ASSESSiNG tHE iMPACt oF ALCoHoL USE oN CoMMUNitiES

Release notes for dense-core vesicles V an de Bospoort et al. describe how Munc13 proteins control when and where dense-core vesicles (DCVs) are released from neurons. Neuronal DCVs contain neuropeptides and other factors that promote brain development and modulate synaptic transmission. Like neurotransmitter-containing synaptic vesicles (SVs), DCVs are released in response to action potentials and calcium infl ux, but relatively little is known about how neurons control DCV secretion. Van de Bospoort et al. designed a fluorescent probe to monitor the release of individual DCVs from hippocampal neurons in vitro. Though DCVs weren't enriched in synaptic terminals, they were preferentially secreted at synapses upon neuronal stimulation. DCV release from other parts of the neuron was less effi cient and required prolonged stimulation. To investigate why DCVs are secreted more effi ciently at synapses, Van de Bospoort et al. examined the Munc13 family of presynaptic proteins, which, by helping to assemble the SV fusion machinery, are essential for SV release. DCVs were still secreted from neurons lacking Munc13 proteins , but their release required prolonged stimulation and no longer occurred preferentially at synapses. When Munc13-1 was overex-pressed, on the other hand, it localized throughout neurons and boosted the effi ciency of extrasynaptic DCV release, such that brief stimuli induced secretion equally from synaptic and nonsynaptic sites. Therefore, although Munc13 proteins aren't required for DCV exocytosis, they facilitate secretion at synaptic termini. The researchers now want to investigate how DCVs are recruited into synapses and to determine why DCV and SV secretion are regulated differently. Opening up the ER's gatekeeper T rueman et al. describe how the Sec61 channel decides whether to open up and let proteins pass through it into the endoplasmic reticulum (ER). Proteins are directed to the ER by hydrophobic signal sequences and by cytosolic accessory factors that deliver them— either co-or posttranslationally—to Sec61 channels in the ER membrane. To permit protein translocation, Sec61's ␣ subunit undergoes a conformational change that unblocks its central pore and opens up a " lateral gate " through which signal sequences can be inserted into the channel. To understand how this conforma-tional change is triggered, Trueman et al. focused on a cluster of polar residues on either side of the lateral gate and on an adjacent patch of apolar residues in Sec61␣'s " plug domain, " which blocks the central pore when the channel is closed. Replacing these residues with polar amino acids …


ASSESSiNG tHE iMPACt oF ALCoHoL USE oN CoMMUNitiES
C ommunity indicators are used to assess the impact of alcohol on communities. For communities, indicator data can be used to inform prioritysetting agendas by identifying specific concerns within a community, guide policy and education initiatives, monitor community status on a particular measure over time or in comparison with other communities, and evaluate programs or policies. This article by Drs. Andrea Flynn and Samantha Wells reviews the main data sources for community indicators, discusses their strengths and limitations, and discusses indicators used in reference to four main topics relating to alcohol use and problems at the community level: alcohol use, patterns, and problems; alcohol availability; alcohol-related health outcomes/trauma; and alcoholrelated crime and enforcement. (pp. 135-149)

FoCUS oN: ALCoHoL AND MoRtALitY
A lcohol consumption has long been recognized as a risk factor for mortality. By combining data on alcohol per capita consumption, alcohol-drinking status and alcohol-drinking patterns, risk relationships, and mortality, the Comparative Risk Assessment Study estimated alcohol-attributable mortality for 1990 and 2010. In this article, Drs. Jürgen Rehm and Kevin D. Shield discuss alcohol's role in the global burden of mortality. (pp. 174-183)

FoCUS oN CHiLDREN AND PREADoLESCENtS
B ecause there are few surveillance studies of alcohol use and alcoholrelated problems among children and preadolescents, estimating the alcohol burden in this population is especially difficult. This article by Dr. John E. Donovan summarizes information from U.S. national and Statewide surveys on the prevalence of alcohol use among children in grades 6 and lower. Although the rates of alcohol use are relatively low in this population, substantial numbers of children do in fact have experience with alcohol. Limited available data highlight the need for better ongoing surveillance of this population. Although alcohol burden in children appears relatively low, it is increased through the alcohol use and abuse of their parents, and through the increased likelihood among early drinkers of alcohol problems and other negative outcomes in adolescence and young adulthood. (pp. 186-192)  10th-, and 12th-grade students assessing their alcohol use, thereby allowing researchers to better understand adolescents' consumption patterns during this vulnerable developmental period. These surveys have found high prevalence of drinking and binge drinking by the time students leave high school, report Drs. Megan E. Patrick and John E. Schulenberg. The authors also discuss the factors that influence adolescent alcohol use, such as parent and peer relationships, school and work, behavioral and drug-use problems, or personality characteristics, as well as review potential long-term effects of adolescent alcohol consumption. (pp. 193-200)

ExCESSivE ALCoHoL CoNSUMPtioN AND RELAtED CoNSEqUENCES AMoNG CoLLEGE StUDENtS
R esearch shows that multiple factors influence college drinking, from an individual's genetic susceptibility to the positive and negative effects of alcohol, alcohol use during high school, campus norms related to drinking, expectations regarding the benefits and detrimental effects of drinking, penalties for underage drinking, parental attitudes about drinking while at college, whether one is member of a Greek organization or involved in athletics, and conditions within the larger community that determine how accessible and affordable alcohol is. This article by Drs. Aaron White and Ralph Hingson examines recent findings about the causes and consequences of excessive drinking among college students relative to their noncollege peers and many of the strategies used to collect and analyze relevant data, as well as the inherent hurdles and limitations of such strategies. (pp.

FoCUS oN: WoMEN AND tHE CoStS oF ALCoHoL USE
A lthough there are proven beneficial effects associated with light-to-moderate drinking, such levels of drinking also are associated with increased risks of breast cancer and liver problems, and heavy drinking increases risks of hypertension and bone fractures and injuries. In addition, women's heavy-drinking patterns and alcohol use disorders are associated with increased likelihood of many psychiatric problems, including depression, posttraumatic stress disorder, eating disorders, and suicidality, as well as increased risks of intimate partner violence and sexual assault. In this article, Drs.