Structure–activity relationship of 2,4-D correlates auxinic activity with the induction of somatic embryogenesis in Arabidopsis thaliana

2,4-dichlorophenoxyacetic acid (2,4-D) is a synthetic analogue of the plant hormone auxin that is commonly used in many in vitro plant regeneration systems, such as somatic embryogenesis (SE). Its effectiveness in inducing SE, compared to the natural auxin indole-3-acetic acid (IAA), has been attributed to the stress triggered by this compound rather than its auxinic activity. However, this hypothesis has never been thoroughly tested. Here we used a library of forty 2,4-D analogues to test the structure–activity relationship with respect to the capacity to induce SE and auxinic activity in Arabidopsis thaliana. Four analogues induced SE as effectively as 2,4-D and 13 analogues induced SE but were less effective. Based on root growth inhibition and auxin response reporter expression, the 2,4-D analogues were classified into different groups, ranging from very active to not active auxin analogues. A halogen at the 4-position of the aromatic ring was important for auxinic activity, whereas a halogen at the 3-position resulted in reduced activity. Moreover, a small substitution at the carboxylate chain was tolerated, as was extending the carboxylate chain with an even number of carbons. The auxinic activity of most 2,4-D analogues was consistent with their simulated TIR1-Aux/IAA coreceptor binding characteristics. A strong correlation was observed between SE induction efficiency and auxinic activity, which is in line with our observation that 2,4-D-induced SE and stress both require TIR1/AFB auxin co-receptor function. Our data indicate that the stress-related effects triggered by 2,4-D and considered important for SE induction are downstream of auxin signalling

CorNet : assigning function to networks of co-evolving residues by automated literature mining

CorNet is a web-based tool for the analysis of co-evolving residue positions in protein superfamily sequence alignments. CorNet projects external information such as mutation data extracted from literature on interactively displayed groups of co-evolving residue positions to shed light on the functions associated with these groups and the residues in them. We used CorNet to analyse six enzyme super-families and found that groups of strongly co-evolving residues tend to consist of residues involved in a same function such as activity, specificity, co-factor binding, or enantioselectivity. This finding allows to assign a function to residues for which no data is available yet in the literature. A mutant library was designed to mutate residues observed in a group of co-evolving residues predicted to be involved in enantioselectivity, but for which no literature data is available yet. The resulting set of mutations indeed showed many instances of increased enantioselectivity

Application of the New Classification on Patients with a Disorder of Sex Development in Indonesia

Disorder of sex development (DSD) patients in Indonesia most often do not receive a proper diagnostic evaluation and treatment. This study intended to categorize 88 Indonesian patients in accordance with the new consensus DSD algorithm. Diagnostic evaluation including clinical, hormonal, genetic, imaging, surgical, and histological parameters was performed. Fifty-three patients were raised as males, and 34 as females. Of 22 patients with 46, XX DSD, 15 had congenital adrenal hyperplasia, while in one patient, an ovarian Leydig cell tumor was found. In all 58 46, XY DSD patients, 29 were suspected of a disorder of androgen action (12 with an androgen receptor mutation), and in 9, gonadal dysgenesis was found and, in 20, severe hypospadias e.c.i. Implementation of the current consensus statement in a resource-poor environment is very difficult. The aim of the diagnostic workup in developing countries should be to end up with an evidence-based diagnosis. This is essential to improve treatment and thereby to improve the patients' quality of life

Risk factors for atherosclerotic and medial arterial calcification of the intracranial internal carotid artery

_Background and aims:_ Calcifications of the intracranial internal carotid artery (iICA) are an important risk factor for stroke. The calcifications can occur both in the intimal and medial layer of the vascular wall. The aim of this study is to assess whether medial calcification in the iICA is differently related to risk factors for cardiovascular disease, compared to intimal calcification. _Methods:_ Unenhanced thin slice computed tomography (CT) scans from 1132 patients from the Dutch acute stroke study cohort were assessed for dominant localization of calcification (medial or intimal) by one of three observers based on established methodology. Associations between known cardiovascular risk factors (age, gender, body mass index, pulse pressure, eGFR, smoking, hypertension, diabetes mellitus, hyperlipidemia, previous vascular disease, and family history) and the dominant localization of calcifications were assessed via logistic regression analysis. _Results:_ In the 1132 patients (57% males, mean age 67.4 years [SD 13.8]), dominant intimal calcification was present in 30.9% and dominant medial calcification in 46.9%. In 10.5%, no calcification was seen. Age, pulse pressure and family history were risk factors for both types of calcification. Multivariably adjusted risk factors for dominant intimal calcification only were smoking (OR 2.09 [CI 1.27–3.44]) and hypertension (OR 2.09 [CI 1.29–3.40]) and for dominant medial calcification diabetes mellitus (OR 2.39 [CI 1.11–5.14]) and previous vascular disease (OR 2.20 [CI 1.30–3.75]). _Conclusions:_ Risk factors are differently related to the dominant localizations of calcifications, a finding that supports the hypothesis that the intimal and medial calcification represents a distinct etiology

Bluetooth Broadcasting: How far can we go? An experimental study

Bluetooth is a wireless communication technology to build small networks of devices. It was designed as a cable replacement technology. Given its widespread adoption, especially in mobile devices, new uses are possible today. For instance, one can broadcast messages to nomadic users based on their location. In this paper, we perform an experimental evaluation of whether Bluetooth is indeed a suitable technology for spontaneous networking and broadcasting. The evaluation does not only consist of a review of current hardware and software, but also of a concrete implementation tested in a controlled indoor and in a not-controlled outdoor environment. The results of the experimentation show that, despite the intrinsic limitation of the original design, Bluetooth is indeed suitable for mobile location-based broadcasting.

A comparison of car ownership models

In this paper, car ownership models that can be found in the literature (with a focus on the recent literature and on models developed for transport planning) are classified into a number of model types. The different model types are compared on a number of criteria: inclusion of demand and supply side of the car market, level of aggregation, dynamic or static model, long-run or short-run forecasts, theoretical background, inclusion of car use, data requirements, treatment of business cars, car type segmentation, inclusion of income, of fixed and/or variable car cost, of car quality aspects, of licence holding, of socio-demographic variables and of attitudinal variables, and treatment of scrappage

Does Mindfulness Improve After Heart Coherence Training in Patients With Chronic Musculoskeletal Pain and Healthy Subjects?:A Pilot Study

BACKGROUND: Mindfulness and heart coherence training (HCT) training are applied increasingly in the treatment of patients with chronic musculoskeletal pain (CMP). Questionnaires have been developed to assess changes in mindfulness but no gold standard is available. OBJECTIVE: Explore the relationship between changes in mindfulness scores and changes in heart coherence after 3 sessions of HCT in patients with CMP and in healthy subjects. RESEARCH METHOD/DESIGN: Ten patients with CMP and 15 healthy subjects were trained in self-regulation with the use of HCT following a standardized stress relief program developed by the HeartMath Institute. A heart coherence-score (HC-score) was constructed with scores ranging from 0-100 with higher scores reflecting more heart rate variability (HRV) coherency. Change scores, Spearman correlation coefficients, and Wilcoxon Signed Rank test were calculated to test relationships and differences between HC-score, the Mindfulness Attention and Awareness Scale (MAAS) and Five Facet Mindfulness Questionnaire (FFMQ). A new questionnaire was constructed to explore on which mindfulness-related domains patients with CMP report changes after HCT. RESULTS: Increases were present on HC-score in healthy subjects (P<.01) and in patients (P<.01) between baseline and follow-up. Effect sizes on change on the MAAS and FFMQ were low. Weak (r<0.25) and non-significant correlations were observed in change scores between HC-score and MAAS or FFMQ. Patients reported significant favorable differences on 6 mindfulness related domains in the new questionnaire: breathing rhythm, physical awareness, positive or negative emotions, recognition of stressful situations, thoughts, and tendency to actively self-regulate. CONCLUSIONS: In this pilot study, mindfulness as assessed by the MAAS and FFMQ does not appear to improve after HCT. HRV coherency, MAAS, and FFMQ measure different constructs and are weakly related. It is of great importance to choose and develop valid measures that reflect patients' states of mindfulness. Content and face validity of measures of mindfulness may be considered in the light of performance-based measures