Absence or reduction of Fhit expression in most clear cell renal carcinomas

The FHIT gene at human chromosome region 3p14.2 straddles the common fragile site, FRA3B, and numerous homozygous deletions in cancer cell lines and primary tumors. Also, the 3p14.2 chromosome breakpoint of the familial clear cell kidney carcinoma-associated translocation, t(3;8)(p14.2;q24), disrupts one FHIT allele between exons 3 and 4, fulfilling one criterion for a familial tumor suppressor gene: that one allele is constitutionally inactivated. Because the FHIT gene sustains biallelic intragenic deletions rather than mutations, there has not been evidence that the FHIT gene frequently plays a role in kidney cancer, although replacement of Fhit expression in a Fhit-negative renal carcinoma cell line suppressed tumor growth in nude mice. We have now assessed 41 clear cell renal carcinomas for expression of Fhit by immunohistochemistry. Normal renal tubule epithelial cells express Fhit uniformly and strongly, whereas 51% of the tumors are completely negative, 34% of tumors show a mixture of positive and negative cells, and 14% are uniformly positive, although usually less strongly positive than the normal epithelial cells. Most interestingly, there was a correlation between complete absence of Fhit and the G1 morphological grade and early clinical stage. Morphological grades G2 and G3 exhibited a mixture of positive and negative cells with a tendency for a higher fraction of negative cells in G3. Fhit inactivation is likely to be an early event in G1 tumors and may be associated with progression in G2 and G3 tumors.     

s-Wave vs.d -Wave Superconductivity in the Two-Dimensional Hubbard Model

The anisotropic superconductivity has been considered in the two-dimensional Hubbard model. We allow for on and off-site intralayer Cooper pairs. Interlayer momentum-conserving Josephson tunneling which couples adjacent layers has been taken into account. The meanfield solution for the superconducting transition temperature demonstrates the competition between local Coulomb repulsion and interlayer tunneling in thes-wave channel. This competition leads to the mixedsd superconducting state at low doping. We also demonstrate thatc-phonon-assisted transitions between intra and interlayer states can effectively give rise to momentum-conserving Josephson tunneling.     

Temperature dependence of surface tension of poly(vinyl chloride)

The thermal dependence of the surface tension of poly(vinyl chloride) (PVC) containing typical additives was determined below the glass transition temperature. From the results, the surface tension of PVC melts was evaluated and possible differences between the real value and estimate are discussed. It is suggested that the surface tension does not affect the wall-slipping properties of PVC melts.     

Antipsychotic- and Anxiolytic-like Properties of a Multimodal Compound JJGW08 in Rodents

Schizophrenia is a chronic mental illness, which remains difficult to treat. A high resistance to the available therapies, their insufficient efficacy, and numerous side effects are the reasons why there is an urgent need to develop new antipsychotics. This study aimed to assess the antipsychotic-like effects of JJGW08, a novel arylpiperazine alkyl derivative of salicylamide, in rodents. First, considering the JJGW08 receptor profile, we investigated the compound’s intrinsic activity towards dopamine D₂ and serotonin 5-HT_1A, 5-HT_2A, and 5-HT₇ receptors using functional assays. Next, we assessed the effect of JJGW08 on MK-801- and amphetamine-induced hyperlocomotion, its risk of inducing catalepsy and impairing motor coordination, as well as the anxiolytic-like effects in the four-plate and marble burying tests in mice. Finally, we investigated the antipsychotic-like properties of JJGW08 in rats using MK-801-induced hyperlocomotion and prepulse inhibition tests. We found that JJGW08 showed antagonistic properties at dopamine D₂ and serotonin 5-HT_1A, 5-HT_2A, and 5-HT₇ receptors. However, the effect on the 5-HT_2A and 5-HT₇ receptors was very weak. Moreover, the tested compound showed an antipsychotic-like effect in MK-801- and amphetamine-induced hyperlocomotion but not in a prepulse inhibition test in rats. Notably, JJGW08 demonstrated anxiolytic-like properties in both behavioral tests. Importantly, the compound did not induce catalepsy or motor coordination impairment in mice at antipsychotic-like doses. Our study suggests it is worth searching for new potential antipsychotics among arylpiperazine alkyl derivatives of salicylamide.     

Magnesium-Catalyzed Asymmetric Thia-Michael Addition to α,β-Unsaturated Ketones

We demonstrate the application of chiral magnesium complexes in an asymmetric carbon-sulfur bond-forming reaction. Enantioselective and cost-effective methodology under mild condition for the thia-Michael addition, utilizing an in situ generated chiral dinuclear magnesium-ProPhenol complex, has been developed. The versatility of this protocol is demonstrated with a broad range of thiol nucleophiles and a wide selection of enones. Enantioenriched β-ketosulfides are obtained in good to excellent yields and moderate to excellent enantioselectivity. The presented catalytic system exhibits excellent tolerance for structurally different substrates while maintaining high enantioselectivity. This observation aligns with proposed mechanism, wherein the sulfur atom coordinates to the catalyst in close proximity to the reaction center.     

Analysis of the Site-Specific Myoglobin Modifications in the Melibiose-Derived Novel Advanced Glycation End-Product

MAGE (melibiose-derived advanced glycation end-product) is the glycation product generated in the reaction of a model protein with melibiose. The in vivo analog accumulates in several tissues; however, its origin still needs explanation. In vitro MAGE is efficiently generated under dry conditions in contrast to the reaction carried in an aqueous solvent. Using liquid chromatography coupled with mass spectrometry, we analyzed the physicochemical properties and structures of myoglobin glycated with melibiose under different conditions. The targeted peptide analysis identified structurally different AGEs, including crosslinking and non-crosslinking modifications associated with lysine, arginine, and histidine residues. Glycation in a dry state was more efficient in the formation of structures containing an intact melibiose moiety (21.9%) compared to glycation under aqueous conditions (15.6%). The difference was reflected in characteristic fluorescence that results from protein structural changes and impact on a heme group of the model myoglobin protein. Finally, our results suggest that the formation of in vitro MAGE adduct is initiated by coupling melibiose to a model myoglobin protein. It is confirmed by the identification of intact melibiose moieties. The intermediate glycation product can further rearrange towards more advanced structures, including cross-links. This process can contribute to a pool of AGEs accumulating locally in vivo and affecting tissue biology.     

Congo Red as a Supramolecular Carrier System for Doxorubicin: An Approach to Understanding the Mechanism of Action

The uptake and distribution of doxorubicin in the MCF7 line of breast-cancer cells were monitored by Raman measurements. It was demonstrated that bioavailability of doxorubicin can be significantly enhanced by applying Congo red. To understand the mechanism of doxorubicin delivery by Congo red supramolecular carriers, additional monolayer measurements and molecular dynamics simulations on model membranes were undertaken. Acting as molecular scissors, Congo red particles cut doxorubicin aggregates and incorporated them into small-sized Congo red clusters. The mixed doxorubicin/Congo red clusters were adsorbed to the hydrophilic part of the model membrane. Such behavior promoted transfer through the membrane.     

ERAP/HLA-C and KIR Genetic Profile in Couples with Recurrent Implantation Failure

Proper embryo implantation depends on the tolerance of the maternal immune system to the fetus and its foreign paternal antigens. During implantation and early pregnancy, the dominant leukocytes in the uterus are uterine NK cells, expressing killer immunoglobulin-like receptors (KIR). KIRs recognize human leukocyte antigens (HLA-C) on the human trophoblast inherited from the father and mother. The antigenic peptides presented by the HLA are formed via their cleavage by endoplasmic reticulum aminopeptidases ERAP1 and ERAP2. The aim of this study was to assess the association of combined KIR genes and their HLA-C ligands, as well as ERAP1 and ERAP2 polymorphisms with recurrent implantation failure after in vitro fertilization (RIF). We tested 491 couples who underwent in vitro fertilization (IVF) and 322 fertile couples. Genotype CC rs27044 ERAP1 in female with a male’s HLA-C1C1 or HLA-C1C2 protected from RIF (p/p_corr. = 0.005/0.044, OR = 0.343; p/p_corr. = 0.003/0.027, OR = 0.442, respectively). Genotype TT rs30187 ERAP1 in female with a male’s HLA-C1C2 genotype increased the risk of RIF. Summarizing, in the combination of female ERAP1 and an HLA-C partner, the rs30187 C>T and rs27044 C>G polymorphisms play an important role in implantation failure.     

Colossal negative magnetoresistance from hopping in insulating ferromagnetic semiconductors

Ferromagnetic semiconductor Ga_1–xMn_xAs_1–yP_y thin films go through a metal–insulator transition at low temperature where electrical conduction becomes driven by hopping of charge carriers. In this regime, we report a colossal negative magnetoresistance (CNMR) coexisting with a saturated magnetic moment, unlike in the traditional magnetic semiconductor Ga_1–xMn_xAs. By analyzing the temperature dependence of the resistivity at fixed magnetic field, we demonstrate that the CNMR can be consistently described by the field dependence of the localization length, which relates to a field dependent mobility edge. This dependence is likely due to the random environment of Mn atoms in Ga_1–xMn_xAs_1–yP_y which causes a random spatial distribution of the mobility that is suppressed by an increasing magnetic field.