Salvage Cryotherapy for Radiation-Recurrent Prostate Cancer: Outcomes and Complications

Potentially curative salvage options for radio-recurrent prostate cancer include prostatectomy, brachytherapy, high-intensity focused ultrasound, and cryotherapy. Salvage cryoablation technology, surgical technique, oncologic outcomes, and complication rates have improved dramatically over the past few decades, shifting this treatment modality from investigational status to an established therapeutic option. In this review, we focus on the most up-to-date oncologic and functional outcomes, as well as complications of salvage cryotherapy for radiation-recurrent prostate cancer

The Economic Archaeology of Roman Economic Performance

Recent years have witnessed a paradigm shift in the study of the Roman economy. Methodologically modern economic analysis is now far more acceptable than it once was, and archaeology has become the major source of empirical data for many questions. On the substantive side there is now a far clearer appreciation of the major changes that the Roman economy underwent, with substantial growth of population and aggregate production and even some improvements in standard of living, but followed by equally dramatic decline. This economic success was not limited to the imperial core, but also extended to the provinces

Reduction of Dopamine Level Enhances the Attractiveness of Male Drosophila to Other Males

Dopamine is an important neuromodulator in animals and its roles in mammalian sexual behavior are extensively studied. Drosophila as a useful model system is widely used in many fields of biological studies. It has been reported that dopamine reduction can affect female receptivity in Drosophila and leave male-female courtship behavior unaffected. Here, we used genetic and pharmacological approaches to decrease the dopamine level in dopaminergic cells in Drosophila, and investigated the consequence of this manipulation on male homosexual courtship behavior. We find that reduction of dopamine level can induce Drosophila male-male courtship behavior, and that this behavior is mainly due to the increased male attractiveness or decreased aversiveness towards other males, but not to their enhanced propensity to court other males. Chemical signal input probably plays a crucial role in the male-male courtship induced by the courtees with reduction of dopamine. Our finding provides insight into the relationship between the dopamine reduction and male-male courtship behavior, and hints dopamine level is important for controlling Drosophila courtship behavior

Study of the reaction e^{+}e^{-} -->J/psi\pi^{+}\pi^{-} via initial-state radiation at BaBar

We study the process $e^+e^-\to J/\psi\pi^{+}\pi^{-}$ with initial-state-radiation events produced at the PEP-II asymmetric-energy collider. The data were recorded with the BaBar detector at center-of-mass energies 10.58 and 10.54 GeV, and correspond to an integrated luminosity of 454 $\mathrm{fb^{-1}}$. We investigate the $J/\psi \pi^{+}\pi^{-}$ mass distribution in the region from 3.5 to 5.5 $\mathrm{GeV/c^{2}}$. Below 3.7 $\mathrm{GeV/c^{2}}$ the $\psi(2S)$ signal dominates, and above 4 $\mathrm{GeV/c^{2}}$ there is a significant peak due to the Y(4260). A fit to the data in the range 3.74 -- 5.50 $\mathrm{GeV/c^{2}}$ yields a mass value $4244 \pm 5$ (stat) $\pm 4$ (syst)$\mathrm{MeV/c^{2}}$ and a width value $114 ^{+16}_{-15}$ (stat)$\pm 7$(syst)$\mathrm{MeV}$ for this state. We do not confirm the report from the Belle collaboration of a broad structure at 4.01 $\mathrm{GeV/c^{2}}$. In addition, we investigate the $\pi^{+}\pi^{-}$ system which results from Y(4260) decay

Beneficial immune modulatory effects of a specific nutritional combination in a murine model for cancer cachexia

The majority of patients with advanced cancer are recognised by impaired immune competence influenced by several factors, including the type and stage of the tumour and the presence of cachexia. Recently, a specific nutritional combination containing fish oil, specific oligosaccharide mixture, high protein content and leucine has been developed aimed to support the immune system of cancer patients in order to reduce the frequency and severity of (infectious) complications. In a recently modified animal model cachexia is induced by inoculation of C26 tumour cells in mice. In a pre-cachectic state, no effect was observed on contact hypersensitivity, a validated in vivo method to measure Th1-mediated immune function, after adding the individual nutritional ingredients to the diet of tumour-bearing mice. However, the complete mixture resulted in significantly improved Th1 immunity. Moreover, in a cachectic state, the complete mixture reduced plasma levels of pro-inflammatory cytokines and beneficially affected ex vivo immune function. Accordingly, the combination of the nutritional ingredients is required to obtain a synergistic effect, leading to a reduced inflammatory state and improved immune competence. From this, it can be concluded that the specific nutritional combination has potential as immune-supporting nutritional intervention to reduce the risk of (infectious) complications in cancer patients

Eukaryotic Cells Producing Ribosomes Deficient in Rpl1 Are Hypersensitive to Defects in the Ubiquitin-Proteasome System

It has recently become clear that the misassembly of ribosomes in eukaryotic cells can have deleterious effects that go far beyond a simple shortage of ribosomes. In this work we find that cells deficient in ribosomal protein L1 (Rpl1; Rpl10a in mammals) produce ribosomes lacking Rpl1 that are exported to the cytoplasm and that can be incorporated into polyribosomes. The presence of such defective ribosomes leads to slow growth and appears to render the cells hypersensitive to lesions in the ubiquitin-proteasome system. Several genes that were reasonable candidates for degradation of 60S subunits lacking Rpl1 fail to do so, suggesting that key players in the surveillance of ribosomal subunits remain to be found. Interestingly, in spite of rendering the cells hypersensitive to the proteasome inhibitor MG132, shortage of Rpl1 partially suppresses the stress-invoked temporary repression of ribosome synthesis caused by MG132.United States. National Institutes of Health (GM25532)United States. National Institutes of Health (ARRAGM25532-S1)United States. National Institutes of Health (GM085177)United States. National Institutes of Health (CAI-3330)Natural Sciences and Engineering Research Council of Canada (NSERC

Specificity of DNA-binding by the FAX-1 and NHR-67 nuclear receptors of Caenorhabditis elegans is partially mediated via a subclass-specific P-box residue

<p>Abstract</p> <p>Background</p> <p>The nuclear receptors of the NR2E class play important roles in pattern formation and nervous system development. Based on a phylogenetic analysis of DNA-binding domains, we define two conserved groups of orthologous NR2E genes: the NR2E1 subclass, which includes <it>C. elegans nhr-67, Drosophila tailless </it>and <it>dissatisfaction</it>, and vertebrate Tlx (NR2E2, NR2E4, NR2E1), and the NR2E3 subclass, which includes <it>C. elegans fax-1 </it>and vertebrate PNR (NR2E5, NR2E3). PNR and Tll nuclear receptors have been shown to bind the hexamer half-site AAGTCA, instead of the hexamer AGGTCA recognized by most other nuclear receptors, suggesting unique DNA-binding properties for NR2E class members.</p> <p>Results</p> <p>We show that NR2E3 subclass member FAX-1, unlike NHR-67 and other NR2E1 subclass members, binds to hexamer half-sites with relaxed specificity: it will bind hexamers with the sequence ANGTCA, although it prefers a purine to a pyrimidine at the second position. We use site-directed mutagenesis to demonstrate that the difference between FAX-1 and NHR-67 binding preference is partially mediated by a conserved subclass-specific asparagine or aspartate residue at position 19 of the DNA-binding domain. This amino acid position is part of the "P box" that plays a critical role in defining binding site specificity and has been shown to make hydrogen-bond contacts to the second position of the hexamer in co-crystal structures for other nuclear receptors. The relaxed specificity allows FAX-1 to bind a much larger repertoire of half-sites than NHR-67. While NR2E1 class proteins bind both monomeric and dimeric sites, the NR2E3 class proteins bind only dimeric sites. The presence of a single strong site adjacent to a very weak site allows dimeric FAX-1 binding, further increasing the number of dimeric binding sites to which FAX-1 may bind <it>in vivo</it>.</p> <p>Conclusion</p> <p>These findings identify subclass-specific DNA-binding specificities and dimerization properties for the NR2E1 and NR2E3 subclasses. For the NR2E1 protein NHR-67, Asp-19 permits binding to AAGTCA half-sites, while Asn-19 permits binding to AGGTCA half-sites. The apparent conservation of DNA-binding properties between vertebrate and nematode NR2E receptors allows for the possibility of evolutionarily-conserved regulatory patterns.</p