Incorporation of Different N Sources and Light Response Curves of Nitrogenase and Photosynthesis by Cyanobacterial Blooms from Rice Fields

In this work, we estimate the contributions of the different sources of N incorporated by two N₂-fixing cyanobacterial blooms (Anabaena sp. and Microchaete sp.) in the rice fields of Valencia (Spain) during the crop cycles of 1999 and 2000, and evaluate the response of nitrogenase and C assimilation activities to changing irradiances. Our results show that, far from the generally assumed idea that the largest part of the N incorporated by N₂-fixing cyanobacterial blooms in rice fields comes from N₂ fixation, both cyanobacterial blooms incorporated about three times more N from dissolved combined compounds than from N₂ fixation (only about 33–41% of the N incorporated came from N₂ fixation). Our results on the photodependence of C and N₂ fixation indicate that in both cyanobacterial blooms, N₂ fixation showed a steeper initial slope (α) and was saturated with less irradiance than C fixation, suggesting that N₂ fixation was more efficient than photosynthesis under conditions of light limitation. At saturating light, N₂ fixation and C fixation differed depending on the bloom and on the environmental conditions created by rice plant growth. Carbon assimilation but not nitrogenase activity appeared photoinhibited in the Anabaena but not in the Microchaete bloom in August 1999, when the plants were tall and the canopy was important, and there was no limitation of dissolved inorganic carbon. The opposite was found in the Microchaete bloom of June 2000, when plants were small and produced little shade, and dissolved inorganic carbon was very low.     

Bilateral tDCS on Primary Motor Cortex: Effects on Fast Arm Reaching Tasks

BackgroundThe effects produced by transcranial direct current stimulation (tDCS) applied to the motor system have been widely studied in the past, chiefly focused on primary motor cortex (M1) excitability. However, the effects on functional tasks are less well documented.ObjectiveThis study aims to evaluate the effect of tDCS-M1 on goal-oriented actions (i.e., arm-reaching movements; ARM), in a reaction-time protocol.Methods13 healthy subjects executed dominant ARM as fast as possible to one of two targets in front of them while surface EMG was recorded. Participants performed three different sessions. In each session they first executed ARM (Pre), then received tDCS, and finally executed Post, similar to Pre. Subjects received three different types of tDCS, one per session: In one session the anode was on right-M1 (AR), and the cathode on the left-M1 (CL), thus termed AR-CL; AL-CR reversed the montage; and Sham session was applied likewise. Real stimulation was 1mA-10min while subjects at rest. Three different variables and their coefficients of variation (CV) were analyzed: Premotor times (PMT), reaction-times (RT) and movement-times (MT).Resultstriceps-PMT were significantly increased at Post-Sham, suggesting fatigue. Results obtained with real tDCS were not different depending on the montage used, in both cases PMT were significantly reduced in all recorded muscles. RT and MT did not change for real or sham stimulation. RT-CV and PMT-CV were reduced after all stimulation protocols.ConclusiontDCS reduces premotor time and fatigability during the execution of fast motor tasks. Possible underlying mechanisms are discussed.     

CIGB-300, a novel proapoptotic peptide that impairs the CK2 phosphorylation and exhibits anticancer properties both in vitro and in vivo

Protein Kinase CK2 is a serine-threonine kinase frequently deregulated in many human tumors. Here, we hypothesized that a peptide binder to the CK2 phosphoacceptor site could exhibit anticancer properties in vitro, in tumor animal models, and in cancer patients. By screening a random cyclic peptide phage display library, we identified the CIGB-300 (formerly P15-Tat), a cyclic peptide which abrogates the CK2 phosphorylation by blocking recombinant substrates in vitro. Interestingly, synthetic CIGB-300 led to a dose-dependent antiproliferative effect in a variety of tumor cell lines and induced apoptosis as evidenced by rapid caspase activation. Importantly, CIGB-300 elicited significant antitumor effect both by local and systemic administration in murine syngenic tumors and human tumors xenografted in nude mice. Finally, we performed a First-in-Man trial with CIGB 300 in patients with cervical malignancies. The peptide was found to be safe and well tolerated in the dose range studied. Likewise, signs of clinical benefit were clearly identified after the CIGB-300 treatment as evidenced by significant decrease of the tumor lesion area and histological examination. Our results provide an early proof-of-principle of clinical benefit by using an anti-CK2 approach in cancer. Furthermore, this is the first clinical trial where an investigational drug has been used to target the CK2 phosphorylation domain.     

Limnological characteristics of the freshwater ecosystems of Byers Peninsula, Livingston Island, in maritime Antarctica

A limnological survey of 15 lakes and 6 streams was carried out on Byers Peninsula (Livingston Island, South Shetland Islands, Antarctica) during austral summer 2001–2002. Most of the surface waters had low conductivities (20–105 μS cm⁻¹) and nutrients (total phosphorus 0.01–0.24 μM), but some coastal lakes were enriched by nutrient inputs from seal colonies and marine inputs. Plankton communities in the lakes contained picocyanobacteria (10²–10⁴ cells ml⁻¹), diatoms, chrysophytes and chlorophytes, and a large fraction of the total biomass was bacterioplankton. Zooplankton communities were dominated by Boeckella poppei and Branchinecta gainii; the benthic cladoceran Macrothrix ciliata was also recorded, for the first time in Antarctica. The chironomids Belgica antarctica and Parochlus steinenii, and the oligochaete Lumbricillus sp., occurred in stream and lake benthos. The phytobenthos included cyanobacterial mats, epilithic diatoms and the aquatic moss Drepanocladus longifolius. These observations underscore the limnological richness of this seasonally ice-free region in maritime Antarctica and its value as a long-term reference site for monitoring environmental change.     

Defining priorities for improving end-of-life care in Canada

Background

High-quality end-of-life care should be the right of every Canadian. The objective of this study was to identify aspects of end-of-life care that are high in priority as targets for improvement using feedback elicited from patients and their families.

Methods

We conducted a multicentre, cross-sectional survey involving patients with advanced, life-limiting illnesses and their family caregivers. We administered the Canadian Health Care Evaluation Project (CANHELP) questionnaire along with a global rating question to measure satisfaction with end-of-life care. We derived the relative importance of individual questions on the CANHELP questionnaire from their association with a global rating of satisfaction, as determined using Pearson correlation coefficients. To determine high-priority issues, we identified questions that had scores indicating high importance and low satisfaction.

Results

We approached 471 patients and 255 family members, of whom 363 patients and 193 family members participated, with response rates of 77% for patients and 76% for families. From the perspective of patients, high-priority areas needing improvement were related to feelings of peace, to assessment and treatment of emotional problems, to physician availability and to satisfaction that the physician took a personal interest in them, communicated clearly and consistently, and listened. From the perspective of family members, similar areas were identified as high in priority, along with the additional areas of timely information about the patient’s condition and discussions with the doctor about final location of care and use of end-of-life technology.

Interpretation

End-of-life care in Canada may be improved for patients and their families by providing better psychological and spiritual support, better planning of care and enhanced relationships with physicians, especially in aspects related to communication and decision-making.Although a “quality death” is an espoused right of Canadians,¹ for many dying patients and their families, it is not achieved. Recent reviews and observational studies describe considerable dissatisfaction with end-of-life care, indicating that there are still opportunities for improvement.^2–5Ideally, initiatives aimed at improving end-of-life care would be informed by the experiences and expectations of patients and their family members. However, such efforts are often hampered by inadequate definitions of quality of care and by suboptimal tools for measurement.^6–8 In a recent, large cross-sectional survey, the Canadian Researchers at the End of Life Network defined what matters most to seriously ill patients as they approach the end of life.⁹ Both patients and their family members reported that it was extremely important that they have trust and confidence in the physicians caring for them or their loved ones.⁹ Avoidance of unwanted life-support measures, effective communication, continuity of care, and feelings of life completion were also rated as highly important.⁹ We used these comprehensive ratings of importance to develop and validate a novel questionnaire to measure satisfaction with end-of-life care.¹⁰ Using this questionnaire, we formally evaluated the care received at the end of life in several Canadian centres.By targeting initiatives for change at gaps in quality, we can address the highest priorities for improving end-of-life care in Canada. Our objective was to identify high-priority areas for improvement in the care of patients with advanced, life-limiting diseases and in the perceived quality of that care by their families. We identified these areas by focusing on care-related issues that had been rated as important by patients and their family members but were rated low on the questionnaire measuring satisfaction with end-of-life care.     

Understanding the disrupting mechanism of the Tau aggregation motif “306VQIVYK311” by phenylthiazolyl‐hydrazides inhibitors

Alzheimer's disease is a progressive neurodegenerative disorder characterized by the abnormal processing of the Tau and the amyloid precursor proteins. The unusual aggregation of Tau is based on the formation of intermolecular β‐sheets through two motifs: ²⁷⁵VQIINK²⁸⁰ and ³⁰⁶VQIVYK³¹¹. Phenylthiazolyl‐hydrazides (PTHs) are capable of inhibiting/disassembling Tau aggregates. However, the disaggregation mechanism of Tau oligomers by PTHs is still unknown. In this work, we studied the disruption of the oligomeric form of the Tau motif ³⁰⁶VQIVYK³¹¹ by PTHs through molecular docking, molecular dynamics, and free energy calculations. We predicted hydrophobic interactions as the major driving forces for the stabilization of Tau oligomer, with V306 and I308 being the major contributors. Nonpolar component of the binding free energy is essential to stabilize Tau‐PTH complexes. PTHs disrupted mainly the van der Waals interactions between the monomers, leading to oligomer destabilization. Destabilization of full Tau filament by PTHs and emodin was not observed in the sampled 20 ns; however, in all cases, the nonpolar component of the binding free energy is essential for the formation of Tau filament‐PTH and Tau filament‐emodin. These results provide useful clues for the design of more effective Tau‐aggregation inhibitors.