Cdk5 Phosphorylates Dopamine D2 Receptor and Attenuates Downstream Signaling

The dopamine D2 receptor (DRD2) is a key receptor that mediates dopamine-associated brain functions such as mood, reward, and emotion. Cyclin-dependent kinase 5 (Cdk5) is a proline-directed serine/threonine kinase whose function has been implicated in the brain reward circuit. In this study, we revealed that the serine 321 residue (S321) in the third intracellular loop of DRD2 (D2i3) is a novel regulatory site of Cdk5. Cdk5-dependent phosphorylation of S321 in the D2i3 was observed in in vitro and cell culture systems. We further observed that the phosphorylation of S321 impaired the agonist-stimulated surface expression of DRD2 and decreased G protein coupling to DRD2. Moreover, the downstream cAMP pathway was affected in the heterologous system and in primary neuronal cultures from p35 knockout embryos likely due to the reduced inhibitory activity of DRD2. These results indicate that Cdk5-mediated phosphorylation of S321 inhibits DRD2 function, providing a novel regulatory mechanism for dopamine signaling.X111111sciescopu

Is lymphovascular invasion a powerful predictor for biochemical recurrence in pT3 N0 prostate cancer?: Results from the K-CaP database

To assess the impact of lymphovascular invasion (LVI) on the risk of biochemical recurrence (BCR) in pT3 N0 prostate cancer, clinical data were extracted from 1,622 patients with pT3 N0 prostate cancer from the K-CaP database. Patients with neoadjuvant androgen deprivation therapy (n = 325) or insufficient pathologic or follow-up data (n = 87) were excluded. The primary endpoint was the oncologic importance of LVI, and the secondary endpoint was the hierarchical relationships for estimating BCR between the evaluated variables. LVI was noted in 260 patients (21.5%) and was significantly associated with other adverse clinicopathologic features. In the multivariate Cox regression analysis, LVI was significantly associated with an increased risk of BCR after adjusting for known prognostic factors. In the Bayesian belief network analysis, LVI and pathologic Gleason score were found to be first-degree associates of BCR, whereas prostate-specific antigen (PSA) level, seminal vesicle invasion, perineural invasion, and high-grade prostatic intraepithelial neoplasia were considered second-degree associates. In the random survival forest, pathologic Gleason score, LVI, and PSA level were three most important variables in determining BCR of patients with pT3 N0 prostate cancer. In conclusion, LVI is one of the most powerful adverse prognostic factors for BCR in patients with pT3 N0 prostate cancer.1132Ysciescopu

Quality improvement in ammonium nitrate production using Six Sigma methodology

Six sigma has been used in different industries to reach operational excellence. However, in the chemical industry, the application of this methodology is limited. This research presents an implementation of the six sigma method for ammonium nitrate (AN) content optimization in condensate production for a fertilizer company in Colombia. The paper aims to determine the levels for input variables in the process, to meet desirable standards for condensate quality in terms of ammonium nitrate content. Based on the DMAIC steps implementation, it was possible to establish the main variables affecting the condensate quality and their optimal levels to reach an ammonium nitrate content below 15,000 ppm. These results demonstrate the impact that a six sigma project may have on operational effectiveness and quality improvement for meeting the customer requirements

Positional Signaling and Expression of ENHANCER OF TRY AND CPC1 Are Tuned to Increase Root Hair Density in Response Phosphate Deficiency in Arabidopsis thaliana

Phosphate (Pi) deficiency induces a multitude of responses aimed at improving the acquisition of Pi, including an increased density of root hairs. To understand the mechanisms involved in Pi deficiency-induced alterations of the root hair phenotype in Arabidopsis (Arabidopsis thaliana), we analyzed the patterning and length of root epidermal cells under control and Pi-deficient conditions in wild-type plants and in four mutants defective in the expression of master regulators of cell fate, CAPRICE (CPC), ENHANCER OF TRY AND CPC 1 (ETC1), WEREWOLF (WER) and SCRAMBLED (SCM). From this analysis we deduced that the longitudinal cell length of root epidermal cells is dependent on the correct perception of a positional signal (‘cortical bias’) in both control and Pi-deficient plants; mutants defective in the receptor of the signal, SCM, produced short cells characteristic of root hair-forming cells (trichoblasts). Simulating the effect of cortical bias on the time-evolving probability of cell fate supports a scenario in which a compromised positional signal delays the time point at which non-hair cells opt out the default trichoblast pathway, resulting in short, trichoblast-like non-hair cells. Collectively, our data show that Pi-deficient plants increase root hair density by the formation of shorter cells, resulting in a higher frequency of hairs per unit root length, and additional trichoblast cell fate assignment via increased expression of ETC1

Thermally stable single atom Pt/m-Al2O3 for selective hydrogenation and CO oxidation

Single-atom metal catalysts offer a promising way to utilize precious noble metal elements more effectively, provided that they are catalytically active and sufficiently stable. Herein, we report a synthetic strategy for Pt single-atom catalysts with outstanding stability in several reactions under demanding conditions. The Pt atoms are firmly anchored in the internal surface of mesoporous Al2O3, likely stabilized by coordinatively unsaturated pentahedral Al3+ centres. The catalyst keeps its structural integrity and excellent performance for the selective hydrogenation of 1,3-butadiene after exposure to a reductive atmosphere at 200 °C for 24 h. Compared to commercial Pt nanoparticle catalyst on Al2O3 and control samples, this system exhibits significantly enhanced stability and performance for n-hexane hydro-reforming at 550 °C for 48 h, although agglomeration of Pt single-atoms into clusters is observed after reaction. In CO oxidation, the Pt single-atom identity was fully maintained after 60 cycles between 100 and 400 °C over a one-month period

Multicenter retrospective analysis of 581 patients with primary intestinal non-hodgkin lymphoma from the Consortium for Improving Survival of Lymphoma (CISL)

<p>Abstract</p> <p>Background</p> <p>Primary intestinal non-Hodgkin lymphoma (NHL) is a heterogeneous disease with regard to anatomic and histologic distribution. Thus, analyses focusing on primary intestinal NHL with large number of patients are warranted.</p> <p>Methods</p> <p>We retrospectively analyzed 581 patients from 16 hospitals in Korea for primary intestinal NHL in this retrospective analysis. We compared clinical features and treatment outcomes according to the anatomic site of involvement and histologic subtypes.</p> <p>Results</p> <p>B-cell lymphoma (n = 504, 86.7%) was more frequent than T-cell lymphoma (n = 77, 13.3%). Diffuse large B-cell lymphoma (DLBCL) was the most common subtype (n = 386, 66.4%), and extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) was the second most common subtype (n = 61, 10.5%). B-cell lymphoma mainly presented as localized disease (Lugano stage I/II) while T-cell lymphomas involved multiple intestinal sites. Thus, T-cell lymphoma had more unfavourable characteristics such as advanced stage at diagnosis, and the 5-year overall survival (OS) rate was significantly lower than B-cell lymphoma (28% versus 71%, P < 0.001). B symptoms were relatively uncommon (20.7%), and bone marrow invasion was a rare event (7.4%). The ileocecal region was the most commonly involved site (39.8%), followed by the small (27.9%) and large intestines (21.5%). Patients underwent surgery showed better OS than patients did not (5-year OS rate 77% versus 57%, P < 0.001). However, this beneficial effect of surgery was only statistically significant in patients with B-cell lymphomas (P < 0.001) not in T-cell lymphomas (P = 0.460). The comparison of survival based on the anatomic site of involvement showed that ileocecal regions had a better 5-year overall survival rate (72%) than other sites in consistent with that ileocecal region had higher proportion of patients with DLBCL who underwent surgery. Age > 60 years, performance status ≥ 2, elevated serum lactate dehydrogenase, Lugano stage IV, presence of B symptoms, and T-cell phenotype were independent prognostic factors for survival.</p> <p>Conclusions</p> <p>The survival of patients with ileocecal region involvement was better than that of patients with involvement at other sites, which might be related to histologic distribution, the proportion of tumor stage, and need for surgical resection.</p

Characterization and genomic analysis of chromate resistant and reducing Bacillus cereus strain SJ1

<p>Abstract</p> <p>Background</p> <p>Chromium is a toxic heavy metal, which primarily exists in two inorganic forms, Cr(VI) and Cr(III). Chromate [Cr(VI)] is carcinogenic, mutational, and teratogenic due to its strong oxidizing nature. Biotransformation of Cr(VI) to less-toxic Cr(III) by chromate-resistant and reducing bacteria has offered an ecological and economical option for chromate detoxification and bioremediation. However, knowledge of the genetic determinants for chromate resistance and reduction has been limited so far. Our main aim was to investigate chromate resistance and reduction by <it>Bacillus cereus </it>SJ1, and to further study the underlying mechanisms at the molecular level using the obtained genome sequence.</p> <p>Results</p> <p><it>Bacillus cereus </it>SJ1 isolated from chromium-contaminated wastewater of a metal electroplating factory displayed high Cr(VI) resistance with a minimal inhibitory concentration (MIC) of 30 mM when induced with Cr(VI). A complete bacterial reduction of 1 mM Cr(VI) was achieved within 57 h. By genome sequence analysis, a putative chromate transport operon, <it>chrIA</it>1, and two additional <it>chrA </it>genes encoding putative chromate transporters that likely confer chromate resistance were identified. Furthermore, we also found an azoreductase gene <it>azoR </it>and four nitroreductase genes <it>nitR </it>possibly involved in chromate reduction. Using reverse transcription PCR (RT-PCR) technology, it was shown that expression of adjacent genes <it>chrA</it>1 and <it>chrI </it>was induced in response to Cr(VI) but expression of the other two chromate transporter genes <it>chrA</it>2 and <it>chrA</it>3 was constitutive. In contrast, chromate reduction was constitutive in both phenotypic and gene expression analyses. The presence of a resolvase gene upstream of <it>chrIA</it>1, an arsenic resistance operon and a gene encoding Tn7-like transposition proteins ABBCCCD downstream of <it>chrIA</it>1 in <it>B. cereus </it>SJ1 implied the possibility of recent horizontal gene transfer.</p> <p>Conclusion</p> <p>Our results indicate that expression of the chromate transporter gene <it>chrA</it>1 was inducible by Cr(VI) and most likely regulated by the putative transcriptional regulator ChrI. The bacterial Cr(VI)-resistant level was also inducible. The presence of an adjacent arsenic resistance gene cluster nearby the <it>chrIA</it>1 suggested that strong selective pressure by chromium and arsenic could cause bacterial horizontal gene transfer. Such events may favor the survival and increase the resistance level of <it>B. cereus </it>SJ1.</p

Reduction of hexavalent chromium by Ochrobactrum intermedium BCR400 isolated from a chromium-contaminated soil

Hexavalent chromium-resistant Ochrobactrum intermedium BCR400 was isolated from chromium contaminated soil collected from Vadodara, Gujarat. It reduced 100 mg Cr(VI)/L completely in 52 h with initial Cr(VI) reduction rate of 1.98 mg/L/h. The Cr(VI) reduction rate decreased with increase in Cr(VI) concentration from 100 to 500 mg/L. The addition of anthraquinone-2-sulphonic acid (AQS) to culture O. intermedium BCR400 significantly enhanced its chromium reduction rate. The activation energy of AQS-mediated Cr(VI) reduction (120.69 KJ/mol) was 1.1-fold lower than non-mediated Cr(VI) reduction. An increase in the activities of quinone reductase and chromate reductase in cells grown in presence of AQS/AQS + Cr(VI) suggests their role in reduction of Cr(VI) by O. intermedium. Both chromate reductase and quinone reductase activities were FAD independent, required NADH as reductant, displayed maximum activity at pH (7.0) and temperature (30 °C). Thus Cr(VI) bioremediation potential of O. intermedium can be enhanced by augmentation of system with AQS as redox mediator