Tug-of-war between two elastically coupled molecular motors: a case study on force generation and force balance

Intracellular transport is performed by molecular motors that pull cargos along cytoskeletal filaments. Many cellular cargos are observed to move bidirectionally, with fast transport in both directions. This behaviour can be understood as a stochastic tug-of-war between two teams of antagonistic motors. The first theoretical model for such a tug-of-war, the Muller-Klumpp-Lipowsky (MKL) model, was based on two simplifying assumptions: (i) both motor teams move with the same velocity in the direction of the stronger team, and (ii) this velocity matching and the associated force balance arise immediately after the rebinding of an unbound motor to the filament. In this study, we extend the MKL model by including an elastic coupling between the antagonistic motors, and by allowing the motors to perform discrete motor steps. Each motor step changes the elastic interaction forces experienced by the motors. In order to elucidate the basic concepts of force balance and force fluctuations, we focus on the simplest case of two antagonistic motors, one kinesin against one dynein. We calculate the probability distribution for the spatial separation of the motors and the dependence of this distribution on the motors' unbinding rate. We also compute the probability distribution for the elastic interaction forces experienced by the motors, which determines the average elastic force ?F? and the standard deviation of the force fluctuations around this average value. The average force ?F? is found to decrease monotonically with increasing unbinding rate ?0. The behaviour of the MKL model is recovered in the limit of small ?0. In the opposite limit of large ?0, ?F? is found to decay to zero as 1/?0. Finally, we study the limiting case with ?0 = 0 for which we determine both the force statistics and the time needed to attain the steady state. Our theoretical predictions are accessible to experimental studies of in vitro systems consisting of two antagonistic motors attached to a synthetic scaffold or crosslinked via DNA hybridization

Quantification of Plasma and Urine Thymidine and 2'-Deoxyuridine by LC-MS/MS for the Pharmacodynamic Evaluation of Erythrocyte Encapsulated Thymidine Phosphorylase in Patients with Mitochondrial Neurogastrointestinal Encephalomyopathy.

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is an ultra-rare disorder caused by mutations in TYMP, leading to a deficiency in thymidine phosphorylase and a subsequent systemic accumulation of thymidine and 2'-deoxyuridine. Erythrocyte-encapsulated thymidine phosphorylase (EE-TP) is under clinical development as an enzyme replacement therapy for MNGIE. Bioanalytical methods were developed according to regulatory guidelines for the quantification of thymidine and 2'-deoxyuridine in plasma and urine using liquid chromatography-tandem mass spectrometry (LC-MS/MS) for supporting the pharmacodynamic evaluation of EE-TP. Samples were deproteinized with 5% perchloric acid (v/v) and the supernatants analyzed using a Hypercarb column (30 × 2.1 mm, 3 µm), with mobile phases of 0.1% formic acid in methanol and 0.1% formic acid in deionized water. Detection was conducted using an ion-spray interface running in positive mode. Isotopically labelled thymidine and 2'-deoxyuridine were used as internal standards. Calibration curves for both metabolites showed linearity (r > 0.99) in the concentration ranges of 10-10,000 ng/mL for plasma, and 1-50 µg/mL for urine, with method analytical performances within the acceptable criteria for quality control samples. The plasma method was successfully applied to the diagnosis of two patients with MNGIE and the quantification of plasma metabolites in three patients treated with EE-TP

SEREBRAL DEV KİST HİDATİK

Human hydatid disease is endemic in Turkey and brain hydatosis is a childhood disease. The hydatid cysts of the brain are mostly single and 18% of the cases have another visceral involvement. The cysts may rarely reach to gigantic sizes in children. Here, we report a case of gigantic hydatid cyst of the brain in a seven years old boy who presented with signs of increased intracranial pressure. He was successfully operated with Dowling's surgical technique and he is still being followed up with no neurologic sequel. İnsan hidatik hastalığı Türkiye'de endemik olup, beyin hidatozisi çocukluk çağının hastalığıdır. Beyin hidatik kistleri sıklıkla tek olup vakaların %18'inde diğer viseral organlarda tutulum mevcuttur. Kistler çocukluk çağında nadiren çok büyük boyutlara ulaşmaktadır. Bu yazıda artmış kafa içi basıncı bulguları ile başvuran ve beyinde devasal boyutlarda hidatik kisti saptanan yedi yaşında erkek bir olgu sunulmaktadır. Hasta başarıyla Dowling's cerrahi tekniği ile opere edilmiş olup halen sekelsiz olarak takip edilmektedir

Acinetobacter türlerine bağlı kan dolaşımı infeksiyonlarında risk faktörleri: İleriye dönük bir olgu-kontrol çalışması

Objective: The aim of this prospective case control study was to describe the risk factors for bacteremia due to Acinetobacter species among hospitalized patients. Methods: The study was conducted prospectively from July 2012 to January 2014, and one case group and two control groups were created. Case group comprising patients with Acinetobacter bacteremia and control group 1 comprising patients with bacteremia due to other agents and control group 2 comprising non-bacteremic patients were compared in terms of demographic characteristics, underlying diseases, invasive procedures, and antibiotic use. Results: The study group (n=23) and control groups (n=46) were compared with univariate analysis and significant risk factors for Acinetobacter bacteremia were as follows: total parenteral nutrition, chemotherapy, use of broad spectrum antibiotics including β-lactam and β-lactamase inhibitors, carbapenems, teicoplanin, and antifungals (p<0.05). The duration of hospitalization was longer in case group (p=0.005). In multivariate analysis, factors independently associated with an increased risk of Acinetobacter spp. bacteremia included total parenteral nutrition (odds ratio, OR 5.13; confidence interval 95%, CI 95%, 1.41-18.57; p=0.013), use of a β-lactam/β-lactamase inhibitor (OR 7.67; CI 95% 1.67- 35.25; p=0.009), and use of teicoplanin (OR 4.11; CI 95% 1.09- 15.46; p=0.036). Conclusions: The definition of risk factors for Acinetobacter spp. bacteremia may help with the management of patients and infection control precautions by early prediction of the infection. © 2015, AVES Ibrahim Kara. All rights reserved

Aktivnost arginaze u ovarijskim strukturama krava švicarske smeđe pasmine i njezinih križanaca.

Arginase is the last enzyme of the urea cycle. It catalyses the hydrolysis of L-arginine to L-ornitine and urea. The aim of this study was to investigate the presence of arginase activity in ovarian structures such as: Graaf follicles, GF (Medium and Large size, M- and L-size), Corpus Haemorrhagicum (CH), and various types of Corpus Luteum (CL) such as: cyclic CL (CCL), 2-4 month pregnancy CL (2-4 MCL) and 4-7 month pregnancy CL (4-7 MCL). Ovarian tissues of 62 cows (7-10 years old and Brown Swiss or its cross-breeds), collected from a local slaughterhouse, were used as material. The materials were divided into 6 experimental groups, as follows: MGF group (n = 7), LGF group (n = 21), CH group (n = 7), CCL group (n = 6), 2-4 MCL group (n = 9) and 4-7 MCL group (n = 12). Arginase activities were measured as 0.056 ± 0.017, 0.100 ± 0.016, 2.517 ± 0.521, 0.827 ± 0.190, 0.674 ± 0.106 and 0.833 ± 0.093 U/mg protein in all groups, respectively. Arginase activity in the CH group was significantly higher than that in the CCL, 2-4 MCL and 4-7 MCL groups (P<0.001). The lowest enzyme activity was in the MGF and LGF groups. Hence, it was concluded that the arginase enzyme might play a crucial role in cell division, proliferation and differentiation in the ovarian tissues (especially the CH) of mature cows.Arginaza je posljednji enzim u ciklusu ureje koji katalizira hidrolizu L-arginina u L-ornitin i ureju. Cilj istraživanja bio je utvrditi prisutnost aktivnosti arginaze u ovarijskim strukturama kao što su Graafovi folikuli, GF (srednje veliki - M i veliki - L), corpus haemorrhagicum (CH) i različiti tipovi corpus luteum (CL) kao što su ciklični (CCL), 2-4 mjeseca graviditetni (2-4 MCL) i 4-7 mjeseci graviditetni (4-7 MCL). Tkiva ovarija od 62 krave (švicarske smeđe pasmine i križanaca u dobi od 7 do 10 godina) prikupljena su u lokalnoj klaonici. Materijali su bili podijeljeni u 6 pokusnih skupina kako slijedi: MGF skupina (n = 7), LGF skupina (n = 21), CH skupina (n = 7), CCL skupina (n = 6), 2-4 MCL skupina (n = 9) i 4-7 MCL skupina (n = 12). Slijedom navedenih skupina, aktivnost arginaze bila je 0,056 ± 0,017, 0,100 ± 0,016, 2,517 ± 0,521, 0,827 ± 0,190, 0,674 ± 0,106 i 0,833 ± 0,093 U/mg. Aktivnost arginaze u CH skupini bila je signifikantno viša u odnosu na skupine CCL, 2-4 MCL i 4-7 MCL (P<0,001). Najniža aktivnost enzima bila je u skupinama MGF i LGF. Zaključeno je o mogućoj ključnoj ulozi aktivnosti enzima arginaze u diobi stanica, proliferaciji i diferencijaciji ovarijskih tkiva (osobito CH) kod odraslih krava

Bilateral occipital arteries of internal carotid origin: report of a case and review of the literature

The present report describes a patient with bilateral occipital arteries of internal carotid origin, which is an extremely rare variation, and left vertebral artery ostial stenosis diagnosed by selective catheterization and digital subtraction angiography

Is amygdala size correlated with stress?

Background: One of the important mechanisms that regulate the stress response of the body is hypothalamic pituitary adrenal axis. One of the structures activating this axis is amygdala. We have seen people around who react calmer and cooler to very stressful situations. Are people with smaller amygdala really calmer? Or, can we say that the bigger the amygdala, which is the trigger of the body’s response to stress, the more a person panics? Aim of the study is to compare the saliva cortisol levels and amygdala volume.Materials and methods: Study conducted with 63 male students. Magnetic resonance images of students were taken before their final exam to calculate amygdala volumes. Saliva samples of all students were taken two times to detect cortisol levels in saliva. First one was 20 days before the final exam and second one was on the exam day. We assumed that the students were stressful on exam day.Results and Conclusions: No statistically significant correlation was found between saliva cortisol levels and amygdala volume in the study