Plasma normetanephrine: A biochemical marker of sympathetic nerve function in man

The concentration of the catecholamines in plasma are regarded by many investigators as biochemical markers of sympathoadrenal activity in man. This study was designed to: 1) assess the relationship of normetanephrine (NMN), the metabolite of norepinephrine (NE) most likely to represent degration of newly synthesized and released “active” norepinephrine, to that of norepinephrine in plasma of normal volunteers and 2) to determine regional variations in plasma normetanephrine concentrations at venous and arterial sites of patients undergoing cardiac catherization. The findings suggest that 1) plasma normetanephrine reflects sympathoadrenal activity and neurotransmitter production at both peripheral neuronal and adrenal medullary sites and 2) there is net removal of normetanephrine by liver and kidney. Plasma normetanephrine should provide assistance in the biochemical assessment of sympathoadrenal tone in man and in patients with various autonomic disorders.     

Synthetic model peptides phosphorylated in vitro by NII kinase and cation-mediated interactions with DNA

Minimum substrate requirements for nuclear NII kinase (casein II kinase) were analyzed with synthetic peptides modeled according to amino acid composition of phosphopeptides isolated from chromatin. Uncharged blocked peptide termini decreased the requirement for acidic clusters neighboring the phosphate acceptor amino acid (serine) such that only one group immediately N-terminal to serine was sufficient for kinase activity. Studies on peptide interaction with DNA showed that the model phosphopeptides bound to DNA only in the phosphorylated form suggesting involvement of phosphorylation in protein-DNA interactions yet to be identified.     

The prognostic value of CD3+ tumor-infiltrating lymphocytes for stage II colon cancer according to use of adjuvant chemotherapy: A large single-institution cohort study

BackgroundHigh tumor infiltrating lymphocytes (TILs) density was previously shown to be associated with favorable prognosis for patients with colon cancer (CC). However, the impact of TILs on overall survival (OS) of stage II CC patients who received adjuvant chemotherapy (ADJ) or not (no-ADJ) is unknown. We assessed the prognostic value of CD3+ TILs in stage II CC patients according to whether they had ADJ or not.MethodsPatients treated with curative surgery for stage II CC (2002–2013) were selected from the Santa Maria alle Scotte Hospital registry. TILs at the invasive front, center of tumor, and stroma were determined by immunohistochemistry and manually quantified as the rate of TILs/total tissue areas. High TILs (H-TILs) was defined as >20%. Patients were categorized as high or low TILs (L-TILs) and ADJ or no-ADJ.ResultsOf the 678 patients included, 137 (20%) received ADJ and 541 (80%) did not. The distribution of the 4 groups were: 16% (L-TIL/ADJ), 64% (L-TIL/no-ADJ), 5% (H-TIL/ADJ), 15% (H-TIL/no-ADJ). Compared to H-TILs/no-ADJ, ADJ patients showed a significantly increased OS (P<.01) regardless of the TILs rate whereas L-TILs/no-ADJ had significantly decreased OS and higher risk of death (HR=1.41; 95% CI, 1.06–1.88; P<.0001). On multivariable analysis, the unfavorable prognostic value of L-TILs (vs. H-TILs) for no-ADJ patients was confirmed (HR=1.36; 95% CI 1.02, 1.82; P=.0373).ConclusionLow CD3+ TILs rate was associated with shorter OS in those with stage II colon cancer who did not receive adjuvant therapy. Low CD3+ TILs could be considered an additional risk factor for still ADJ-untreated stage II CC patients, which could facilitate clinical decision making.     

The VIRCA Project: virus resistant cassava for Africa

The VIRCA (Virus Resistant Cassava for Africa) project is a collaborative program between the Donald Danforth Plant Science Center, USA the National Crops Resources Research Institute, Uganda and the Kenya Agricultural Research Institute, Kenya. VIRCA is structured to include all aspects of the intellectual property, technology, regulatory, biosafety, quality control, communication and distribution components required for a GM crop development and delivery process. VIRCA's goal is to improve cassava for resistance to the viral diseases cassava brown streak disease (CBSD) and cassava mosaic disease (CMD) using pathogen-derived RNAi technology, and to field test, obtain regulatory approval for and deliver these products to small landholder farmers. During Phase I of the project, proof of concept was achieved by production and testing of virus resistant plants under greenhouse and confined field trials in East Africa. In VIRCA Phase II, two farmer-preferred varieties will be modified for resistance to CBSD and CMD, and lead events identified after molecular and field screening. In addition to delivery of royalty-free improved planting materials for farmers, VIRCA capacity building activities are enhancing indigenous capability for crop biotechnology in East Africa.