium and serve as the first line of defense against pathogen invasion. We recently identified a novel hyperproliferative and hypermotile γδ IEL (γδHYP) phenotype that can be transferred both horizontally and vertically to wildtype (WT) mice via the gut microbiota. Given the close relationship between metabolism and immune cell function, as well as the influence of commensals on T cell metabolism, we hypothesized that the bioenergetic potential of γδHYP IELs is increased to support this enhanced proliferation and motility. Transmission electron microscopy of sorted small intestinal γδ IELs revealed that γδHYP IELs exhibit a 70% increase in the number of mitochondria per cell (p=0.005) accompanied by a 24% increase in mitochondrial area (p=0.04) and 40% increase in aspect ratio (p=0.02) relative to WT. Since elongated mitochondria may be indicative of increased oxidative phosphorylation, we next performed Seahorse mitochondrial stress assays on sorted γδ IELs to assess the bioenergetic capacity of these lymphocytes. We find that γδHYP IELs exhibit a 50% increase in spare respiratory capacity compared to WT (p=0.014). Bulk RNA sequencing was performed on WT and γδHYP IELs and transcriptomic analysis revealed that γδHYP IELs upregulate genes involved in cell cycle (p<0.0001), as well as cholesterol and lipid metabolism (p<0.0001) compared to WT. Given the role of cholesterol and lipid metabolism in T cell activation and proliferation, we next analyzed intracellular cholesterol and lipid content within WT and γδHYP IELs using Filipin III and LipidTOX staining followed by flow cytometry. Interestingly, while there is a 3‐fold increase in neutral lipids in γδHYP IELs (p<0.0001), cholesterol content is equivalent between WT and γδHYP IELs. Glucose and mitochondrial metabolism, as well as neutral lipid content, was recently shown to influence cytokine production by γδ T cells. Upon stimulation with phorbol myristate acetate (PMA) and ionomycin, the frequency of IFNγ+ γδ IELs was reduced by 59% with a 44% decrease in IFNγ mean fluorescence intensity (MFI) in γδHYP IELs relative to WT (p<0.0001). Although IFNγ production is reduced in γδHYP IELs, transcriptomic analysis revealed an increase in genes associated with antimicrobial defense including Reg3g (p<0.0001). In support of this, we find that γδHYP mice exhibit reduced bacterial burden in the spleen and liver 6 days post‐infection with Salmonella Typhimurium compared to WT. In summary, our data demonstrate that the increased mitochondrial mass and oxidative phosphorylation observed in γδHYP IELs, in addition to increased neutral lipid accumulation, may contribute to this hyperproliferative and hypermotile phenotype and decreased IFNγ production. Further understanding of the metabolic mechanisms regulating γδ IEL homeostasis and effector function may ultimately allow fine tuning of mucosal surveillance to protect against intestinal injury or infection. [ABSTRACT FROM AUTHOR]

R3479 --> 867.6 --> Intraepithelial lymphocytes (IEL) expressing the γδ T cell receptor (TCR) constantly survey the intestinal epithelium, facilitating a localized effector response to limit pathogen invasion. Despite constant γδ TCR triggering in vivo, these IELs remain immunologically quiescent, suggesting that a co‐stimulatory signal is required to overcome their activation threshold. Type I interferon (IFN) is a family of pro‐inflammatory cytokines that are critical for host defense against bacterial and viral infection. Activated γδ IELs limit viral replication in intestinal epithelial cells by producing type I IFNs, such as IFNα; however, the role of IFNα in mediating γδ IEL antiviral effector function remains unknown. To determine whether IFNα directly activates these sentinel lymphocytes, murine small intestinal γδ IELs were isolated, sorted, and stimulated ex vivo with 1μg/mL αCD3, 10 ng/mL IFNα, or both for 5 h. Following treatment with αCD3 and IFNα, we observed a 27%±9.3 increase in IFNγ+ γδ IELs (p<0.0001) and a 2.5‐fold increase in IFNγ mean fluorescence intensity (MFI)(p<0.0001) compared to αCD3 stimulation. Interestingly, IFNα treatment alone was not sufficient to induce IFNγ production. To determine the threshold of TCR signaling necessary for this enhanced IFNγ production, we treated γδ IELs with suboptimal concentrations of αCD3 (0.01 or 0.1 μg/mL), to mimic constant TCR triggering in vitro.At 0.1 μg/mL αCD3, IFNα induced a 27%±7.2 increase in frequency of IFNγ+ γδ IELs (p<0.01) and a significant increase in MFI of γδ IEL IFNγ production over αCD3 treatment alone (p<0.001). With a low level of TCR priming (0.1 μg/mL αCD3), a low dose of IFNα (0.1 ng/mL) was able to stimulate a 22%±6.8 increase in IFNγ+ γδ IELs compared to αCD3 treatment alone. However, higher concentrations of IFNα failed to further enhance γδ IEL IFNγ production. Stimulation of γδ IELs with IFNα ex vivo was sufficient to induce STAT1 and STAT4 phosphorylation; therefore, we asked whether STAT1 or STAT4 is required for IFNα‐induced IFNγ production. To this end, we treated WT, STAT1 KO, or STAT4 KO γδ IELs with 1 μg/mL αCD3, 10 ng/mL IFNα, or both and found that the IFNα‐induced increase in IFNγ production was abrogated in STAT4‐, but not STAT1‐deficient γδ IELs (p<0.0001). To assess changes in STAT1 and STAT4 expression in γδ IELs during acute viral infection, WT mice were infected orally with 1.5x106 PFU murine gamma herpesvirus (MHV). We observed a 16%±3 increase in the frequency of γδ IELs 3 days post‐infection compared to controls, which corresponded with a decrease in total STAT1 (MFI: 905±95 vs 638±102, p<0.01). Taken together, our data demonstrate that γδTCR signaling is required for IFNα‐induced IFNγ production in a STAT4‐dependent manner. These findings suggest that IFNα signaling in conjunction with constant TCR triggering promotes the rapid activation and expansion of γδ IELs, which may enhance their effector response to microbial pathogens. [ABSTRACT FROM AUTHOR]

There is much evidence suggesting that CCL5 is one of the chemoattractant cytokines involved in diabetes mellitus (DM) with diffuse large B-cell lymphoma (DLBCL). However, the pathological impact is unclear. In the current study, in order to improve understanding regarding the role of CCL5 in DM with DLBCL, the expression levels of CCL5 mRNA were examined in normal B cells, human DLBCL cell lines (Ly1, Ly8 and Ly10) and a mouse DLBCL cell line (A20), as well as those in cells cultured with either 5 or 30 mmol/l glucose. A20-CCL5+ (CCL5 overexpression) and A20-CCL5- (CCL5 knockdown) subclones were obtained through cell transduction with a lentiviral vector, and were subcutaneously injected into BALB/c DM mice and normal mice. Tumor growth was observed by calculating the tumor volume. The results demonstrated that CCL5 mRNA levels in DLBCL cells were significantly higher than those in the normal cells (P<0.05); and levels in DLBCL cells in 30 mmol/l Glu were significantly higher than in those of DLBCL cells in 5 mmol/l Glu (P<0.05). A20-CCL5+ cells led to tumor formation in DM mice compared with A20 and A20-CCL5- cells. These results indicate that high levels of CCL5 expression may accelerate DLBCL formation in DM. [ABSTRACT FROM AUTHOR]

The synthesis and structural comparison are reported herein for a series of late first-row transition metal complexes using a macrocyclic pyridinophane ligand, NJJ'-diferf-butyl-2,ll-diaza[3.3](2,6)pyridinophane (tBuN4). The tBuN4 ligand enforces a distorted octahedral geometry in complexes [(tBuN4)MII(MeCN)2](OTf)2 (M = FeII, CoII, NiII, CuII), [(tBuN4)ZnII(MeCN)(OTf)](OTf), and [(tBuN4)- Fem(OMe)2] (OTf), with elongated axial M-Namine distances compared to the equatorial M--Npy distances. The geometry of [(tBuN4)CuI(MeCN)](OTf) is pentacoordinate with weak axial interactions with the amine N-donors of tBuN4. Complexes [(tBuN4)M(MeCN)2](OTf)2 (M = Fe, Co) exhibit magnetic properties that are intermediate between those expected for high spin and low spin complexes. Electrochemical studies of (tBuN4)M complexes suggest that tBuN4 is suitable to stabilize CoI, NiI, CoIII, FeIII solvato-complexes, while the electrochemical oxidation of (tBuN4)NiCl2 complex leads to formation of a NiIII species, supporting the ability of the, tBuN4 ligand to stabilize first row transition metal complexes in various oxidation states. Importandy, the [(tBuN4)MII(MeCN)2]2+ complexes exhibit two available cis coordination sites and thus can mediate reactions involving exogenous ligands. For example, the [(tBuN4)CuII(MeCN)2]2+ species acts as an efficient Lewis acid and promotes an uncommon hydrolytic coupling of nitriles. In addition, initial UV--vis and electron paramagnetic resonance (EPR) studies show that the [(tBuN4)FeII(MeCN)2]2+ complex reacts with oxidants such as H2O2 and peracetic acid to form high-valent Fe transient species. Overall, these results suggest that the (tBuN4MII systems should be able to promote redox transformations involving exogenous substrates. [ABSTRACT FROM AUTHOR]

Human and animals studies support the idea that there is a gender-related co-morbidity of pain-related and inflammatory gastrointestinal (GI) diseases with psychological disorders. This co-morbidity is the evidence for the existence of GI-brain axis which consists of immune (cytokines), neural (vagus nerve) and neuroendocrine (HPA axis) pathways. Psychological stress causes disturbances in GI physiology, such as altered GI barrier function, changes in motility and secretion, development of visceral hypersensitivity, and dysfunction of inflammatory responses. Whether GI inflammation would exert impact on psychological behavior is not well established. We examined the effect of experimental gastritis on anxiety- and depression-like behaviors in male and female Sprague-Dawley rats, and evaluated potential mechanisms of action. Gastritis was induced by adding 0.1% (w/v) iodoacetamide (IAA) to the sterile drinking water for 7 days. Sucrose preference test assessed the depression-like behavior, open field test and elevated plus maze evaluated the anxietylike behavior. IAA treatment induced gastric inflammation in rats of either gender. No behavioral abnormality or dysfunction of GI-brain axis was observed in male rats with IAAinduced gastritis. Anxiety- and depression-like behaviors were apparent and the HPA axis was hyperactive in female rats with IAA-induced gastritis. Our results show that gastric inflammation leads to anxiety- and depression-like behaviors in female but not male rats via the neuroendocrine (HPA axis) pathway, suggesting that the GI inflammation can impair normal brain function and induce changes in psychological behavior in a gender-related manner through the GI-to-brain signaling. [ABSTRACT FROM AUTHOR]

BACKGROUND AND OBJECTIVE Fractional photothermolysis (FP) lasers have been widely used in treating photo-aged skin, acne scars, and other skin conditions. Although plenty of clinical data have demonstrated the efficacy of the FP laser, only limited histologic studies have been available to observe serial short- to long-term skin responses. METHODS Seven healthy Chinese women received one pass of fractional carbon dioxide laser treatment on the left upper back. Biopsies were taken at the baseline and 4 hours, 1 day, 5 days, 1 month, 3 months, 6 months, and 1 year after the procedure for hematoxylin and eosin stains, immunohistochemical evaluation (for heat shock proteins and elastin), and Verhoeff-iron-hematoxylin stains (for collagen and elastic fiber). RESULTS Remarkably greater expression of heat shock protein (HSP)70 could be observed 4 hours after the procedure, which diminished significantly by 3 months, 6 months, and 1 year after the procedure. HSP47 reached its peak expression 1 month after the procedure, especially around microscopic thermal zones, and maintained its high level of expression 3 and 6 months after the procedure. Distinct new formation and remodeling of collagen and elastic fibers could be observed 3 and 6 months after procedure. CONCLUSION FP-induced HSP expression and new formation of collagen and elastic fibers lasted as long as 6 months, longer than the previously acknowledged 3 months. The authors have indicated no significant interest with commercial supporters. [ABSTRACT FROM AUTHOR]

The tridentate ligand N-methyl-N,N-bis(2-pyridylmethyl)amine (L) has been employed to synthesize a dinuclear Co(II)Co(III) mixed-valence complex containing μ-methoxo and μ-carboxylato bridging ligands, [LCoII(μ-carboxylato)bis(μ-methoxo)CoIIIL](ClO4)2. In this complex, the two pseudo-octahedral Co centers have an identical ligand environment, yet the average Co-N and Co-O bond distances at the two Co ions differ significantly. Electrochemical, spectroscopic, and magnetic susceptibility measurements confirm that it belongs to a localized Class II mixed-valence system, despite the presence of a short Co…Co distance of 3.021 Å. Oxidation of this Co(II)Co(III) complex leads to formation of the corresponding Co(III)Co(III) complex that was characterized structurally and spectroscopically. In addition, dinuclear and trinuclear μ-hydroxo Co(III) complexes have been obtained in the presence of phosphate anions and absence of methanol, respectively, suggesting that an additional bridging ligand is needed to stabilize the CoIIIbis(μ-hydroxo)CoIII fragment. Moreover, the ability of the mixed-valence Co(II)Co(III) complex and the three related Co(III) complexes to electrocatalytically oxidize water was also investigated. The observed limited water oxidation catalytic ability for these systems suggests that a multinuclear Co cluster and/or presence of O-rich ligands may be needed for the generation of efficient molecular Co-based water oxidation catalysts. [ABSTRACT FROM AUTHOR]

Surface air temperature (SAT) over the globe, particularly the Northern Hemisphere continents, has rapidly risen over the last 2--3 decades, leading to an abrupt shift toward a warmer climate state after 1997/98. Whether the terrestrial warming might be caused by local response to increasing greenhouse gas (GHG) concentrations or by sea surface temperature (SST) rise is recently in dispute. The SST warming itself may be driven by both the increasing GHG forcing and slowly varying natural processes. Besides, whether the recent global warming might affect seasonal-to-interannual climate predictability is an important issue to be explored. Based on the Japan Agency for Marine-Earth Science and Technology (JAMSTEC) climate prediction system in which only observed SSTs are assimilated for coupled model initialization, the present study shows that the historical SST rise plays a key role in driving the intensified terrestrial warming over the globe. The SST warming trend, while negligible for short lead predictions, has substantial impact on the climate predictability at long lead times (>1 yr) particularly in the extratropics. The tropical climate predictability, however, is little influenced by global warming. Given a perfect warming trend and/or a perfect model, global SAT and precipitation could be predicted beyond two years in advance with an anomaly correlation skill above ∼∼0.6. Without assimilating ocean subsurface observations, model initial conditions show a strong spurious cooling drift of subsurface temperature; this is caused by large negative surface heat flux damping arising from the SST-nudging initialization. The spurious subsurface cooling drift acts to weaken the initial SST warming trend during model forecasts, leading to even negative trends of global SAT and precipitation at long lead times and hence deteriorating the global climate predictability. Concerning the important influence of the subsurface temperature on the global SAT trend, future efforts are required to develop a good scheme for assimilating subsurface information particularly in the extratropical oceans. [ABSTRACT FROM AUTHOR]

Cotton verticillium wilt ( Verticillium dabliae Kleb.) is a very destructive disease. In this study, we evaluated a Bacillus subtilis enhanced bio-organic fertilizer (BOF) for control of the disease and for its effect on rhizosphere microbiota. Greenhouse pot experiments were conducted during three cotton (Gossypium hirsutum L.) growing seasons with serial treatments of BOF or unenhanced organic fertilizer (OF). Consistent control of cotton verticillium wilt was obtained in the three trials. The complete BOF treatment, in which both nursery cups with healthy soils and transplanted pots with diseased soils were amended with BOF, was the most effective in reducing the counts of pathogenic V. dabliae and of total fungi in the cotton rhizosphere. The complete BOF treatment was also the most effective in reducing disease incidence. Rhizosphere soil DNA was extracted at harvest and the 5' end (370 base pairs) of the fungal 18S rRNA gene was amplified by using the primer pair NS1 and GCFung (fungus specific). Seventy-one bands were recognized in denaturing gradient gel electrophoresis (DGGE) gels and excised for sequencing, but only 35 bands were successfully sequenced during the study. Nonmetric multidimensional sealing analysis of DGGE patterns showed that the complete BOF treatments were not close to any other treatment. Ribotypes related to four Ascomycota and two Basidiomycota fungi were detected in the untreated but not in the BOF-amended soil. The results suggest that the complete BOF treatment could effectively control cotton verticillium wilt by significantly improving fungal structure in rhizosphere soils. [ABSTRACT FROM AUTHOR]

Inhibitors of histone deacetylases, including suberoylanilide hydroxamic acid (SAHA) and trichostatin A (TSA), are emerging anticancer agents. In the current study, we examined the cytoprotective effects of these agents. Cisplatin induced 40-50% apoptosis in rat kidney proximal tubular cells in 18 h, which was suppressed to 20-30% by 1-5 μM SAHA or 0.1 μM TSA. Consistently, SAHA partially prevented cisplatin-induced caspase activation. The cytoprotective effects of SAHA and TSA were associated with long-term cell survival. During cisplatin treatment, Bax translocated to mitochondria, leading to cytochrome c release. Both Bax translocation and cytochrome c release were ameliorated by SAHA. Mechanistically, SAHA inhibited and TSA delayed p53 phosphorylation, acetylation, and activation during cisplatin incubation. At the upstream signaling level, SAHA blocked cisplatin-induced phosphorylation of Chk2, a key DNA damage response kinase. Interestingly, in HCT116 colon cancer cells, SAHA suppressed cisplatin-induced p13 activation, but enhanced apoptosis. The results suggest that inhibitors of histone deacetylases can protect against cisplatin nephrotoxicity by attenuating DNA damage response and associated p53 activation. [ABSTRACT FROM AUTHOR]

Heavy alcohol exposure produces profound damage to the developing central nervous system (CNS) as well as the adult brain. Children with fetal alcohol spectrum disorders (FASD) have a variety of cognitive, behavioral, and neurological impairments. FASD currently represents the leading cause of mental retardation. Excessive alcohol consumption is associated with Wernicke–Korsakoff syndrome (WKS) and neurodegeneration in the adult brain. Although the cellular/molecular mechanism underlying ethanol’s neurotoxicity has not been fully understood, it is generally believed that oxidative stress plays an important role. Identification of neuroprotective agents that can ameliorate ethanol neurotoxicity is an important step for developing preventive/therapeutic strategies. Targeting ethanol-induced oxidative stress using natural antioxidants is an attractive approach. Anthocyanins, a large subgroup of flavonoids present in many vegetables and fruits, are safe and potent antioxidants. They exhibit diverse potential health benefits including cardioprotection, anti-atherosclerotic activity, anti-cancer, anti-diabetic, and anti-inflammation properties. Anthocyanins can cross the blood–brain barrier and distribute in the CNS. Recent studies indicate that anthocyanins represent novel neuroprotective agents and may be beneficial in ameliorating ethanol neurotoxicity. In this review, we discuss the evidence and potential of anthocyanins in alleviating ethanol-induced damage to the CNS. Furthermore, we discuss possible underlying mechanisms as well as future research approaches necessary to establish the therapeutic role of anthocyanins. [ABSTRACT FROM AUTHOR]

Evolution of Indian Ocean Dipole (IOD) events in 2003, 2006 and 2007 is investigated using observational and re-analysis data products. Efforts are made to understand various processes involved in three phases of IOD events; activation, maturation and termination. Three different triggers are found to activate the IOD events. In preceding months leading to the IOD evolution, the thermocline in southeastern Indian Ocean shoals by reflection of near equatorial upwelling Rossby waves at the East African coast into anomalous upwelling equatorial Kelvin waves. Strengthening (weakening) of northern (southern) portion of ITCZ in March/April and May/June of IOD years, leads to strengthening of alongshore winds along Sumatra/Java coasts. With the combined shallow thermocline and increased latent heat flux due to enhanced wind speeds, the SST in the southeastern Indian Ocean cools in following months. On intraseasonal time scales convection-suppressing phase of Madden-Julian oscillation (MJO) propagates from west to east in May/June of IOD year, and easterlies associated with this phase of MJO causes further shoaling of thermocline in southeastern Indian Ocean, through anomalous upwelling Kelvin wave. All these three mechanisms appear to be involved in initiating IOD event in 2006. On the other hand, except the strengthening/weakening of ITCZ, all other mechanisms are involved in activation of 2003 IOD event. Activation of 2007 IOD event was due to propagation of convection-suppressing MJO in May/June and strengthening of mean winds along Sumatra/Java coast from March to June through changes in convection. The IOD events matured into full-fledged events in the following months after activation, by surface heat fluxes, vertical and horizontal advection of cool waters supported by local along-shore upwelling favorable winds and remote equatorial easterly wind anomalies through excitation of upwelling Kelvin waves. Propagating MJO signals in the tropical Indian Ocean brings significant changes in evolution of IOD events on MJO time scales. Termination of 2003 and 2007 IOD events is achieved by strong convection-enhancing MJOs propagating from west to east in the tropical Indian Ocean which deepen the thermocline in the southeastern equatorial Indian Ocean. IOD event in 2006 was terminated by seasonal reversal of monsoon winds along Sumatra/Java coasts which stops the local coastal upwelling. [ABSTRACT FROM AUTHOR]

The non-steroidal anti-inflammatory drug flurbiprofen is a selective amyloid lowering agent which has been studied clinically in Alzheimer’s disease. HCT-1026 is an ester prodrug of flurbiprofen incorporating a nitrate carrier moiety that in vivo provides NO bioactivity and an improved safety profile. In vitro, HCT-1026 retained the cyclooxygenase inhibitory and non-steroidal anti-inflammatory drug activity of flurbiprofen, but at concentrations at which levels of amyloid-β 1–42 amino acid were lowered by flurbiprofen, amyloid-β 1–42 amino acid levels were elevated 200% by HCT-1026. Conversely, at lower concentrations, HCT-1026 behaved as a selective amyloid lowering agent with greater potency than flurbiprofen. The difference in concentration–responses between flurbiprofen and HCT-1026 in vitro suggests different cellular targets; and in no case did a combination of nitrate drug with flurbiprofen provide similar actions. In vivo, HCT-1026 was observed to reverse cognitive deficits induced by scopolamine in two behavioral assays; activity that was also shown by a classical nitrate drug, but not by flurbiprofen. The ability to restore aversive memory and spatial working and reference memory after cholinergic blockade has been demonstrated by other agents that stimulate NO/cGMP signaling. These observations add positively to the preclinical profile of HCT-1026 and NO chimeras in Alzheimer’s disease. [ABSTRACT FROM AUTHOR]

The synthesis of 1,2-naphtho-annelated barrelene derivatives, namely dimethyl-7,12-dihydro-7,12-ethenobenzo[a]anthracene-13,14-dicarboxylate (4a) and dimethyl-7,14-dihydro-7,14-ethenodibenzo[a,j]-anthracene-15,16-dicarboxylate (4b), and the investigation of their photoreactivity in solution and in the solid state is reported. The irradiation of 4a and 4b resulted in regioselective di-π-methane rearrangements to give semibullvalene products; however, the product distribution is inverted upon changing the reaction medium from solution to the solid state. In solution, an α-naphtho–vinyl bridging predominates as the initial photochemical step because of the selective stabilization of the corresponding transition state, as discussed on the basis of the structures of the related biradical intermediates, whereas the solid-state photoreaction is significantly influenced by the steric constraints within the crystal lattice that only allow a β-naphtho–vinyl bridging. On a réalisé la synthèse de dérivés condensés 1,2-naphtobarrèlènes, à savoir le 7,12-dihydro-7,12-éthénobenzo[a]anthracène-13,14-dicarboxylate de diméthyle (4a) et le 7,14-dihydro-7,14-éthénobenzo[a,j]anthracène-15,16-dicarboxylate de diméthyle (4b), et on a étudié leur photoréactivité en solution et à l’état solide. L’irradiation des composés 4a et 4b conduit à des réarrangements di-π-méthane régiosélectifs et à la formation de produits semibullvalènes; toutefois, la distribution des produits est inversée lorsque le milieu réactionnel passe de la solution à l’état solide. En solution, un pont α-naphtovinyle prédomine comme étape photochimique initiale en raison de la stabilisation sélective de l’état de transition correspondant, tel que discuté sur la base des structures des intermédiaires biradicalaires apparentés, alors que la photoréaction à l’état solide est fortement influencée par des contraintes stériques dans le réseau cristallin qui ne permettent que la formation d’un pont β-naphtovinyle. [ABSTRACT FROM AUTHOR]

Previously we reported that priming of visual motion perception is reduced in older adults compared to younger adults (Jiang, Greenwood, & Parasuraman, 1999, Psychology and Aging, 14(4), 619; Jiang, Luo, & Parasuraman, 2002b, Neuropsychology, 16(2), 140). To examine the neural mechanisms underlying this age-related effect, event-related brain potentials (ERPs) were recorded during perceptual judgments of motion directions by younger and older adults in two experiments. When judging single-step motion, both younger and older adults evoked significantly larger ERP late positive component (LPC) responses to unambiguous motion compared to LPC responses elicited by ambiguous motion. In contrast, compared to the younger adults, the older adults evoked comparable but delayed ERP responses to single motion steps. In the second experiment the younger and older groups judged the directions of two successive motion-steps (either motion priming or motion reversals). Under short (200-400 ms) stimulus onset asynchrony (SOA), the difference between the ERP responses to priming and reversal conditions was significantly larger for the younger than for the older adults. This study provides the first electrophysiological evidence that brain aging leads to delayed processing of single motion direction and visual motion priming as early as 100 ms in the early visual cortex. Age-related changes in strength and temporal characteristics of neural responses in temporal-parietal regions were particularly pronounced in older adults when successive motion signals are placed closely in time, within 400 ms. [ABSTRACT FROM AUTHOR]

The tropical Indian Ocean climate variability is investigated using an artificial neural network analysis called self-organizing map (SOM) for both observational data and coupled model outputs. The SOM successfully captures the dipole sea surface temperature anomaly (SSTA) pattern associated with the Indian Ocean Dipole (IOD) and basin-wide warming/cooling associated with ENSO. The dipole SSTA pattern appears only in boreal summer and fall, whereas the basin-wide warming/cooling appears mostly in boreal winter and spring owing to the phase-locking nature of these phenomena. Their occurrence also undergoes significant decadal variation. Composite diagrams constructed for nodes in the SOM array based on the simulated SSTA reveal interesting features. For the nodes with the basin-wide warming, a strong positive SSTA in the eastern equatorial Pacific, a negative Southern Oscillation, and a negative precipitation anomaly in East Africa are found. The nodes with the positive IOD are associated with a weak positive SSTA in the central equatorial Pacific or positive SSTA in the eastern equatorial Pacific, a positive (negative) sea level pressure anomaly in the eastern (western) tropical Indian Ocean, and a positive precipitation anomaly over East Africa. The warming in the central equatorial Pacific appears to correspond to El Niño Modoki discussed recently. These results suggest usefulness of SOM in studying large-scale ocean–atmosphere coupled phenomena. [ABSTRACT FROM AUTHOR]

Using a fully coupled global ocean–atmosphere general circulation model assimilating only sea surface temperature, the authors found for the first time that several El Niño–Southern Oscillation (ENSO) events over the past two decades can be predicted at lead times of up to 2 yr. The El Niño condition in the 1997/98 winter can be predicted to some extent up to about a 1½-yr lead but with a weak intensity and large phase delay in the prediction of the onset of this exceptionally strong event. This is attributed to the influence of active and intensive stochastic westerly wind bursts during late 1996 to mid-1997, which are generally unpredictable at seasonal time scales. The cold signals in the 1984/85 and 1999/2000 winters during the peak phases of the past two long-lasting La Niña events are predicted well up to a 2-yr lead. Amazingly, the mild El Niño–like event of 2002/03 is also predicted well up to a 2-yr lead, suggesting a link between the prolonged El Niño and the tropical Pacific decadal variability. Seasonal climate anomalies over vast parts of the globe during specific ENSO years are also realistically predicted up to a 2-yr lead for the first time. [ABSTRACT FROM AUTHOR]

Using outputs from the SINTEX-F1 coupled GCM, the thermodynamics of ENSO events and its relation with the seasonal cycle are investigated. Simulated El Niño events are first classified into four groups depending on during which season the Niño-3.4 sea surface temperature anomaly (SSTA) index (5°S–5°N, 120°–170°W) reaches its peak. Although the heat content of the tropical Pacific decreases for all four types, the tropical Pacific loses about twice as much during an El Niño that peaks during winter compared with one that peaks during summer. The surface heat flux, the southward heat transport at 15°S, and the Indonesian Throughflow heat transport contribute constructively to this remarkable seasonal difference. It is shown that the Indonesian Throughflow supplies anomalous heat from the Indian Ocean, especially during the summer El Niño–like event. Changes in the basic state provided by the seasonal cycle cause differences in the atmospheric response to the SSTA, which in turn lead to the difference between the surface heat flux and the meridional heat transport anomaly. [ABSTRACT FROM AUTHOR]

The decadal variation in the tropical Indian Ocean is investigated using outputs from a 200-yr integration of the Scale Interaction Experiment-Frontier Research Center for Global Change (SINTEX-F1) ocean–atmosphere coupled model. The first EOF mode of the decadal bandpass- (9–35 yr) filtered sea surface temperature anomaly (SSTA) represents a basinwide mode and is closely related with the Pacific ENSO-like decadal variability. The second EOF mode shows a clear east–west SSTA dipole pattern similar to that of the interannual Indian Ocean dipole (IOD) and may be termed the decadal IOD. However, it is demonstrated that the decadal air–sea interaction in the Tropics can be a statistical artifact; it should be interpreted more correctly as decadal modulation of interannual IOD events (i.e., asymmetric or skewed occurrence of positive and negative events). Heat budget analysis has revealed that the occurrence of IOD events is governed by variations in the southward Ekman heat transport across 15°S and variations in the Indonesian Throughflow associated with the ENSO. The variations in the southward Ekman heat transport are related to the Mascarene high activities. [ABSTRACT FROM AUTHOR]

The Indian Ocean Dipole (IOD) has profound socioeconomic impacts on not only the countries surrounding the Indian Ocean but also various parts of the world. A forecast system is developed based on a relatively high-resolution coupled ocean–atmosphere GCM with only sea surface temperature (SST) information assimilated. Retrospective ensemble forecasts of the IOD index for the past two decades show skillful scores with up to a 3–4-month lead and a winter prediction barrier associated with its intrinsic strong seasonal phase locking. Prediction skills of the SST anomalies in both the eastern and western Indian Ocean are higher than those of the IOD index; this is because of the influences of ENSO, which is highly predictable. The model predicts the extreme positive IOD event in 1994 at a 2–3-season lead. The strong 1997 cold signal in the eastern pole, however, is not well predicted owing to errors in model initial subsurface conditions. The real-time forecast system with more ensembles successfully predicted the weak negative IOD event in the 2005 boreal fall and La Niña condition in the 2005/06 winter. Recent experimental real-time forecasts showed that a positive IOD event would appear in the 2006 summer and fall accompanied by a possible weak El Niño condition in the equatorial Pacific. [ABSTRACT FROM AUTHOR]

The morphogenesis of the cerebellar cortex depends on intrinsic genetic programs as well as orchestrated cell‐cell/cell‐extracellular matrix (ECM) interactions. The matrix metalloproteinase (MMP) family comprises of more than 20 members that catalyze the degradation of all the protein constituents of the ECM. These proteolytic endopeptidases mediate cell‐cell/cell‐ECM interactions by remodeling the ECM and modulating the activity of membrane‐associated receptors. The activity of MMPs is negatively controlled by the tissue inhibitors of metalloproteinases (TIMPs). The MMPs and TIMPs regulate diverse neuronal functions including migration, process extension and synaptic plasticity. MMP‐2, ‐3, ‐9, membrane type 5‐MMP (MT5‐MMP), TIMP‐1, ‐2 and ‐3 are expressed in the developing cerebellum. The spatiotemporal pattern of expression/activity of these enzymes suggests that they play a role in the development of the cerebellar cortex. Blockage of MMP‐2/‐9 activity by specific inhibitors or blocking antibody, as well as using MMP‐9 knock‐out mice, clearly establishes that MMP‐2/‐9 participates in the regulation of morphogenesis of the cerebellum. The potential contributions of these enzymes to granule neuron migration, Purkinje cell dendritogenesis and synaptogenesis are discussed. [ABSTRACT FROM AUTHOR]