Do myosins contribute to metastasis of prostate cancer cells?

Prostate cancer is the second most common cause of death from cancer in men in the UK. Localised disease can be treated with surgery or radiotherapy, but metastasis remains a great therapeutic challenge. Cancer cell migration involves rearrangements of the actin cytoskeleton, which is mediated by its interaction with myosins, a large and diverse family of motor proteins involved in many processes crucial for cell migration, such as cell adhesion, cell polarity or endocytosis. It is likely that the activity of myosins contributes to metastatic spread. I investigated the myosin expression profile in prostate cancer cell lines and found that Myo1b, Myo9b, Myo10 and Myo18a were expressed at higher levels in cells with high metastatic potential. Using an siRNA-based approach, knockdown of each myosin resulted in distinct phenotypes. Myo10 knockdown drastically decreased filopodia of PC3 cells, Myo18a knockdown increased filaments of non-muscle myosin 2A, knockdown of Myo1b and Myo9b increased stress fibre formation. Loss of Myo10 affected cell migration in 2D. In all cases, cell spread area was increased and 3D migration potential was decreased for Myo1b, Myo10 and Myo18a. Myo1b, Myo10 and Myo18a were also expressed in benign prostatic hyperplasia although knockdown of these myosins in benign tissue did not have very clear effects. Glioblastoma cells expressed high levels of Myo10 and showed decreased protrusions after Myo10 knockdown. Taken together, myosins act as molecular motors but also directly influence actin organisation and cell morphology and migration, which can contribute to the metastatic phenotype of cancer cells

Assessment of musculoskeletal symptoms in patients with psoriasis

Introduction. Psoriasis is a chronic autoimmune disease of skin which may affect around 2% of population and 20-40% of psoriatic patients develop psoriatic arthritis (PsA). It is estimated that cutaneous symptoms are present for about 10 years ahead of the musculoskeletal symptoms. Early diagnosis of arthritis and implementation of treatment are crucial for achieving remission and improved prognosis. Aim. The aim of the study was to assess the musculoskeletal symptoms in patients with psoriasis. Material and methods. 180 subjects with psoriasis of the skin and/ or nails were enrolled in the study. The screening questionnaire was developed to assess the frequency of musculoskeletal symptoms and their character. The symptoms reported by the patients were compared with the CASPAR classification criteria and with the screening questionnaire PEST. Results. More than 90% of respondents declared complaints from musculoskeletal system. In 70% of the surveyed, the symptoms were present at the time of completing the questionnaire and in 40% the reported symptoms fulfilled the criteria of inflammatory arthritis. 43% of the surveyed patients reported Achilles tendon pain and 42% reported dactylitis. The examined patients rarely reported back pain of inflammatory character (11%). In the study group nearly 40% of the patients were diagnosed with psoriatic arthritis. About 23% respondents (16/70) who reported symptoms fulfilling the criteria for psoriatic arthritis had not been previously diagnosed with rheumatic disease, and in patients reporting inflammatory back pain this figure amounted to 55% (10/18). Conclusions. Musculoskeletal complaints are frequent among patients with psoriasis. The significant percentage of patients treated by dermatologists do not have any diagnosis of inflammatory joint disease despite the presented symptoms.Wprowadzenie. Łuszczyca jest przewlekłą chorobą zapalną dotyczą- cą około 2% populacji. Spośród pacjentów z łuszczycą skóry 20-40% choruje na łuszczycowe zapalenie stawów (ŁZS). U większości osób zmiany skórne wyprzedzają objawy stawowe nawet o 10 lat. Wczesne rozpoznanie zapalenia stawów i zastosowanie leczenia jest kluczowe dla osiągnięcia remisji choroby i poprawy rokowania. Cel pracy. Celem pracy była ocena objawów ze strony układu mię- śniowo-szkieletowego wśród pacjentów z łuszczycą. Materiał i metody. Do badania włączono 180 osób z łuszczycą skóry i/lub paznokci. Opracowano ankietę oceniającą częstość występowania dolegliwości stawowych, a także ich natężenie i charakter. Zgłaszane przez chorych objawy zestawiono z kryteriami klasyfikacyjnymi CASPAR oraz ankietą przesiewową PEST. Wyniki. Ponad 90% osób ankietowanych zgłaszało dolegliwości bó- lowe ze strony układu mięśniowo-szkieletowego, u 70% występowały one w momencie badania, a u prawie 40% osób spełniały kryteria bólu zapalnego stawów. Ból przyczepu ścięgnistego (ścięgna Achillesa) zgłaszało 43% pacjentów, a zapalenie palca 42% respondentów. Dość rzadko pacjenci zgłaszali dolegliwości o charakterze zapalnym ze strony kręgosłupa (11% pacjentów). W grupie badanej blisko 40% osób miało zdiagnozowane łuszczycowe zapalenie stawów. Około 23% (16/70) osób zgłaszających dolegliwości spełniające kryterium bólu zapalnego stawów, nie posiadało dotychczas diagnozy choroby reumatycznej, pośród chorych zgłaszających ból zapalny kręgosłupa odsetek ten wynosił aż 55% (10/18). Wnioski. Dolegliwości ze strony układu mięśniowo-szkieletowego są powszechne wśród pacjentów chorujących na łuszczycę. Istotny odsetek chorych pozostających pod opieką lekarza dermatologa i spełniających kryteria dolegliwości o charakterze zapalnym nie posiada rozpoznania choroby stawów mimo prezentowanych objawów

Interplay of charge distribution and conformation in peptides: Comparison of theory and experiment

We assessed the correlation between charge distribution and conformation of flexible peptides by comparing the theoretically calculated potentiometric-titration curves of two model peptides, Ac–Lys5–NHMe (a model of poly-L-lysine) and Ac–Lys–Ala11–Lys–Gly2–Tyr–NH2 (P1) in water and methanol, with the experimental curves. The calculation procedure consisted of three steps: (i) global conformational search of the peptide under study using the electrostatically driven Monte Carlo (EDMC) method with the empirical conformational energy program for peptides (ECEPP)/3 force field plus the surface-hydration (SRFOPT) or the generalized Born surface area (GBSA) solvation model as well as a molecular dynamics method with the assisted model building and energy refinement (AMBER)99/GBSA force field; (ii) reevaluation of the energy in the pH range considered by using the modified Poisson–Boltzmann approach and taking into account all possible protonation microstates of each conformation, and (iii) calculation of the average degree of protonation of the peptide at a given pH value by Boltzmann averaging over conformations. For Ac–Lys5–NHMe, the computed titration curve agrees qualitatively with the experimental curve of poly-L-lysine in 95% methanol. The experimental titration curves of peptide P1 in water and methanol indicate a remarkable downshift of the first pKa value compared to the values for reference compounds (n-butylamine and phenol, respectively), suggesting the presence of a hydrogen bond between the tyrosine hydroxyl oxygen and the Hϵ proton of a protonated lysine side chain. The theoretical titration curves agree well with the experimental curves, if conformations with such hydrogen bonds constitute a significant part of the ensemble; otherwise, the theory predicts too small a downward pH shift.Fil: Makowska, Joanna. Universidad de Gdansk; Polonia. Cornell University; Estados UnidosFil: Bagińska, Katarzyna. Universidad de Gdansk; PoloniaFil: Kasprzykowski, F.. Universidad de Gdansk; PoloniaFil: Vila, Jorge Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto de Matemática Aplicada de San Luis "Prof. Ezio Marchi". Universidad Nacional de San Luis. Facultad de Ciencias Físico, Matemáticas y Naturales. Instituto de Matemática Aplicada de San Luis "Prof. Ezio Marchi"; Argentina. Cornell University; Estados UnidosFil: Jagielska, Anna. Cornell University; Estados UnidosFil: Liwo, Adam. Cornell University; Estados UnidosFil: Chmurzyński, Lech. Universidad de Gdansk; PoloniaFil: Scheraga, Harold A.. Cornell University; Estados Unido