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While the microtubule end-binding protein, EB1 facilitates early stages of HIV-1 infection, how it does so remains unclear. Here, we show that beyond its effects on microtubule acetylation, EB1 also indirectly contributes to infection by delivering the plus-end tracking protein (+TIP), cytoplasmic linker protein 170 (CLIP170) to the cell periphery. CLIP170 bound to intact HIV-1 cores or in vitro assembled capsid-nucleocapsid complexes, while EB1 did not. Moreover, unlike EB1 and several other +TIPs, CLIP170 enhanced infection independently of effects on microtubule acetylation. Capsid mutants and imaging revealed that CLIP170 bound HIV-1 cores in a manner distinct from currently known capsid cofactors, influenced by pentamer composition or curvature. Structural analyses revealed an EB-like +TIP-binding motif within the capsid major homology region (MHR) that binds SxIP motifs found in several +TIPs, and variability across this MHR sequence correlated with the extent to which different retroviruses engage CLIP170 to facilitate infection. Our findings provide mechanistic insights into the complex roles of +TIPs in mediating early stages of retroviral infection, and reveal divergent capsid-based EB1 mimicry across retroviral species.
Pinching, deviated wrist postures, and repetitive motion are risk factors for carpal tunnel syndrome. Hypervascularization of the median nerve and increased intraneural blood flow proximal to the carpal tunnel result in finger force and deviated wrist postures. The purpose of this study was to determine the effects of pinching with and without force, wrist posture, and repetitive wrist motion on intraneural blood flow in the median nerve.
Eleven healthy and 11 carpal tunnel syndrome-symptomatic individuals completed 3 sections of this study 15 pinch posture force trials, 3 repetitive wrist motion trials, and 3 static wrist posture trials. Intraneural blood flow (centimeters per second) was measured with pulsed wave Doppler ultrasound during each trial. Transverse B-mode images obtained from static trials were used to calculate the median nerve cross-sectional area and circumference.
An analysis of variance statistical analysis revealed significant main effects of pinch posture force (F
= 21.397; P < .001) and wrist posture (F
= 14.545; P < .001). Intraneural blood flow velocities were significantly greater when 6 N of force was applied by the thumb, finger, or pinch compared to no applied force in the same postures. Intraneural blood flow velocities were higher at 30° wrist flexion (mean ± SD, 2.24 ± 0.42 cm/s) than neutral (2.06 ± 0.45 cm/s) and 30° wrist extension (1.97 ± 0.46 cm/s). No changes were found in response to repetitive wrist motion.
Flexed wrists as well as applied finger and thumb forces increase median nerve blood flow at the entry to the carpal tunnel, which may negatively affect the median nerve.
Flexed wrists as well as applied finger and thumb forces increase median nerve blood flow at the entry to the carpal tunnel, which may negatively affect the median nerve.Implementing two-way strategies to enhance the lipid production in Rhodotorula mucilaginosa with the help of metabolic engineering was focused on the overexpression of acetyl coenzyme A carboxylase (ACC1 carboxylase) gene and repression of 3-hydroxy 3-methylglutaryl reductase (HMG-CoA reductase). Using an inducer (sodium citrate) and inhibitor (rosuvastatin), the amounts of biomass, lipid, and carotenoid were estimated. In the presence of inhibitor (200 mM), 62% higher lipid concentration was observed, while 44% enhancement was recorded when inducer (3 mM) was used. A combination of both inhibitor and inducer resulted in a 57% increase in lipid concentration by the oleaginous yeast. These results were again confirmed by real-time polymerase chain reaction by targeting the expression of the genes coding for ACC1 carboxylase and 13-fold increase was recorded in the presence of inducer as compared with control. This combined strategy (inducer and inhibitor use) has been reported for the first time as far as the best of our knowledge. The metabolic engineering strategies reported here will be a powerful approach for the enhanced commercial production of lipids.
Infantile hemangiomas (IHs) are the most common benign tumors in children. Color Doppler ultrasound is a noninvasive imaging modality that can show subclinical anatomic parameters in a wide range of dermatologic conditions. The purpose of this study was to describe the ultrasound characteristics of IHs and look for subclinical features with the potential to influence the involution and therapeutic response.
A review of the ultrasound database of children with clinical and ultrasound IH diagnoses was conducted. The clinically reported duration and the ultrasound assessment of the proliferative phase were compared. BYL719 concentration Descriptive and statistical analyses of qualitative and quantitative parameters of the series were performed. Significance was set at P < .05.
A total of 204 IHs were included. Twenty percent had arteriovenous shunts; 15% had afferent branches from main regional arteries; and almost 30% showed involvement of deep structures. Sixty-one percent of IHs were in the head and neck. Deep hemangiomas showed significantly thicker lesional vessels. A prolonged proliferative stage was significantly associated with a higher presence of arteriovenous shunts and a higher peak systolic velocity of the arterial vessels (≥15 cm/s) within the lesions.
Color Doppler ultrasound can support the detection of subclinical anatomic features that may potentially influence the involution and response to treatment of IHs. Some of these characteristics may serve as potential markers to predict and manage IHs in prolonged proliferative stages.
Color Doppler ultrasound can support the detection of subclinical anatomic features that may potentially influence the involution and response to treatment of IHs. Some of these characteristics may serve as potential markers to predict and manage IHs in prolonged proliferative stages.
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