Cochlear ribbon synapse maturation requires Nlgn1 and Nlgn3

Hearing depends on precise synaptic transmission between cochlear inner hair cells and spiral ganglion neurons through afferent ribbon synapses. Neuroligins (Nlgns) facilitate synapse maturation in the brain, but they have gone unstudied in the cochlea. We repor

CMS physics technical design report : Addendum on high density QCD with heavy ions

Peer reviewe

Closing the policy-practice gap in the management of child contacts of tuberculosis cases in developing countries.

Philip Campbell Hill and colleagues propose using a health needs assessment framework, research tools, and a strategy for clinical evaluation to help better manage child contacts of adult TB cases

A health needs assessment framework for addressing the policy-practice gap in the management of child contacts of TB cases.

<p>A health needs assessment framework for addressing the policy-practice gap in the management of child contacts of TB cases.</p

Indicators of system performance in child TB case contact management.

a<p>Index cases interviewed at diagnosis to identify case, contact, and household factors associated with non-attendance. A study of 500 contacts is advised, assuming non-attendance of at least 20%.</p>b<p>Cohort study of 500 enables evaluation of risk factors for non-adherence (taking <80% of doses) and temporary defaulting (not taking medicine for at least one week), assuming at least 20% non-adherence; enlarged to 1,000 assuming permanent default rate is at least 10%.</p>c<p><i>n</i> = 2,000 is estimated to identify “secondary cases” on the basis of 60%–90% efficacy of preventive therapy, an assumption of >80% adherence and a natural progression off treatment of up to 20% over one year <a href="http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.1001105#pmed.1001105-Marais1" target="_blank">[2]</a>.</p>d<p>Cohort of 200 is based on an expected incidence of symptomatic hepatotoxicity due to IPT of <10% over a treatment course in children <a href="http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.1001105#pmed.1001105-Devrim1" target="_blank">[25]</a>.</p

Examples of possible options analyses and recommendations to address gaps that are identified in the management of child contacts of adult TB cases.

<p>DOT, directly observed therapy; INH, Isoniazid; RIF, rifampicin.</p

Cochlear ribbon synapse maturation requires Nlgn1 and Nlgn3

Hearing depends on precise synaptic transmission between cochlear inner hair cells and spiral ganglion neurons through afferent ribbon synapses. Neuroligins (Nlgns) facilitate synapse maturation in the brain, but they have gone unstudied in the cochlea. We report Nlgn3 and Nlgn1 knockout (KO) cochleae have fewer ribbon synapses and have impaired hearing. Nlgn3 KO is more vulnerable to noise trauma with limited activity at high frequencies one day after noise. Furthermore, Nlgn3 KO cochleae have a 5-fold reduction in synapse number compared to wild type after two weeks of recovery. Double KO cochlear phenotypes are more prominent than the KOs, for example, 5-fold smaller synapses, 25% reduction in synapse density, and 30% less synaptic output. These observations indicate Nlgn3 and Nlgn1 are essential to cochlear ribbon synapse maturation and function