We have recently reported that tetrahedral metallocene complexes containing vanadium(IV) (vanadocene) have potent spermicidal activity against human sperm. The spermicidal activity was dependent on vanadium(IV) as the central metal ion within the bis-cyclopentadienyl (Cp2)-metal complex, but the variation of diacido groups and/or replacement with bidentate ligands coordinated to the Cp2-vanadium(IV) moiety also significantly modulated the spermicidal potency. To assess the structure-activity relationship between vanadocenes and other coordination complexes of vanadium(IV), a set of 11 oxovanadium(IV) complexes with different geometrical configurations were synthesized and evaluated for spermicidal activity by computer-assisted sperm analysis. These complexes included mono and bis ancillary ligands, 1,10-phenanthroline (phen): [VO(phen), VO(phen)2, VO(Me2-phen), VO(Me2-phen)2, VO(Cl-phen), and VO(Cl-phen)2]; 2,2'-bipyridyl (bipy): [VO(bipy), VO(bipy)2, VO(Me2-bipy), and VO(Me2-bipy)2], linked via nitrogen atoms; and 5'-bromo-2'-hydroxyacetophenone (acph): [VO(Br,OH-acph)2], linked via oxygen donor atoms. All 11 oxovanadium(IV) complexes elicited concentration-dependent spermicidal activity at micromolar concentrations (EC50 values: 5.5-118 microM). The bis-phenanthroline complex of oxovanadium(IV), VO(Cl-phen)2, was the most active, and the mono bipyridyl complex, VO(bipy), was the least active; the order of efficacy was VO(Cl-phen)2>> VO(phen)2>> VO(Br,OH-acph)2>> VO(Me2-phen)>> VO(bipy)2>> VO(phen)>> VO(Cl-phen)>> VO(Me2-phen)2>> VO(Me2-bipy)2>> VO(Me2-bipy)>> VO(bipy). The neutral complex, VO(Br, OH-acph)2, induced rapid sperm immobilization (T1/2 = 38 sec). The sperm-immobilizing activity of mono- and bis-ligated oxovanadium(IV) complexes was irreversible, since the treated sperm underwent apoptosis, as determined by the flow cytometric quantitation of mitochondrial membrane potential, surface Annexin V binding assay, and in situ DNA nick-end labeling of sperm nuclei. The percentages of apoptotic sperm quantitated by the flow cytometric assay correlated well with the spermicidal potency of oxovanadium(IV) complexes. These results provide unprecedented evidence that the spermicidal and apoptosis-inducing activities of vanadium(IV) complexes are determined by the oxidation state of vanadium as well as their geometry. Because of its rapid and potent sperm-immobilizing activity, the bromo-hydroxyacetophenone complex, [VO(Br,OH-acph)2], may be useful as a contraceptive agent.

The etiological agent of Chagas disease, Trypanosoma cruzi, is an obligate intracellular parasite that infects an estimated 7 million people in the Americas, with an at-risk population of 70 million. Despite its recognition as the highest impact parasitic infection of the Americas, Chagas disease continues to receive insufficient attention and resources in order to be effectively combatted. Unlike the other parasitic trypanosomatids that infect humans (Trypanosoma brucei and Leishmania spp.), T. cruzi retains an ancestral mode of phagotrophic feeding via an endocytic organelle known as the cytostome-cytopharynx complex (SPC). How this tubular invagination of the plasma membrane functions to bring in nutrients is poorly understood at a mechanistic level, partially due to a lack of knowledge of the protein machinery specifically targeted to this structure. Using a combination of CRISPR/Cas9 mediated endogenous tagging, fluorescently labeled overexpression constructs and endocytic assays, we have identified the first known SPC targeted protein (CP1). The CP1 labeled structure co-localizes with endocytosed protein and undergoes disassembly in infectious forms and reconstitution in replicative forms. Additionally, through the use of immunoprecipitation and mass spectrometry techniques, we have identified two additional CP1-associated proteins (CP2 and CP3) that also target to this endocytic organelle. Our localization studies using fluorescently tagged proteins and surface lectin staining have also allowed us, for the first time, to specifically define the location of the intriguing pre-oral ridge (POR) surface prominence at the SPC entrance through the use of super-resolution light microscopy. This work is a first glimpse into the proteome of the SPC and provides the tools for further characterization of this enigmatic endocytic organelle. A better understanding of how this deadly pathogen acquires nutrients from its host will potentially direct us toward new therapeutic targets to combat infection.

A zirconocene double act: The course of zirconocene-mediated macrocyclization is controlled by templating effects. In macrocyclizations of bipyridine-containing diynes, the zirconocene reagent [Cp2 Zr(py)(Me3 SiC≡SiMe3 )] (1; py=pyridine) acts as both coupling and templating agent. Thus, by controlling the stoichiometry, dimeric or trimeric macrocycles are obtained.

Nitrogenase activity for Clostridium pasteurianum (Cp) at a Cp2:Cp1 ratio of 1.0 and Azotobacter vinelandii (Av) at Av2:Av1 protein ratios (R) of 1, 4 and 10 is determined as a function of increasing MoFe protein concentration from 0.01 to 5 microM. The rates of ethylene and hydrogen evolution for these ratios and concentrations were measured to determine the effect of extreme dilution on nitrogenase activity. The experimental results show three distinct types of kinetic behavior: (1) a finite intercept along the concentration axis (approximately 0.05 microM MoFe); (2) a non-linear increase in the rate of product formation with increasing protein concentration (approximately 0.2 microM MoFe) and (3) a limiting linear rate of product formation at high protein concentrations (>0.4 microM MoFe). The data are fitted using the following rate equation derived from a mechanism for which two Fe proteins interact cooperatively with a single half of the MoFe protein. (see equation) The equation predicts that the cubic dependence in MoFe protein gives rise to the non-linear rate of product formation (the dilution effect) at very low MoFe protein concentrations. The equation also predicts that the rate will vary linearly at high MoFe protein concentrations with increasing MoFe protein concentration. That these limiting predictions are in accord with the experimental results suggests that either two Fe proteins interact cooperatively with a single half of the MoFe protein, or that the rate constants in the Thorneley and Lowe model are more dependent upon the redox state of MoFe protein than previously suspected [R.N. Thornley and D. J. Lowe, Biochem. J. 224 (1984) 887-894]. Previous Klebsiella pneumoniae and Azotobacter chroococcum dilution results were reanalyzed using the above equation. Results from all of these nitrogenases are consistent and suggest that cooperativity is a fundamental kinetic aspect of nitrogenase catalysis.

Ceruloplasmin (Cp) was isolated from the sera of albino rats fed with silver nitrate (60 mg/kg of body weight). The oxidase activity of the enzyme was sharply decreased, while its concentration in the blood (as assayed immunologically) was slightly lower than in controls. The drop in the oxidase activity was caused by the replacement of several coppers by silver ions in the Cp molecule. Ag-Cp contained about four silver atoms per 1 mole of protein, its spectrum lacking maxima at 450 and 610 nm that are typical of normal Cp. When subjected to PAAG electrophoresis, Ag-Cp displayed two bands, one of which (Ag-Cp2) had the anodic mobility of normal Cp. The other band (Ag-CpI) migrated at a slower rate. Both bands were separately subjected to SDS-PAAG electrophoresis which revealed the dissimilarities among the proteolytic fragment patterns of Ag-CpI, Ag-Cp2 and normal Cp. Both Ag-CpI and Ag-Cp2 contained peculiar fragments produced by spontaneous limited proteolysis of the native molecule. The binding of silver ions by Cp seems to alter significantly the molecule conformation, which may cause the exposure of new peptide bonds susceptible to proteolytic attack. Cp seems to participate in the binding and detoxication of heavy metals in mammals.

The aim of this study was to compare the performance of serological versus molecular typing methods to detect capsular polysaccharide (CP) and surface-associated polysaccharide antigen 336 phenotypes of Staphylococcus aureus isolates. Molecular typing of CP types 1, 5 and 8 was carried out using PCR, whereas serological typing of CP1, 2, 5, 8 and antigen 336 was carried out by slide agglutination using specific antisera. By genotyping, 14/31 strains were CP8 positive, 12/31 strains were CP5 and the remaining 6/31 isolates were non-typable (NT). One isolate was positive for both CP5 and CP8 by PCR, but was confirmed as CP8 type serologically. Detection of CP2 and type 336 by PCR was not possible because specific primers were either not available or non-specific. Using serotyping, 14/31 strains were CP8 positive, 11/31 CP5 positive and 2/31 positive for antigen 336. The remaining four S. aureus isolates were serologically NT. However, three of four NT and two 336-positive S. aureus isolates were encapsulated as determined by light microscopy after capsular staining. This discovery was surprising and warrants further investigations on the identification and characterization of additional capsular phenotypes prevalent among S. aureus clinical isolates. It was concluded that serological typing was a better method than molecular typing for use in epidemiological investigations based upon the distribution of surface-associated polysaccharide antigens-based phenotypes.

A new class of luminescent Ir^III antitumor agents, namely, [Ir(CP1)(PY1)₂] (Ir-1), [Ir(CP1)(PY2)₂] (Ir-2), [Ir(CP1)(PY4)₂] (Ir-3), [Ir(CP2)(PY1)₂] (Ir-4), [Ir(CP2)(PY4)₂] (Ir-5), [Ir(CP3)(PY1)₂]⋅CH₃OH (Ir-6), [Ir(CP4)(PY4)₂]⋅CH₃OH (Ir-7), [Ir(CP5)(PY2)₂] (Ir-8), [Ir(CP5)(PY4)₂]⋅CH₃OH (Ir-9), [Ir(CP6)(PY1)₂] (Ir-10), [Ir(CP6)(PY2)₂]⋅CH₃OH (Ir-11), [Ir(CP6)(PY3)₂] (Ir-12), [Ir(CP6)(PY41)₂] (Ir-13), and [Ir(CP7)(PY1)₂] (Ir-14), supported by 8-oxychinolin derivatives and 1-phenylpyrazole ligands was prepared. Compared with SK-OV-3/DDP and HL-7702 cells, the Ir-1-Ir-14 compounds exhibited half maximal inhibitory concentration (IC₅₀) values within the high nanomolar range (50 nM-10.99 μM) in HeLa cells. In addition, Ir-1 and Ir-3 accumulated and stained the mitochondrial inner membrane of HeLa cells with high selectivity and exhibited a high antineoplastic activity in the entire cervical HeLa cells, with IC₅₀ values of 1.22 ± 0.36 μM and 0.05 ± 0.04 μM, respectively. This phenomenon induced mitochondrial dysfunction, suggesting that these cyclometalated Ir^III complexes can be potentially used in biomedical imaging and Ir(III)-based anticancer drugs. Furthermore, the high cytotoxicity activity of Ir-3 is correlated with the 1-phenylpyrazole (H-PY4) secondary ligands in the luminescent Ir^III antitumor complex.

Bismetallocenes [Cp2 LuReCp2 ] and [Cp*2 LaReCp2 ] (Cp=cyclopentadienyl; Cp*=pentamethylcyclopentadienyl) were prepared using different synthetic strategies. Salt metathesis-performed in aromatic hydrocarbons to avoid degradation pathways caused by THF-were identified as an attractive alternative to alkane elimination. Although alkane elimination is more attractive in the sense of its less elaborate workup, the rate of the reaction shows a strong dependence on the ionic radius of Ln(3+) (Ln=lanthanide) within a given ligand set. Steric hindrance can cause a dramatic decrease in the reaction rate of alkane elimination. In this case, salt metathesis should be considered the better alternative. Covalent bonding interactions between the Ln and transition-metal (TM) cations has been quantified on the basis of the delocalization index. Its magnitude lies within the range characteristic for bonds between transition metals. Secondary interactions were identified between carbon atoms of the Cp ligand of the transition metal and the Ln cation. Model calculations clearly indicated that the size of these interactions depends on the capability of the TM atom to act as an electron donor (i.e., a Lewis base). The consequences can even be derived from structural details. The observed clear dependency of the LuRu and interfragment LuC bonding on the THF coordination of the Lu atom points to a tunable Lewis acidity at the Ln site, which provides a method of significantly influencing the structure and the interfragment bonding.

Coat protein genes CP1, CP2 and CP3 of an isolate (MaP1) of rice tungro spherical virus (RTSV) from Malaysia were isolated, cloned and sequenced. Comparative analysis indicated that MaP1 isolate is closely related to the Philippine isolate.

Isostructural Zn(II)/Cd(II) mixed ligand coordination polymers (CPs) {[M(IPA)(L)]}n (CP1 and CP2) built from isophthalic acid (H2IPA) and 3-pyridylcarboxaldehyde nicotinoylhydrazone (L) were prepared using versatile synthetic routes: viz., diffusion of precursor solutions, conventional reflux methods, and green mechanochemical (grinding) reactions. Both robust CPs synthesized by different routes were characterized by various analytical methods, and their thermal and chemical stability as well as the phase purity was established. Crystallographic studies revealed that CP1 and CP2 are isostructural frameworks and feature a double-lined two-dimensional network composed of Zn2+/Cd2+ nodes connected through IPA and pillared by the Schiff base ligand L with a double-walled edge. The photoluminescent (PL) properties of CP1 and CP2 have been exploited as dual detection fluorosensors for hexavalent chromate anions (CrO42-/Cr2O72-) and 2,4,6-trinitrophenol (TNP) because it was observed that the emission intensity of aqueous suspensions of CPs selectively quenches by chromate anions or TNP among large pools of different anions or nitro compounds, respectively. Competitive experiments in the presence of interfering anions/other nitro compounds also revealed no major effect in the quenching efficiency, suggesting the selective detection of hexavalent chromate anions as well as TNP by the LCPs. The limits of detection by CP1 for CrO42-/Cr2O72- and TNP are 4 ppm/4 ppm and 28 ppb, respectively, whereas the limits of detection by CP2 for the same analytes are 1 ppm/1 ppm and 14 ppb, respectively. A probable mechanism for the quenching phenomena is also discussed.

D5d- and C5v-symmetric double-decker buckyferrocene Fe2(C60R10)Cp2 (R10 = Me5Ph5 and Me10) represents a new type of diiron complexes featuring conjugative connection of two ferrocene groups by a hoop-shaped [10]cyclophenacene. The compounds exhibit two-electron oxidation and two-electron reduction behavior, generating dicationic and dianionic species. The two iron atoms interact with each other through the pi-conjugation of the cyclophenacene, as revealed by differential pulse voltammetric analysis of the D5d Fe2(C60Me10)Cp2.

The preferable photoconversion tunability of conjugated polymers (CPs) is of great interest in cancer phototherapy. However, very few molecular design strategies have been developed for achieving CPs with highly efficient photoconversion performance. Herein, a rational design of near-infrared (NIR) Pt-acetylide conjugated polymer CP3 with highly efficient photoconversion behaviors for synergistic photodynamic therapy (PDT) and photothermal therapy (PTT) was demonstrated. CP3 containing boron dipyrromethene (BDP) units displayed intense absorption peaks in the NIR region, which were red-shifted approximately 60 nm compared to the corresponding small-molecule precursor of BDP. Compared with control polymers CP1 and CP2, after the introduction of Pt into CP3, the triplet state, which benefits the generation of reactive oxygen species for photodynamic therapy, was identified clearly in both CP3 and the prepared CP3 nanoparticles (CP3-NPs) by ultrafast femtosecond transient absorption (fs-TA) spectroscopy. Notably, different from the traditional nonradiative decay channel with lifetime of 1.1 ps in CP3, CP3-NPs possess an additional nonradiative decay channel with lifetime of 10 ps, both of which contribute to the superior photothermal conversion effect upon 808 nm irrradiation. All these photoconversion performances lead to excellent tumor ablation. This study elucidates the excited-state dynamics in Pt-acetylide CPs, which provide an insightful understanding and valuable guidelines for the future design of high-performance theranostic agents based on CPs for synergistic cancer phototherapy.

BACKGROUND

Cognitive functions are highly heritable and polygenic, though the source of this genetic influence is unclear. On the neurobiological level, these functions rely on effective neuroplasticity, in which the activity-regulated cytoskeleton associated protein (ARC) plays an essential role.

OBJECTIVE

To examine whether the ARC gene complex may contribute to the genetic components of intellectual function given the crucial role of ARC in brain plasticity and memory formation.

METHODS

The ARC complex was tested for association with intelligence (IQ) in children from the Avon Longitudinal Study of Parents and Children (ALSPAC, N = 5,165). As Alzheimer's disease (AD) shares genetics with cognitive functioning, the association was followed up in an AD sample (17,008 cases, 37,154 controls).

RESULTS

The ARC complex revealed association with verbal and total IQ (empirical p = 0.027 and 0.041, respectively) in the ALSPAC. The strongest single variant signal (rs2830077; empirical p = 0.018), within the APP gene, was confirmed in the AD sample (p = 2.76E-03). Functional analyses of this variant showed its preferential binding to the transcription factor CP2.

CONCLUSIONS

This study implicates APP in childhood IQ. While follow-up studies are needed, this observation could help elucidate the etiology of disorders associated with cognitive dysfunction, such as AD.

This work inspects the supramolecular/molecular structures and digestion rate of potato starches (BEM, C7H, CP2 and CP4) as affected by starch biosynthetic enzymes. Among the starches, CP2 had a lower digestion rate with a higher paste heating stability. Regarding this, predominantly enzyme-sets (i) and (ii) were revealed to produce amylopectin chains. For CP2, the reduced activity ratio of starch-branching enzymes to soluble starch synthases allowed more long amylopectin chains (polymerization degree ≥ 34). Such molecular features tended to increase the crystallites and thicken the lamellae. With similar surface morphology and amylose content, the bulk density of chain packing in CP2 supramolecular structures could be increased. Then, there were an increase in the resistance of starch structures to hydrothermal effects, and a reduction in the enzyme hydrolysis rate. Also, the increased long amylopectin chains played roles in increasing the paste stability during heating with shearing and in reducing the digestion rate.

Reaction of (TBBP)AlMe⋅THF with [Cp*2 Zr(Me)OH] gave [(TBBP)Al(THF)-O-Zr(Me)Cp*2 ] (TBBP=3,3',5,5'-tetra-tBu-2,2'-biphenolato). Reaction of [DIPPnacnacAl(Me)-O-Zr(Me)Cp2 ] with [PhMe2 NH]+ [B(C6 F5 )4 ]- gave a cationic Al/Zr complex that could be structurally characterized as its THF adduct [(DIPPnacnac)Al(Me)-O-Zr(THF)Cp2 ]+ [B(C6 F5 )4 ]- (DIPPnacnac=HC[(Me)C=N(2,6-iPr2 -C6 H3 )]2 ). The first complex polymerizes ethene in the presence of an alkylaluminum scavenger but in the absence of methylalumoxane (MAO). The adduct cation is inactive under these conditions. Theoretical calculations show very high energy barriers (ΔG=40-47 kcal mol-1 ) for ethene insertion with a bridged AlOZr catalyst. This is due to an unfavorable six-membered-ring transition state, in which the methyl group bridges the metal and ethene with an obtuse metal-Me-C angle that prevents synchronized bond-breaking and making. A more-likely pathway is dissociation of the Al-O-Zr complex into an aluminate and the active polymerization catalyst [Cp*2 ZrMe]+ .

The novel, chemically stabilized disorazole analog, (-)-CP2-disorazole C1 (1) displayed potent anti-proliferative activity against a broad-spectrum of human colorectal cancer cells. HCT15 and H630R1 cell lines expressing high basal levels of the ABCB1 protein, known to cause multi-drug resistance, were also sensitive to growth inhibition by 1 but were resistant to both vincristine and docetaxel, two commonly used microtubule inhibitors. Compound 1 exhibited strong inhibition of tubulin polymerization at a level comparable to vincristine. In addition, treatment with 1 resulted in decreased protein levels of β-tubulin but not α-tubulin. An analysis of cellular proteins known to interact with microtubules showed that 1 caused decreased expression of c-Myc, APC, Rb, and additional key cellular signaling pathways in CRC cells. Treatment with compound 1 also resulted in G2/M cell cycle arrest and induction of apoptosis, but not senescence. Furthermore, endothelial spheroid sprouting assays demonstrated that 1 suppressed angiogenesis and can, therefore, potentially prevent cancer cells from spreading and metastasizing. Taken together, these findings suggest that the microtubule disruptor 1 may be a potential drug candidate for the treatment of mCRC.

Maize rayado fino virus (MRFV) is the type species of the genus Marafivirus in the family Tymoviridae. It infects maize (Zea mays), its natural host, to which it is transmitted by leafhoppers including Dalbulus maidis and Graminella nigrifrons in a persistent-propagative manner. The MRFV monopartite RNA genome encodes a precursor polyprotein that is processed into replication-associated proteins. The genome is encapsidated by two carboxy co-terminal coat proteins, CP1 and CP2. Cloned MRFV can be readily transmitted to maize by vascular puncture inoculation (VPI), and such virus systems that can be used in maize are valuable to examine plant gene function by gene silencing. However, the efficacy of marafiviruses for virus-induced gene silencing (VIGS) has not been investigated to date. To this end, MRFV genomic loci were tested for their potential to host foreign insertions without attenuating virus viability. This was done using infectious MRFV clones engineered to carry maize phytoene desaturase (PDS) gene fragments (ZmPDS) at various genomic regions. Several MRFV-PDS constructs were generated and tested for infectivity and VIGS in maize. This culminated in identification of the helicase/polymerase (HEL/POL) junction as a viable insertion site that preserved virus infectivity, as well as several sites at which sequence insertion caused loss of virus infectivity. Transcripts of viable constructs, carrying PDS inserts in the HEL/POL junction, induced stable local and systemic MRFV symptoms similar to wild-type infections, and triggered PDS VIGS initiating in veins and spreading into both inoculated and noninoculated leaves. These constructs were remarkably stable, retaining inserted sequences for at least four VPI passages while maintaining transmissibility by D. maidis. Our data thus identify the MRFV HEL/POL junction as an insertion site useful for gene silencing in maize.

Keywords: Dalbulus maidis; Zea mays; marafivirus.

Fetal hemoglobin (Hb F) is an important genetic modulator of the beta-hemoglobinopathies. The regulation of Hb F levels is influenced by transcription factors. We used phylogenetic footprinting to screen transcription factors that have binding sites in HBG1 and HBG2 genes' noncoding regions in order to know the genetic determinants of the Hb F expression. Our analysis showed 354 conserved motifs in the noncoding regions of HBG1 gene and 231 motifs in the HBG2 gene between the analyzed species. Of these motifs, 13 showed relation to Hb F regulation: cell division cycle-5 (CDC5), myelo-blastosis viral oncogene homolog (c-MYB), transcription factor CP2 (TFCP2), GATA binding protein 1 (GATA-1), GATA binding protein 2 (GATA-2), nuclear factor erythroid 2 (NF-E2), nuclear transcription factor Y (NF-Y), runt-related transcription factor 1 (RUNX-1), T-cell acute lymphocytic leukemia 1 (TAL-1), YY1 transcription factor (YY1), beta protein 1 (BP1), chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII), and paired box 1 (PAX-1). The last three motifs were conserved only in the noncoding regions of the HBG1 gene. The understanding of genetic elements involved in the maintenance of high Hb F levels may provide new efficient therapeutic strategies in the beta-hemoglobinopathies treatment, promoting reduction in clinical complications of these genetic disorders.

During the spring of 2019, distinct virus-like symptoms were observed in the Kafr El-Sheikh Governorate in Egypt in naturally infected eggplants. Leaves of affected plants showed interveinal leaf chlorosis, net yellow, chlorotic sectors, mottling, blisters, vein enation, necrotic intervention, and narrowing symptoms. The Alfalfa mosaic virus (AMV) was suspected of to be involved in this disease. Forty plant samples from symptomatic eggplants and 10 leaf samples with no symptoms were collected. The samples were tested by double antibody sandwich ELISA (DAS-ELISA) using AMV-IgG. Six of the 40 symptomatic leaf samples tested positive for AMV, while, DAS-ELISA found no AMV in the 10 leaf samples without symptoms. The AMV Egyptian isolate (AMV-Eggplant-EG) was biologically isolated from the six positive samples tested by DAS-ELISA and from the similar local lesions induced on Chenopodium amaranticolor and then re-inoculated in healthy Solanum melongena as a source of AMV-Eggplant-EG and confirmed by DAS-ELISA. Reverse transcription polymerase chain reaction (RT-PCR) assay with a pair of primers specific for coat protein (CP) encoding RNA 3 of AMV yielded an amplicon of 666 bp from infected plants of Solanum melongena with AMV-Eggplant-EG. The amplified PCR product was cloned and sequenced. Analysis of the AMV-Eggplant-EG sequence revealed 666 nucleotides (nt) of the complete CP gene (translating 221 amino acid (aa) residues). Analysis of phylogeny for nt and deduced aa sequences of the CP gene using the maximum parsimony method clustered AMV-Eggplant-EG in the lineage of Egyptian isolates (shark-EG, mans-EG, CP2-EG, and FRE-EG) with a high bootstrap value of 88% and 92%, respectively. In addition to molecular studies, melatonin (MTL) and salicylic acid (SA) (100 μM) were used to increase the resistance of eggplant to AMV- infection. Foliar spray with MLT and SA caused a significant increase in the morphological criteria (shoot, root length, number of leaves, leaf area, and leaf biomass), chlorophyll and carotenoid content, antioxidant enzymes, and gene expression of some enzymes compared to the infected plants. On the other hand, treatment with MLT and SA reduced the oxidative damage caused by AMV through the reduction of hydrogen peroxide, superoxide anions, hydroxyl radicals, and malondialdehyde. In conclusion, MLT and SA are eco-friendly compounds and can be used as antiviral compounds.

Keywords: AMV; RT-PCR; antioxidant enzymes; eggplant; gene expression; immunity boosting; oxidative damage; sequencing.

OBJECTIVE

To study the clinical pathological characteristics and high risk factors for borderline ovarian tumor (BOT) and stage I epithelial ovarian cancer (EOC).

METHODS

A total of 91 patients with BOT and 52 patients with stage IEOC who were diagnosed and treated in the Department of Gynecology, Peking University People's Hospital from November 2002 to May 2010 were recruited in this study. The patients' clinical characteristics were reviewed respectively and compared between the two groups.

RESULTS

The women in BOT group were significantly younger than those in EOC group (41.16 ± 14.95 vs. 50.90 ± 14.37,P<0.01). Compared with women with BOT, women with EOC were more likely to be post-menopausal(42.3% vs. 23.1%,P=0.016) and more with family history of malignant tumors (26.9% vs. 13.2%,P=0.04).There were no significant differences in the size of tumors and the serum level of tumor markers. But the size of solid portion of the tumor of EOC was significantly larger than that of BOT(P<0.01). The extent of the increase of CP2 among the patients with EOC was higher than that among the patients with BOT(256.99 vs. 116.59, P=0.028). There was a statistically significant difference between the two groups in tumors' histopathological type(P<0.01). The serous and mucous tumors were more common in EOC group (90.1%, 82/91). In contrary, endometrioid, clear cells and mixed epithelial cancers were more common in EOC group than serous and mucous cancers (44.2%, 23/52).

CONCLUSIONS

Although the clinical presentation of patients with stage I EOC was similar to that of those with BOT, there were significant differences in the patients' age, post-menopausal or not, family history of malignant tumors, size of solid portion of tumors, extent of the increase of the tumor biomarker, especially of CP2 and tumors histopathological type. These clinicopathological characteristics might be helpful for us to make different diagnosis.

Purpose: Continuous incremental protocols (CP) may misestimate the maximum aerobic velocity (V_max) due to increases in running speed faster than cardiorespiratory/metabolic adjustments. A higher aerobic capacity may mitigate this issue due to faster pulmonary oxygen uptake ([Formula: see text]O₂) kinetics. Therefore, this study aimed to compare three different protocols to assess V_max in athletes with higher or lower training status.

Methods: Sixteen well-trained runners were classified according to higher (HI) or lower (LO) [Formula: see text]O_2max [Formula: see text]O₂-kinetics was calculated across four 5-min running bouts at 10 km·h^-1. Two CPs [1 km·h^-1 per min (CP1) and 1 km·h^-1 every 2-min (CP2)] were performed to determine V_max [Formula: see text]O_2max, lactate-threshold and submaximal [Formula: see text]O₂/velocity relationship. Results were compared to the discontinuous incremental protocol (DP).

Results: V_max, [Formula: see text]O_2max, [Formula: see text]CO₂ and VE were higher [(P < 0.05,(ES:0.22/2.59)] in HI than in LO. [Formula: see text]O₂-kinetics was faster [P < 0.05,(ES:-2.74/ - 1.76)] in HI than in LO. [Formula: see text]O₂/velocity slope was lower in HI than in LO [(P < 0.05,(ES:-1.63/ - 0.18)]. V_max and [Formula: see text]O₂/velocity slope were CP1 > CP2 = DP for HI and CP1 > CP2 > DP for LO. A lower [P < 0.05,(ES:0.53/0.75)] V_max-difference for both CP1 and CP2 vs DP was found in HI than in LO. V_max-differences in CP1 vs DP showed a large inverse correlation with V_max, [Formula: see text]O_2max and lactate-threshold and a very large correlation with [Formula: see text]O₂-kinetics.

Conclusions: Higher aerobic training status witnessed by faster [Formula: see text]O₂ kinetics led to lower between-protocol V_max differences, particularly between CP2 vs DP. Faster kinetics may minimize the mismatch issues between metabolic and mechanical power that may occur in CP. This should be considered for exercise prescription at different percentages of V_max.

Keywords: Aerobic capacity; Incremental test; Maximal aerobic power; Maximum oxygen uptake; O2 kinetics; Running velocity.

Introduction: Bilateral spastic cerebral palsy (BSCP) is the most common subtype of cerebral palsy (CP), which is characterized by various motor and cognitive impairments, as well as emotional instability. However, the neural basis of these problems and how repetitive transcranial magnetic stimulation (rTMS) can make potential impacts on the disrupted structural brain network in BSCP remain unclear. This study was aimed to explore the topological characteristics of the structural brain network in BSCP following the treatment of rTMS. Methods: Fourteen children with BSCP underwent 4 weeks of TMS and 15 matched healthy children (HC) were enrolled. Diffusion tensor imaging (DTI) data were acquired from children with bilateral spastic cerebral palsy before treatment (CP1), children with bilateral spastic cerebral palsy following treatment (CP2) and HC. The graph theory analysis was applied to construct the structural brain network. Then nodal clustering coefficient (C _i ) and shortest path length (L _i ) were measured and compared among groups. Results: Brain regions with significant group differences in C _i were located in the left precental gyrus, middle frontal gyrus, calcarine fissure, cuneus, lingual gyrus, postcentral gyrus, inferior parietal gyri, angular gyrus, precuneus, paracentral lobule and the right inferior frontal gyrus (triangular part), insula, posterior cingulate gyrus, precuneus, paracentral lobule, pallidum. In addition, significant differences were detected in the L _i of the left precental gyrus, lingual gyrus, superior occipital gyrus, middle occipital gyrus, superior parietal gyrus, precuneus and the right median cingulate gyrus, posterior cingulate gyrus, hippocampus, putamen, thalamus. Post hoc t-test revealed that the CP2 group exhibited increased C _i in the right inferior frontal gyrus, pallidum and decreased L _i in the right putamen, thalamus when compared with the CP1 group. Conclusion: Significant differences of node-level metrics were found in various brain regions of BSCP, which indicated a disruption in structural brain connectivity in BSCP. The alterations of the structural brain network provided a basis for understanding of the pathophysiological mechanisms of motor and cognitive impairments in BSCP. Moreover, the right inferior frontal gyrus, putamen, thalamus could potentially be biomarkers for predicting the efficacy of TMS.

Keywords: cerebral palsy; diffusion tensor imaging; graph theory; repetitive transcranial magnetic stimulation; structural brain network.