Disrupted-in-Schizophrenia 1 (DISC1) Overexpression and Juvenile Immune Activation Cause Sex-Specific Schizophrenia-Related Psychopathology in Rats

Synaptic pruning is a critical refinement step during neurodevelopment, and schizophrenia has been associated with overpruning of cortical dendritic spines. Both human studies and animal models implicate disrupted-in-schizophrenia 1 (DISC1) gene as a strong susceptibility factor for schizophrenia. Accumulating evidence supports the involvement of DISC1 protein in the modulation of synaptic elimination during critical periods of neurodevelopment and of dopamine D2-receptor-mediated signaling during adulthood. In many species, synaptic pruning occurs during juvenile and adolescent periods and is mediated by microglia, which can be over-activated by an immune challenge, giving rise to overpruning. Therefore, we sought to investigate possible interactions between a transgenic DISC1 model (tgDISC1) and juvenile immune activation (JIA) by the bacterial cell wall endotoxin lipopolysaccharide on the induction of schizophrenia-related behavioral and neurochemical disruptions in adult female and male rats. We examined possible behavioral aberrations along three major symptom dimensions of schizophrenia including psychosis, social and emotional disruptions, and cognitive impairments. We detected significant gene–environment interactions in the amphetamine-induced locomotion in female animals and in the amphetamine-induced anxiety in male animals. Surprisingly, gene–environment interactions improved social memory in both male and female animals. JIA alone disrupted spatial memory and recognition memory, but only in male animals. DISC1 overexpression alone induced an improvement in sensorimotor gating, but only in female animals. Our neurochemical analyses detected sex- and manipulation-dependent changes in the postmortem monoamine content of animals. Taken together, we here report sex-specific effects of environment and genotype as well as their interaction on behavioral phenotypes and neurochemical profiles relevant for schizophrenia

A Cryogenic Silicon Interferometer for Gravitational-wave Detection

The detection of gravitational waves from compact binary mergers by LIGO has opened the era of gravitational wave astronomy, revealing a previously hidden side of the cosmos. To maximize the reach of the existing LIGO observatory facilities, we have designed a new instrument able to detect gravitational waves at distances 5 times further away than possible with Advanced LIGO, or at greater than 100 times the event rate. Observations with this new instrument will make possible dramatic steps toward understanding the physics of the nearby Universe, as well as observing the Universe out to cosmological distances by the detection of binary black hole coalescences. This article presents the instrument design and a quantitative analysis of the anticipated noise floor

A Cryogenic Silicon Interferometer for Gravitational-wave Detection

The detection of gravitational waves from compact binary mergers by LIGO has opened the era of gravitational wave astronomy, revealing a previously hidden side of the cosmos. To maximize the reach of the existing LIGO observatory facilities, we have designed a new instrument that will have 5 times the range of Advanced LIGO, or greater than 100 times the event rate. Observations with this new instrument will make possible dramatic steps toward understanding the physics of the nearby universe, as well as observing the universe out to cosmological distances by the detection of binary black hole coalescences. This article presents the instrument design and a quantitative analysis of the anticipated noise floor

Behandlung der Polyomavirus Nephritis nach Nierentransplantation mit Cidofovir

The polyomavirus-associated nephropathy (PVAN) affects up to 10 % of kidney transplant patients and involves a 50 % risk of transplant failure. No consensus guideline exists how to treat the PVAN. Cidofovir (CV) has long been proposed but it has an unknown antiviral effect in PVAN. 7 Patients with biopsy proven PVAN 5 month to 2 years after kidney transplantation were observed. All Patients received different immunosuppressive drugs; Six of the 7 patients were treated with low dose CV(1.0 - 0.25 mg/kg)without probenecid. One of the 7 patients was treated with reduced immunosuppressive regimen alone and switched from tacrolimus to everolimus (EVR). The serum creatinine (sCR) was taken as measure of the transplant function; the blood viral load was measured for treatment monitoring. In 4 of the 6 CV treated patients the quantified viral load decreased in serum. In one of the other patients polyoma virus completely disappeared in urine and one CV patient had a negative control biopsy. In the last patient with reduction of immunosuppression alone and switching to EVR the viral load decreased without rejection. The mean sCR increased after CV treatment and repetitive transplant biopsy disclosed signs of nephrotoxicity in three cases. Three patients lost their transplant function, but in four cases the transplant function could be preserved. Two of the CV treated patients had signs of myelotoxicity. Two of the patients had an increase of the viral load after termination of the CV treatment; after reduction of immunosuppression, they had a beneficial outcome. CV has a clear antiviral effect but CV use is associated with the risk of nephrotoxicity. Withholding probenecid might increase the risk of myelotoxicity. Future patients could benefit from even lower dose CV with concurrent reduction of immunosuppression

Catalyst Activation and Influence of the Oil Matrix on Extractive Oxidative Desulfurization Using Aqueous Polyoxometalate Solutions and Molecular Oxygen

Our contribution describes the oxidative desulfurization of dibenzothiophene (DBT) from model oils using an aqueous H8PV5Mo7O40 (HPA-5) catalyst solution and molecular oxygen as the oxidant. In contrast to common oxidative desulfurization (ODS) protocols, the organic sulfur compound DBT is oxidized to water-soluble compounds, such as sulfuric acid (50–55%), sulfoacetic acid (20–25%), and sulfobenzoic acid (25–30%), which are extracted in situ into the aqueous catalyst phase. We describe the activating effect of oxalic acid on the ODS performance of the catalyst and propose a mechanism for the catalyst activation. Moreover, we report on the influence of various organic solvents, i.e., n-alkanes and aromatics, on the oxidative DBT removal. Remarkably, the rate of DBT oxidation and removal enhances with an increasing chain length of the alkane matrix, whereas aromatic compounds in the oil matrix inhibit the desulfurization rate. Moreover, we demonstrate that the aqueous catalyst phase can be reused at least 5 times without loss in catalytic performance

Extraction Coupled Oxidative Desulfurization of Fuels to Sulfate and Water-Soluble Sulfur Compounds Using Polyoxometalate Catalysts and Molecular Oxygen

Our contribution demonstrates a new way of fuel desulfurization, namely selective oxidation of organic S-compounds present in fuels to water-soluble sulfur compounds followed by in situ extraction of the latter into an aqueous phase. Different from common oxidative desulfurization (ODS) processes, we demonstrate a technique that converts sulfur compounds in fuel to a large extent to sulfate (60–70%) using oxygen as the oxidant and an aqueous H$_{8}$P$_{5}$VMo$_{7}$O$_{40}$ (HPA-5) solution as the catalyst phase. Other water-soluble desulfurization products are sulfoacetic acid (SAA) with a share of 10–20%, 2-sulfobenzoic acid (2-SBA), and 2-(sulfooxy)benzoic acid (2-SOBA), the latter two with a share of <10%. The new desulfurization method has been optimized for removing benzothiophene from isooctane, giving the best results with a degree of desulfurization of 99% applying 120 °C, 20 bar oxygen pressure, and 1000 rpm of 6 h reaction time using a volume water/oil ration of 10/1. Furthermore, we also successfully demonstrated the desulfurization of a domestic fuel oil with 973 ppmw sulfur content with a degree of desulfurization of 28% under nonoptimized conditions