Seven new genes designated dsrLJOPNSR were identified immediately downstream of dsrABEFHCMK, completing the dsr gene cluster of the phototrophic sulfur bacterium Allochromatium vinosum D (DSM 180 T ). Interposon mutagenesis proved an essential role of the encoded proteins for the oxidation of intracellular sulfur, an obligate intermediate during the oxidation of sulfide and thiosulfate. While dsrR and dsrS encode cytoplasmic proteins of unknown function, the other genes encode a predicted NADPH:acceptor oxidoreductase (DsrL), a triheme c-type cytochrome (DsrJ), a periplasmic iron-sulfur protein (DsrO), and an integral membrane protein (DsrP). DsrN resembles cobyrinic acid a,c-diamide synthases and is probably involved in the biosynthesis of siro(heme)amide, the prosthetic group of the dsrAB-encoded sulfite reductase. The presence of most predicted Dsr proteins in A. vinosum was verified by Western blot analysis. With the exception of the constitutively present DsrC, the formation of Dsr gene products was greatly enhanced by sulfide. DsrEFH were purified from the soluble fraction and constitute a soluble ␣ 2 ␤ 2 ␥ 2 -structured 75-kDa holoprotein. DsrKJO were purified from membranes pointing at the presence of a transmembrane electron-transporting complex consisting of DsrKMJOP. In accordance with the suggestion that related complexes from dissimilatory sulfate reducers transfer electrons to sulfite reductase, the A. vinosum Dsr complex is copurified with sulfite reductase, DsrEFH, and DsrC. We therefore now have an ideal and unique possibility to study the interaction of sulfite reductase with other proteins and to clarify the long-standing problem of electron transport from and to sulfite reductase, not only in phototrophic bacteria but also in sulfate-reducing prokaryotes.Phototrophic purple and green sulfur-oxidizing bacteria use sulfur compounds as electron donors for reductive carbon dioxide fixation during photolithotrophic growth (7, 10). In these organisms, light energy is used to transfer electrons from sulfur compounds to the level of the more highly reducing electron carriers NAD(P) ϩ and ferredoxin. In our laboratory we seek to understand oxidative sulfur metabolism in anoxygenic phototrophic bacteria by using the genetically accessible ␥-proteobacterium Allochromatium vinosum (formerly Chromatium vinosum [34]) as our model organism. It is a purple sulfur bacterium belonging to the family Chromatiaceae. A. vinosum carries out the complete eight-electron oxidations of sulfide and thiosulfate to sulfate. Intracellularly stored sulfur globules are an obligate intermediate in the process (57). The sulfur in the globules is present in the molecular structure of sulfur chains (58) and is enclosed by a protein envelope, a feature shared by most if not all of the chemotrophic sulfur-oxidizing bacteria that form intracellular sulfur globules (9, 14, 51). Topologically, the sulfur globules of A. vinosum and probably of other members of the Chromatiaceae are located extracytoplasmically, in the periplasm (51).O...

Alzheimer's disease (AD) is a neurodegenerative disorder primarily affecting regions of the brain responsible for higher cognitive functions. Immunization against ␤-amyloid (A␤) in animal models of AD has been shown to be effective on the molecular level but also on the behavioral level. Recently, we reported naturally occurring autoantibodies against A␤ (NAbs-A␤) being reduced in Alzheimer's disease patients. Here, we further investigated their physiological role: in epitope mapping studies, NAbs-A␤ recognized the mid-/Cterminal end of A␤ and preferentially bound to oligomers but failed to bind to monomers/fibrils. NAbs-A␤ were able to interfere with A␤ peptide toxicity, but NAbs-A␤ did not readily clear senile plaques although early fleecy-like plaques were reduced. Administration of NAbs-A␤ in transgenic mice improved the object location memory significantly, almost reaching performance levels of wild-type control mice. These findings suggest a novel physiological mechanism involving NAbs-A␤ to dispose of proteins or peptides that are prone to forming toxic aggregates.

Internet and computer game addiction represent a growing mental health concern, acknowledged by the World Health Organization.OBJECTIVE To determine whether manualized cognitive behavioral therapy (CBT), using short-term treatment for internet and computer game addiction (STICA), is efficient in individuals experiencing internet and computer game addiction. DESIGN, SETTING, AND PARTICIPANTSA multicenter randomized clinical trial was conducted in 4 outpatient clinics in Germany and Austria from January 24, 2012, to June 14, 2017, including follow-ups. Blinded measurements were conducted. A consecutive sample of 143 men was randomized to the treatment group (STICA; n = 72) or wait-list control (WLC) group (n = 71). Main inclusion criteria were male sex and internet addiction as the primary diagnosis. The STICA group had an additional 6-month follow-up (n = 36). Data were analyzed from November 2018 to March 2019. INTERVENTIONSThe manualized CBT program aimed to recover functional internet use. The program consisted of 15 weekly group and up to 8 two-week individual sessions. MAIN OUTCOMES AND MEASURESThe predefined primary outcome was the Assessment of Internet and Computer Game Addiction Self-report (AICA-S). Secondary outcomes were self-reported internet addiction symptoms, time spent online on weekdays, psychosocial functioning, and depression.RESULTS A total of 143 men (mean [SD] age, 26.2 [7.8] years) were analyzed based on intent-to-treat analyses. Of these participants, 50 of 72 men (69.4%) in the STICA group showed remission vs 17 of 71 men (23.9%) in the WLC group. In logistic regression analysis, remission in the STICA vs WLC group was higher (odds ratio, 10.10; 95% CI, 3.69-27.65), taking into account internet addiction baseline severity, comorbidity, treatment center, and age. Compared with the WLC groups, effect sizes at treatment termination of STICA were d = 1.19 for AICA-S, d = 0.88 for time spent online on weekdays, d = 0.64 for psychosocial functioning, and d = 0.67 for depression. Fourteen adverse events and 8 serious adverse events occurred. A causal relationship with treatment was considered likely in 2 AEs, one in each group.CONCLUSIONS AND RELEVANCE Short-term treatment for internet and computer game addiction is a promising, manualized, short-term CBT for a broad range of internet addictions in multiple treatment centers. Further trials investigating the long-term efficacy of STICA and addressing specific groups and subgroups compared with active control conditions are required.

Previous studies have shown that amyloid β protein (Aβ), the essential molecule for the formation of toxic oligomers and, subsequently, Alzheimer plaques, has been associated in vivo with the immune modulator, macrophage migration inhibitory factor (MIF) (17). To further investigate this association in vivo we used the APP transgenic mouse model. Serial brain sections of transgenic APP mice were stained for Aβ plaques and MIF and we observed MIF immunolabeling in microglial cells in association with Aβ plaques in the transgenic mouse brain sections. In addition, functional studies in murine and human neuronal cell lines revealed that Aβ-induced toxicity could be reversed significantly by a small molecule inhibitor of MIF (ISO-1). Finally, to elucidate the role of MIF in Alzheimer's Disease (AD) we measured MIF levels in the brain cytosol and cerebrospinal fluid (CSF) of AD patients and age-matched controls. Our results demonstrate a marked increase of MIF levels within the CSF of AD patients compared with controls. Combined, our results indicate a strong role for MIF in the pathogenesis of AD and furthermore suggest that inhibition of MIF may provide a valuable avenue of investigation for the prevention of disease onset, progression and/or severity.

Poly(trimethoxy silylpropylaniline), a nanoporous (pore diameter of 2.4 nm), electroactive (stable reversible redox characteristics), electrochromic (yellow at −0.10 V, blue green at +0.50 V, and dark green at +0.70 V), and pH‐sensitive, silica–polyaniline (PANI) hybrid material (designated as KGM‐1) has been synthesized in powder form by a simple one‐pot chemical synthesis as well as a “thin nanolayered film” by cyclic voltammetry. High‐resolution transmission image of KGM‐1 informs that the particles are spherical, with diameters in the range of 0.5–1.5 μm. X‐ray diffraction pattern of pristine KGM‐1 confirms the combined presence of ordered silica network and PANI chains. The surface area of calcined KGM‐1 is 40 m2/g (∼15 times higher than KGM‐1), and the average pore size is 2.4 nm. The N2 adsorption features also inform that PANI is present as a uniform layer within the pores of silica and because of that the silica pores are not completely blocked. The reversible redox transitions in PANI units and nanoporosity of KGM‐1 are effectively used for the electro‐driven loading/release of DNA or adenosine 5′‐triphosphate. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2010