Physical Activity Characteristics across GOLD Quadrants Depend on the Questionnaire Used

Background

The GOLD multidimensional classification of COPD severity combines the exacerbation risk with the symptom experience, for which 3 different questionnaires are permitted. This study investigated differences in physical activity (PA) in the different GOLD quadrants and patient’s distribution in relation to the questionnaire used.

Methods

136 COPD patients (58±21% FEV₁ predicted, 34F/102M) completed COPD assessment test (CAT), clinical COPD questionnaire (CCQ) and modified Medical Research Council (mMRC) questionnaire. Exacerbation history, spirometry and 6MWD were collected. PA was objectively measured for 2 periods of 1 week, 6 months apart, in 5 European centres; to minimise seasonal and clinical variation the average of these two periods was used for analysis.

Results

GOLD quadrants C+D had reduced PA compared with A+B (3824 [2976] vs. 5508 [4671] steps.d-1, p<0.0001). The choice of questionnaire yielded different patient distributions (agreement mMRC-CAT κ = 0.57; CCQ-mMRC κ = 0.71; CCQ-CAT κ = 0.72) with different clinical characteristics. PA was notably lower in patients with an mMRC score ≥2 (3430 [2537] vs. 5443 [3776] steps.d^-1, p <0.001) in both the low and high risk quadrants.

Conclusions

Using different questionnaires changes the patient distribution and results in different clinical characteristics. Therefore, standardization of the questionnaire used for classification is critical to allow comparison of different studies using this as an entry criterion.

Clinical Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01388218","term_id":"NCT01388218"}}NCT01388218     

Recovery of Dynamics and Function in Spiking Neural Networks with Closed-Loop Control

There is a growing interest in developing novel brain stimulation methods to control disease-related aberrant neural activity and to address basic neuroscience questions. Conventional methods for manipulating brain activity rely on open-loop approaches that usually lead to excessive stimulation and, crucially, do not restore the original computations performed by the network. Thus, they are often accompanied by undesired side-effects. Here, we introduce delayed feedback control (DFC), a conceptually simple but effective method, to control pathological oscillations in spiking neural networks (SNNs). Using mathematical analysis and numerical simulations we show that DFC can restore a wide range of aberrant network dynamics either by suppressing or enhancing synchronous irregular activity. Importantly, DFC, besides steering the system back to a healthy state, also recovers the computations performed by the underlying network. Finally, using our theory we identify the role of single neuron and synapse properties in determining the stability of the closed-loop system.     

A novel arrangement of zinc finger nuclease system for in vivo targeted genome engineering: the tomato <Emphasis Type="Italic">LEC1</Emphasis>-<Emphasis Type="Italic">LIKE4</Emphasis> gene case

Key message

A selection-free, highly efficient targeted mutagenesis approach based on a novel ZFN monomer arrangement for genome engineering in tomato reveals plant trait modifications.

Abstract

How to achieve precise gene targeting in plants and especially in crops remains a long-sought goal for elucidating gene function and advancing molecular breeding. To address this issue, zinc finger nuclease (ZFN)-based technology was developed for the Solanum lycopersicum seed system. A ZFN architecture design with an intronic sequence between the two DNA recognition sites was evaluated for its efficiency in targeted gene mutagenesis. Custom engineered ZFNs for the developmental regulator LEAFY-COTYLEDON1-LIKE4 (L1L4) coding for the β subunit of nuclear factor Y, when transiently expressed in tomato seeds, cleaved the target site and stimulated imperfect repair driven by nonhomologous end-joining, thus, introducing mutations into the endogenous target site. The successful in planta application of the ZFN platform resulted in L1L4 mutations which conferred heterochronic phenotypes during development. Our results revealed that sequence changes upstream of the DNA binding domain of L1L4 can lead to phenotypic diversity including fruit organ. These results underscore the utility of engineered ZFN approach in targeted mutagenesis of tomato plant which may accelerate translational research and tomato breeding.

     

Microtubules as mechanical force sensors

Microtubules are polymers of tubulin subunits (dimers) arranged on a hexagonal lattice. Each tubulin dimer comprises two monomers, the alpha-tubulin and beta-tubulin, and can be found in two states. In the first state a mobile negative charge is located into the alpha-tubulin monomer and in the second into the beta-tubulin monomer. Each tubulin dimer is modeled as an electrical dipole coupled to its neighbors by electrostatic forces. The location of the mobile charge in each dimer depends on the location of the charges in the dimer's neighborhood. Mechanical forces that act on the microtubule affect the distances between the dimers and alter the electrostatic potential. Changes in this potential affect the mobile negative charge location in each dimer and the charge distribution in the microtubule. The net effect is that mechanical forces affect the charge distribution in microtubules. We propose to exploit this effect and use microtubules as mechanical force sensors. We model each dimer as a two-state quantum system and, following the quantum computation paradigm, we use discrete quantum random walk on the hexagonal microtubule lattice to determine the charge distribution. Different forces applied on the microtubule are modeled as different coin biases leading to different probability distributions of the quantum walker location, which are directly connected to different charge distributions. Simulation results show that there is a strong indication that microtubules can be used as mechanical force sensors and that they can also detect the force directions and magnitudes.     

Benthic foraminiferal assemblages in the severely polluted coastal environment of Drapetsona-Keratsini,Saronikos Gulf (Greece)

Surface sediments were collected from the coastal zone of Drapetsona–Keratsini (Saronikos Gulf, Greece) in December 2012 for determining the local benthic foraminiferal community, identifying their spatial distribution patterns, and evaluating the response of foraminiferal species to geochemical composition through the hierarchical cluster analysis, principal component analysis and Spearman's rho correlation. Foraminifera can be classified into three distinct assemblages associated with the granulometry, elemental geochemistry, particulate organic carbon content and degree of sediment contamination. A relatively low-diversity assemblage, dominated by stress-tolerant taxa with Ammonia tepida Bolivina spathulata and Bulimina elongata being the prevailing species, is characteristic of the silty seabed of the main part of Drapetsona coastal zone and the Keratsini Port central basin, where organic carbon content, aliphatic and polycyclic aromatic hydrocarbons concentrations and trace metal loads are greatly elevated. On the sandy bottom of the investigated area, relatively high frequencies of miliolids prevail. An epiphytic rotaliid-dominated assemblage is recorded in the slightly-polluted sedimentary bottom of the inner and western part of the Keratsini Port.     

Functional analysis of LHCSR1, a protein catalyzing NPQ in mosses,by heterologous expression in Arabidopsis thaliana

Photosynthesis Research - Non-photochemical quenching, NPQ, of chlorophyll fluorescence regulates the heat dissipation of chlorophyll excited states and determines the efficiency of the oxygenic...     

Improving physical activity in COPD: towards a new paradigm

Chronic obstructive pulmonary disease (COPD) is a debilitating disease affecting patients in daily life, both physically and emotionally. Symptoms such as dyspnea and muscle fatigue, lead to exercise intolerance, which, together with behavioral issues, trigger physical inactivity, a key feature of COPD. Physical inactivity is associated with adverse clinical outcomes, including hospitalization and all-cause mortality. Increasing activity levels is crucial for effective management strategies and could lead to improved long-term outcomes. In this review we summarize objective and subjective instruments for evaluating physical activity and focus on interventions such as pulmonary rehabilitation or bronchodilators aimed at increasing activity levels. To date, only limited evidence exists to support the effectiveness of these interventions. We suggest that a multimodal approach comprising pulmonary rehabilitation, pharmacotherapy, and counselling programs aimed at addressing emotional and behavioural aspects of COPD may be an effective way to increase physical activity and improve health status in the long term.     

Growth and inorganic composition of ‘Nova’ mandarin plants grafted on two commercial rootstocks in response to salinity and silicon

The effects of salinity and its combination with silicon (Si) were studied in ‘Nova’ mandarin plants grafted on Citrus aurantium L. or Swingle Citrumelo to determine: (1) which combination is more tolerant to salt stress and (2) the impact of Si in limiting the harmful effects of salinity. Six groups of plants were grown in a greenhouse for 120 days and irrigated with: (1) 50 % Hoagland’s solution (Control), (2) 50 % Hoagland’s solution plus 80 mM NaCl (NaCl), and (3) 50 % Hoagland’s solution plus 80 mM NaCl plus 0.5 mM Si (NaCl + Si). Grafted plants exhibited accumulation of Na and Cl in their tissues following exposure to salinity. The ability of S. Citrumelo to retain the toxic ions in the roots in corroboration with the observation that the dry weights (DWs) of S. Citrumelo tissues were not influenced by NaCl treatment indicates that this rootstock is more tolerant to salinity. Silicon supplementation into the saline medium promoted the accumulation of toxic ions, whereas, when compared to NaCl treatment, it increased the DW of S. Citrumelo roots. Mineral concentrations were significantly affected by rootstock, treatment, and their interaction with S. Citrumelo, which presented better nutrient status than Sour Orange; and Si which differed depending on citrus tissue. It appears that S. Citrumelo rootstock is the most tolerant for ‘Nova’ mandarin plants under salinity, whereas salt tolerance in grafted citrus plants is not improved by Si application, indicating that the beneficial role of Si depends on the cultivar or rootstock–scion combinations.