A new mutation affecting FRQ-less rhythms in the circadian system of Neurospora crassa

We are using the fungus Neurospora crassa as a model organism to study the circadian system of eukaryotes. Although the FRQ/WCC feedback loop is said to be central to the circadian system in Neurospora, rhythms can still be seen under many conditions in FRQ-less (frq knockout) strains. To try to identify components of the FRQ-less oscillator (FLO), we carried out a mutagenesis screen in a FRQ-less strain and selected colonies with altered conidiation (spore-formation) rhythms. A mutation we named UV90 affects rhythmicity in both FRQ-less and FRQ-sufficient strains. The UV90 mutation affects FRQ-less rhythms in two conditions: the free-running long-period rhythm in choline-depleted chol-1 strains becomes arrhythmic, and the heat-entrained rhythm in the frq(10) knockout is severely altered. In a FRQ-sufficient background, the UV90 mutation causes damping of the free-running conidiation rhythm, reduction of the amplitude of the FRQ protein rhythm, and increased phase-resetting responses to both light and heat pulses, consistent with a decreased amplitude of the circadian oscillator. The UV90 mutation also has small but significant effects on the period of the conidiation rhythm and on growth rate. The wild-type UV90 gene product appears to be required for a functional FLO and for sustained, high-amplitude rhythms in FRQ-sufficient conditions. The UV90 gene product may therefore be a good candidate for a component of the FRQ-less oscillator. These results support a model of the Neurospora circadian system in which the FRQ/WCC feedback loop mutually interacts with a single FLO in an integrated circadian system.     

PPAR-γ: Its ligand and its regulation by microRNAs

Peroxisome proliferator-activated receptors (PPARs) belong to the nuclear receptor superfamily. PPARs are categorized into three subtypes, PPARα, β/δ, and γ, encoded by different genes, expressed in diverse tissues and participate in various biological functions and can be activated by their metabolic derivatives in the body or dietary fatty acids. The PPAR-γ also takes parts in the regulation of energy balance, lipoprotein metabolism, insulin sensitivity, oxidative stress, and inflammatory signaling. It has been implicated in the pathology of numerous diseases including obesity, diabetes, atherosclerosis, and cancers. Among various cellular and molecular targets that are able to regulate PPAR-γ and its underlying pathways, microRNAs (miRNAs) appeared as important regulators. Given that the deregulation of these molecules via targeting PPAR-γ could affect initiation and progression of various diseases, identification of miRNAs that affects PPAR-γ could contribute to the better understanding of roles of PPAR-γ in various biological and pathological conditions. Here, we have summarized the function and various ligands of PPAR-γ and have highlighted various miRNAs involved in the regulation of PPAR-γ.     

Low representation of Fc receptor-like 1–5 molecules in leukemic cells from Iranian patients with acute lymphoblastic leukemia

Recent studies have demonstrated expression of Fc receptor-like (FCRL) molecules, a newly identified family with preferential B-cell lineage expression, in some chronic B-cell leukemias with possible implication for classification and/or targeted immunotherapy. In this study, the expression pattern of FCRL1-5 genes was studied in 73 Iranian ALL patients and 35 normal subjects using semi-quantitative RT-PCR method. FCRL protein expression was also investigated by flow cytometry. Our results indicate significant down-regulation of all FCRL genes in ALL compared to normal subjects. Although, FCRL mRNA expression was almost exclusively confined to normal isolated B-cells compared to T-cells, but these genes were similarly expressed in B-ALL, T-ALL and different B-ALL immunophenotypic subtypes. Surface protein expression of FCRL1, 2, 4, and 5 molecules in 10 ALL and 5 normal samples confirmed the PCR results. Expression profile of FCRL molecules in different subtypes of ALL argues against their potential implication as suitable targets for classification and/or immunotherapy of ALL. T. Kazemi, H. Asgarian-Omran and A. Memarian have contributed equally to this study.     

Synthesis and characterization of modified starch hydrogels for photodynamic treatment of cancer

The objective of the present study was to develop carboxymethyl starch (CMS) and dextran sulfate (DS) hydrogels that are able to efficiently encapsulate 5-,10-,15-,20-tetrakis(meso-hydroxyphenyl)porphyrin (mTHPP), a porphyrin-based PS agent. The study showed that the lifetime of the triplet state for porphyrin PS is significantly increase when encapsulate into hydrogel. In addition to the possible enhancement of (1)O(2) generation, other advantages to incorporating porphyrin-based PS agents into hydrogel include the ability to solubilize these generally hydrophobic agents, the small and uniform size of hydrogels, and potential for passive targeting of solid tumors via the enhanced permeation and retention effect decreasing systemic photosensitization. This novel type of carboxymethyl starch (CMS) hydrogel using dextran sulfate (DS) as a polyanionic polymer was developed to achieve complex coacervation for the incorporation and controlled release of an anti-angiogenesis hexapeptide, this was the first report describing the use of DS to formulate CMS based hydrogels.     

Interactive relationship between Trp metabolites and gut microbiota: The impact on human pathology of disease

Tryptophan (Trp), an α-amino acid, is the precursor of serotonin (5-hydroxytryptamine, 5-HT), which is involved in a variety of features of metabolic function and human nutrition. Evidence highlights the role of Trp metabolites (exclusively 5-HT) in the gastrointestinal (GI) tract; however, the mechanisms of action involved in the release of 5-HT in the GI tract are still unknown. Considering the fact that variations of 5-HT may facilitate the growth of certain GI disorders, gaining a better understanding of the function and release of 5-HT in the GI tract would be beneficial. Additionally, investigating Trp metabolism may clarify the relationship between Trp and gut microbiota. It is believed that other metabolites of Trp (mostly that of the kynurenine pathway) may play a significant role in controlling gut microbiota function. In this review, we have attempted to summarize the current research investigating the relationship of gut microbiota, Trp and 5-HT metabolism (with particular attention paid to their metabolite type, as well as a discussion of the research methods used in each study). Taking together, regarding the role that Trp/5-HT plays in a range of physical and mental diseases, the gut bacterial types, as well as the related disorders, have been exclusively considered.     

The influence of the catalyst preparation protocol and silane structure on the rate and enantioselectivity of ansa-titanocene catalysed hydrosilation of prochiral ketones

The hydrosilation of prochiral ketones using catalysts prepared by alkylation of [1,2-bis(tetrahydroindenyl)ethane]titanium^IV(1,1′-binaphth-2,2′-diolate) with MeLi and n-BuLi, and (EtO)₃SiH, Me(EtO)₂SiH, [MeSi(H)O]₄, Me₃SiO[MeSi(H)O]_nSiMe₃ and MeSiH₃ as the hydrosilane is described. The rates obtained with the MeLi based catalyst are one to two orders of magnitude faster than previously observed with MeLi based catalysts in the presence of MePhSiH₂ and Ph₂SiH₂ and about the same as those observed with n-BuLi based catalysts. Me(EtO)₂SiH, [MeSi(H)O]₄ and Me₃SiO[MeSi(H)O]_nSiMe₃ all undergo rapid redistribution in the presence of the catalyst to give MeSiH₃, the actual hydrosilating agent in all three cases. Likewise, (EtO)₃SiH redistributes to SiH₄. The ee's for the hydrosilation product of acetophenone are consistently much higher (99%) for the n-BuLi based catalyst than for the MeLi based catalyst (40–50%). The hydride complex [(BTHIE)TiH]₂ gives essentially the same enantioselectivity as the MeLi based catalyst. The ee's for a test set of dialkylketones are relatively insensitive to either the catalyst or the hydrosilane. Some possible mechansims that are consistent with the experimental results are discussed.     

Mecamylamine blocks the burning sensation of nicotine on the tongue

This study demonstrated the probability of nicotinic cholinergicreceptors in the sensory nerves of the tongue. Subjects, testedon two occasions, evaluated the intensity of the burning sensationof 0.12% (7.4 mM) nicotine or a water control. Pretreatmentof the tongue with 0.075% (4.5 mM) mecamylamine, a nicotiniccholinergic receptor Mocker, resulted in significantly lowermagnitude estimates than similar pretreatment with water. Theseresults suggest that the burning sensation from nicotine isat least partly mediated by cholinergic receptors.     

Diversolides A-G, guaianolides from the roots of Ferula diversivittata

Seven sesquiterpene lactone derivatives, diversolides A-G (1-7), together with two known compounds, diversin (8) and stigmasterol, were isolated from the roots of Ferula diversivittata. The structures of these compounds were elucidated by extensive spectroscopic methods including 1D-(¹H and ¹³C) and 2D-NMR experiments (DQF-COSY, HSQC, HMBC, and NOESY) as well as high-resolution EIMS. Compounds 1, 4 and 6-8 were tested for their in vitro antifungal and antibacterial activities. Some of the tested compounds showed moderate antifungal and antibacterial activities with minimum inhibitory concentration (MIC) values from 40 to 80 μg/ml.