This contribution describes measurements of lipid bilayer domain line tension based on two-dimensional thermal undulations of membranes with liquid ordered/liquid disordered phase coexistence and near-critical composition at room temperature. Lateral inhomogeneity of lipid and protein composition is currently a subject of avid research aimed at determining both fundamental properties and biological relevance of membrane domains. Line tension at fluid lipid bilayer membrane domain boundaries controls the kinetics of domain growth and therefore regulates the size of compositional heterogeneities. High line tension promotes membrane domain budding and fission. Line tension could therefore be an important control parameter regulating functional aspects of biological membranes. Here the established method of fluid domain flicker spectroscopy is applied to examine thermal domain wall fluctuations of phase-separated bilayer membranes. We find a Gaussian probability distribution for the first few excited mode amplitudes, which permits an analysis by means of appropriately specialized capillary wave theory. Time autocorrelation functions are found to decay exponentially, and relaxation times are fitted by means of a hydrodynamic theory relating line tensions and excited mode relaxation kinetics. Line tensions below 1 pN are obtained, with these two approaches yielding similar results. We examine experimental artifacts that perturb the Fourier spectrum of domain traces and discuss ways to identify the number of modes that yield reliable line tension information.
SUMMARYCerebellum development depends on the correct differentiation of progenitors into neurons, a process controlled by a transcriptional program that remains poorly understood. Here we show that neural-specific deletion of the BTB/POZ zinc-finger transcription factor-encoding gene Rp58 (Znf238, Zfp238) causes severe cerebellar hypoplasia and developmental failure of Purkinje neurons, Bergmann glia and granule neurons. Deletion of Rp58 in mouse embryonic Atoh1 + progenitors leads to strong defects in growth and foliation owing to its crucial role in the differentiation of granule neurons. Analysis of the Rp58 mutant at E14.5 demonstrates that Rp58 is required for the development of both glutamatergic and GABAergic neurons. Rp58 mutants show decreased proliferation of glutamatergic progenitors at E14.5. In addition, Rp58 ablation results in a reduced number of GABAergic Pax2 + neurons at E16.5 together with defects in the transcriptional program of ventricular zone progenitors. Our results indicate that Rp58 is essential for the growth and organization of the cerebellum and regulates the development of both GABAergic and glutamatergic neurons.
BACKGROUND AND OBJECTIVES: Pediatric orbital cellulitis/abscess (OCA) can lead to vision loss, intracranial extension of infection, or cavernous thrombosis if not treated promptly. No widely recognized guidelines exist for the medical management of OCA. The objective of this review was to summarize existing evidence regarding the role of inflammatory markers in distinguishing disease severity and need for surgery; the role of imaging in OCA evaluation; and the microbiology of OCA over the past 2 decades. METHODS: This review was reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Searches were performed in MEDLINE (Ovid), Web of Science Core Collection, Scopus, CINAHL (EBSCO), and Cochrane Central Register of Controlled Trials (CENTRAL), most recently on February 9, 2021. RESULTS: A total of 63 studies were included. Most were descriptive and assessed to have poor quality with high risk of bias. The existing publications evaluating inflammatory markers in the diagnosis of OCA have inconsistent results. Computed tomography imaging remains the modality of choice for evaluating orbital infection. The most common organisms recovered from intraoperative cultures are Streptococcus species (Streptococcus anginosus group, group A Streptococcus, and pneumococcus) and Staphylococcus aureus. Methicillin-resistant S aureus in culture-positive cases had a median prevalence of 3% (interquartile range, 0%-13%). CONCLUSION: This systematic review summarizes existing literature concerning inflammatory markers, imaging, and microbiology for OCA evaluation and management. High-quality evidence is still needed to define the optimal medical management of OCA.
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