SummaryThe structural and functional plasticity of synapses is critical for learning and memory. Long-term potentiation (LTP) induction promotes spine growth and AMPAR accumulation at excitatory synapses, leading to increased synaptic strength. Glutamate initiates these processes, but the contribution from extracellular modulators is not fully established. Wnts are required for spine formation; however, their impact on activity-mediated spine plasticity and AMPAR localization is unknown. We found that LTP induction rapidly increased synaptic Wnt7a/b protein levels. Acute blockade of endogenous Wnts or loss of postsynaptic Frizzled-7 (Fz7) receptors impaired LTP-mediated synaptic strength, spine growth, and AMPAR localization at synapses. Live imaging of SEP-GluA1 and single-particle tracking revealed that Wnt7a rapidly promoted synaptic AMPAR recruitment and trapping. Wnt7a, through Fz7, induced CaMKII-dependent loss of SynGAP from spines and increased extrasynaptic AMPARs by PKA phosphorylation. We identify a critical role for Wnt-Fz7 signaling in LTP-mediated synaptic accumulation of AMPARs and spine plasticity.
Sleep nasendoscopy was conceived at the Royal National Throat, Nose and Ear Hospital, UK in 1991, and has remained fully implemented in patient selection for targeted treatment of the spectrum of sleep-disordered breathing. The senior authors (B.T.K. and P.B.) have been performing sleep nasendoscopy together for over 10 years, and we look back at their decade's experience. A retrospective audit study based on case notes was performed over a 10-year period (1995-2005) in a tertiary-referral practice setting. Case notes were retrieved on all patients who had undergone sleep nasendoscopy during the study period, and agreed data were extracted and analyzed. A total of 2,485 sleep nasendoscopies were performed in patients with a mean age of 44.1 years, a 4:1 male preponderance, and a mean body mass index of 27.3 kg m(-2). Sleep nasendoscopy grading correlated well with apnoea-hypopnoea index and mean oxygen desaturation. Such grading helped us define and discuss treatment options with patients. After a median follow-up period of 518 days, 72% of patients reported feeling better; 26% of patients reported no change; and only 2% of patients reported feeling worse after treatment. Sleep nasendoscopy has proved to be a useful adjunctive method to identify the anatomical site of snoring, not to mention upper airway collapse, and remains integral to our tertiary-referral practice. It has allowed us quality assessment of the dynamic anatomy of sleep-disordered breathing that most closely and cost-effectively simulates the natural situation of patients. And for targeted treatment, such assessment has been fundamental.
We demonstrate that live donor Veillonella dispar cells can transfer the conjugative transposon Tn916 to four different Streptococcus spp. recipients in a multispecies oral consortium growing as a biofilm in a constant depth film fermentor. Additionally, we demonstrate that purified V. dispar DNA can transform Streptococcus mitis to tetracycline resistance in this experimental system. These data show that transfer of conjugative transposon-encoded antibiotic resistance can occur by transformation in addition to conjugation in biofilms.
In the mid-19th century, thyroid surgery was regarded as a "proceeding by no means to be thought of" in Britain, "foolhardy" in Europe, and "horrid butchery" in America. By the mid-20th century, thyroid surgery was amongst the most efficient and safest of operations. This transition of modern thyroid surgery over a century was brought about by seven surgeons. The lessons of Theodor Billroth, Theodor Kocher, William Halsted, Charles Mayo, George Crile, Frank Lahey and Thomas Dunhill are to be forever relearned and respected. Let us remember this pantheon of pioneers, these "Magnificent Seven".
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.