Knee flexors (mean [SD]; 49.9 [37.8%]) and ankle plantar flexors (46.6 [35.5%]) had the largest asymmetry indices. Hip and knee extensors had the lowest asymmetry indices (21.1 [18.1%] and 30.1 [24.7%], respectively) and the highest agreement between self-reported and objectively-determined more-affected lower limb (93.3 and 93.8, respectively). The hip extensor asymmetry index was correlated with the Fatigue Severity Scale (r = 0.542, p = 0.037). INTERPRETATION For the assessment of strength asymmetries in people with multiple sclerosis, it is suggested to 1) include measures of hip, knee, and ankle strength asymmetries, 2) include subjective perceptions and objective measures of strength asymmetries concurrently, and 3) to include measures of sensory function (proprioception). OBJECTIVES To investigate associations between sexual identity and low leisure-time physical activity (LTPA). STUDY DESIGN Cross-sectional study. METHODS The 2012 public health survey was conducted with a postal questionnaire in southern Sweden with 28,029 respondents, aged 18-80 years. Analyses were conducted with logistic regressions. RESULTS The prevalence of low LTPA among men and women were as follows 13.9% and 12.3% among heterosexuals, 26.1% and 18.5% among bisexuals, 19.5% and 15.6% among homosexuals, 26.6% and 18.5% among others. Bisexual men and women and other men had higher odds ratio of low LTPA than heterosexuals in the final models, whereas gay and lesbian participants did not differ. CONCLUSIONS The results should guide health promotion and prevention. Auxin is an important signaling molecule synthesized in organisms from multiple kingdoms of life, including land plants, green algae, and bacteria. In this review, we highlight the similarities and differences in auxin biosynthesis among these organisms. Tryptophan-dependent routes to IAA are found in land plants, green algae and bacteria. Recent sequencing efforts show that the indole-3-pyruvic acid pathway, one of the primary biosynthetic pathways in land plants, is also found in the green algae. These similarities raise questions about the origin of auxin biosynthesis. Future studies comparing auxin biosynthesis across kingdoms will shed light on its origin and role outside of the plant lineage. The voltage-gated potassium channel Kv1.3 is involved in multiple autoimmune diseases, such as multiple sclerosis, rheumatoid arthritis, diabetes mellitus type 1 and psoriasis. In many auto-immune diseases better treatment options are desired as existing therapies are often ineffective or become less effective over time, for which Kv1.3 inhibitors arise as promising candidates. In this study, five compounds were selected based on a 3D similarity searching methodology and subsequently screened ex vivo on the Kv1.3 channel. The screening resulted in two compounds inhibiting the Kv1.3 channel, of which TVS-12 was the most potent compound, while TVS-06 -although less potent- showed an excellent selectivity for Kv1.3. For both compounds the mechanism of action was investigated by an electrophysiological characterization on the Kv1.3 channel and three Kv1.3 mutants, designed to resemble the pore region of Kv1.2 channels. Structurally, the presence of a benzene ring and/or an oxane ring seems to cause a better interaction with the Kv1.3 channel, resulting in a 20-fold higher potency for TVS-12. Herein we present the synthesis and characterization of a novel chemical series of tadalafil analogues that display different pharmacological profiles. Compounds that have the 6R, 12aR configuration and terminal carboxylic acid group at the side chain arising from the piperazinedione nitrogen were potent PDE5 inhibitors, with compound 11 having almost equal potency to tadalafil and superior selectivity over PDE11, the most common off-target for tadalafil. Modifying the stereochemistry into 6S, 12aS configuration and adopting the hydroxamic acid moiety as a terminal group gave rise to compounds that only inhibited HDAC. Dual PDE5/HDAC inhibition could be achieved with compounds having 6R, 12aR configuration and hydroxamic acid moiety as a terminal group. The anticancer activity of the synthesized compounds was evaluated against a diverse number of cell lines of different origin. The compounds elicited anticancer activity against cell lines belonging to lymphoproliferative cancer as well as solid tumors. Despite the previous reports suggesting anticancer activity of PDE5 inhibitors, the growth inhibitory activity of the compounds seemed to be solely dependent on HDAC inhibition. https://www.selleckchem.com/products/hg106.html Compound 26 (pan HDAC IC50 = 14 nM, PDE5 IC50 = 46 nM) displayed the most potent anticancer activity in the present series and was shown to induce apoptosis in Molt-4 cells. HDAC isoform selectivity testing for compound 26 showed that it is more selective for HDAC6 and 8 over HDAC1 by more than 20-fold. Four new benzo[a]phenoxazinium chlorides with combinations of chloride, ethyl ester and methyl as terminals of the amino substituents were synthesized. These compounds were characterized and their optical properties were studied in absolute dry ethanol and water. Their antiproliferative activity was tested against Saccharomyces cerevisiae in a broth microdilution assay, along with an array of 36 other benzo[a]phenoxazinium chlorides. Minimum Inhibitory Concentration (MIC) values between 1.56 and >200 µM were observed. Fluorescence microscopy studies, used to assess the intracellular distribution of the dyes, showed that these benzo[a]phenoxazinium chlorides function as efficient and site specific probes for the detection of the vacuole membrane. The added advantage of some of the compounds, that displayed the lower MIC values, was the simultaneous staining of both the vacuole membrane and the perinuclear membrane of endoplasmic reticulum (ER). Molecular docking studies were performed on the human membrane protein oxidosqualene cyclase (OSC), using the crystal structure available on PDB (code 1W6K). The results showed that these most active compounds accommodated better in the active sites of ER enzyme OSC suggesting this enzyme as a potential target. As a whole, the results demonstrate that the benzo[a]phenoxazinium chlorides are interesting alternatives to the available commercial dyes. Changes in the substituents of these compounds can tailor both their staining specificity and antimicrobial activity.