QSAR analysis of salicylamide isosteres with the use of quantum chemical molecular descriptors

Quantitative relationships between the molecular structure and the biological activity of 49 isosteric salicylamide derivatives as potential antituberculotics with a new mechanism of action against three Mycobacterial strains were investigated. The molecular structures were represented by quantum chemical B3LYP/6-31G* based molecular descriptors. A resulting set of 220 molecular descriptors, including especially electronic properties, was statistically analyzed using multiple linear regression, resulting in acceptable and robust QSAR models. The best QSAR model was found for Mycobacterium tuberculosis (r(2) = 0.92; q(2) = 0.89), and somewhat less good QSAR models were found for Mycobacterium avium (r(2) = 0.84; q(2) = 0.78) and Mycobacterium kansasii (r(2) = 0.80; q(2) = 0.56). All QSAR models were cross-validated using the leave-10-out procedure

Cell-Type-Specific Cytokinin Distribution within the Arabidopsis Primary Root Apex

Cytokinins (CKs) play a crucial role in many physiological and developmental processes at the levels of individual plant components (cells, tissues, and organs) and by coordinating activities across these parts. High-resolution measurements of intracellular CKs in different plant tissues can therefore provide insights into their metabolism and mode of action. Here, we applied fluorescence-activated cell sorting of green fluorescent protein (GFP)-marked cell types, combined with solid-phase microextraction and an ultra-high-sensitivity mass spectrometry (MS) method for analysis of CK biosynthesis and homeostasis at cellular resolution. This method was validated by series of control experiments, establishing that protoplast isolation and cell sorting procedures did not greatly alter endogenous CK levels. The MS-based method facilitated the quantification of all the well known CK isoprenoid metabolites in four different transgenic Arabidopsis thaliana lines expressing GFP in specific cell populations within the primary root apex. Our results revealed the presence of a CK gradient within the Arabidopsis root tip, with a concentration maximum in the lateral root cap, columella, columella initials, and quiescent center cells. This distribution, when compared with previously published auxin gradients, implies that the well known antagonistic interactions between the two hormone groups are cell type specific

The ASEAN community-based tourism standards: looking beyond certification

This paper reports findings from an opportunity study on the appropriateness of implementing community-based tourism standards (CBTS) certification through the Association of Southeast Asian Nations (ASEAN) criteria, as a way to improve sustainable tourism provision in the region. Framed by critical reflections on community-based tourism (CBT) literature and existing sustainable tourism standards (STS) practices, qualitative research consisting of interviews with six key industry experts provided core insights into a number of CBTS’ implementation challenges. Findings indicate the main hindering factors for the implementation of CBTS to be the lack of adequate governance, limited funding and insufficient community capacity. The study concluded that although at the moment the full implementation of CBTS as a certification programme would be premature, ASEAN-CBTS’ criteria are a useful benchmarking and strategic planning tool for local communities, which would eventually lead to improved CBT benefits, standards and performance in the region. At the same time, this paper argues that aspects including CBT competitiveness and service delivery need to be tackled first to create fruitful grounding for CBT certification

Protein secretion and outer membrane assembly in Alphaproteobacteria

The assembly of β-barrel proteins into membranes is a fundamental process that is essential in Gram-negative bacteria, mitochondria and plastids. Our understanding of the mechanism of β-barrel assembly is progressing from studies carried out in Escherichia coli and Neisseria meningitidis. Comparative sequence analysis suggests that while many components mediating β-barrel protein assembly are conserved in all groups of bacteria with outer membranes, some components are notably absent. The Alphaproteobacteria in particular seem prone to gene loss and show the presence or absence of specific components mediating the assembly of β-barrels: some components of the pathway appear to be missing from whole groups of bacteria (e.g. Skp, YfgL and NlpB), other proteins are conserved but are missing characteristic domains (e.g. SurA). This comparative analysis is also revealing important structural signatures that are vague unless multiple members from a protein family are considered as a group (e.g. tetratricopeptide repeat (TPR) motifs in YfiO, β-propeller signatures in YfgL). Given that the process of the β-barrel assembly is conserved, analysis of outer membrane biogenesis in Alphaproteobacteria, the bacterial group that gave rise to mitochondria, also promises insight into the assembly of β-barrel proteins in eukaryotes

Design, synthesis and in vitro evaluation of benzothiazole-based ureas as potential ABAD/17β-HSD10 modulators for Alzheimer’s disease treatment

This work was supported by the Ministry of Health of the Czech Republic (no. NV15-28967A), Charles University in Prague (no. GAUK B-CH/992214, SVV 260 291) and the Alzheimer’s Society (specifically The Barcopel Foundation). This research is part-funded by the MSD Scottish Life Sciences fund.Amyloid-beta peptide (Aβ) has been recognized to interact with numerous proteins, which may lead to pathological changes in cell metabolism of Alzheimer’s disease (AD) patients. One such known metabolic enzyme is mitochondrial amyloid-binding alcohol dehydrogenase (ABAD), also known as 17β-hydroxysteroid dehydrogenase type 10 (17β-HSD10). Altered enzyme function caused by the Aβ-ABAD interaction, was previously shown to cause mitochondrial distress and a consequent cytotoxic effect, therefore providing a feasible target in AD drug development. Based on previous frentizole derivatives studies, we report two novel series of benzothiazolyl ureas along with novel insights into the structure and activity relationships for inhibition of ABAD. Two compounds ( 37 , 39 ) were identified as potent ABAD inhibitors, where compound 39 exhibited comparable cytotoxicity with the frentizole standard; however, one-fold higher cytotoxicity than the parent riluzole standard. The calculated and experimental physical chemical properties of the most potent compounds showed promising features for blood-brain barrier penetration.PostprintPeer reviewe

Magnetic anisotropy in van-der-Waals ferromagnet VI3

A comprehensive study of magnetocrystalline anisotropy of a layered van-der-Waals ferromagnet VI3 was performed. We measured angular dependences of the torque and magnetization with respect to the direction of the applied magnetic field within the "ac" plane perpendicular to and within the basal ab plane, respectively. A two-fold butterfly-like signal was detected by magnetization in the perpendicular "ac" plane. This signal symmetry remains conserved throughout all magnetic regimes as well as through the known structural transition down to the lowest temperatures. The maximum of the magnetization signal and the resulting magnetization easy axis is significantly tilted from the principal c axis by ~40{\deg}. The close relation of the magnetocrystalline anisotropy to the crystal structure was documented. In contrast, a two-fold-like angular signal was detected in the paramagnetic region within the ab plane in the monoclinic phase, which transforms into a six-fold-like signal below the Curie temperature TC. With further cooling, another six-fold-like signal with an angular shift of ~30{\deg} grows approaching TFM. Below TFM, in the triclinic phase, the original six-fold-like signal vanishes, being replaced by a secondary six-fold-like signal with an angular shift of ~30{\deg}.Comment: 14 pages, 10 figure

Wound-on-tension for two drum winders

The two drum winder remains to be a high productivity winder for rewinding some paper and nonwoven webs at very high speeds. Winding models of varied capabilities exist for center winders, center winders with rider rollers, and surface winders. Winding models for two drum winders however are still in the introductory stages. Two drum winders are somewhat more complex than other winders due to the number of rollers, driven and undriven, which impinge the surface of the winding roll. The objectives of this paper are to show the influence of various winder operating parameters and thread path on the wound-on-tension in the outer layer (WOT).Mechanical and Aerospace Engineerin

Understanding Face and Shame: A Servant-Leadership and Face Management Model

Clergy can have a negative impact on churches and other individuals when they knowingly or unknowingly attempt to save face, that is, try to protect their standing or reputation. The desire to gain face and the fear of losing face and feeling ashamed will likely permeate clergy’s decision-making processes without even being noticed. This study explores the essence of face and face management and the relationship between face management and two characteristics of servant-leadership—awareness and healing—in both Chinese and American churches through the methodology of hermeneutic phenomenology. Prior to this study, to my knowledge, no hermeneutic phenomenological research of face management has been conducted in a church setting. Through a review of the literature, four areas are explored: face and shame, face management, servant-leadership, and face, shame, and face management within the church. This study obtained approval from the Institutional Review Board and informed consent from the participants. Three Chinese and three American Christian ministers were chosen to complete a question sheet and participate in two semi-structured interview sessions. A first cycle of open coding and second cycle of pattern coding were used during data analysis. Face experiences are discussed in light of eight major themes: body, triggers, becoming, face concepts, strategies, emotions, servant-leadership, and the church. Findings from the study help build a servant-leadership and face management model, which can offer an anchored approach for clergy and pastoral counselors to address face and shame and to develop therapeutic interventions