Slo1 Tail Domains, but Not the Ca2+ Bowl, Are Required for the β1 Subunit to Increase the Apparent Ca2+ Sensitivity of BK Channels

Functional large-conductance Ca2+- and voltage-activated K+ (BK) channels can be assembled from four α subunits (Slo1) alone, or together with four auxiliary β1 subunits to greatly increase the apparent Ca2+ sensitivity of the channel. We examined the structural features involved in this modulation with two types of experiments. In the first, the tail domain of the α subunit, which includes the RCK2 (regulator of K+ conductance) domain and Ca2+ bowl, was replaced with the tail domain of Slo3, a BK-related channel that lacks both a Ca2+ bowl and high affinity Ca2+ sensitivity. In the second, the Ca2+ bowl was disrupted by mutations that greatly reduce the apparent Ca2+ sensitivity. We found that the β1 subunit increased the apparent Ca2+ sensitivity of Slo1 channels, independently of whether the α subunits were expressed as separate cores (S0-S8) and tails (S9-S10) or full length, and this increase was still observed after the Ca2+ bowl was mutated. In contrast, β1 subunits no longer increased Ca2+ sensitivity when Slo1 tails were replaced by Slo3 tails. The β1 subunits were still functionally coupled to channels with Slo3 tails, as DHS-I and 17 β-estradiol activated these channels in the presence of β1 subunits, but not in their absence. These findings indicate that the increase in apparent Ca2+ sensitivity induced by the β1 subunit does not require either the Ca2+ bowl or the linker between the RCK1 and RCK2 domains, and that Slo3 tails cannot substitute for Slo1 tails. The β1 subunit also induced a decrease in voltage sensitivity that occurred with either Slo1 or Slo3 tails. In contrast, the β1 subunit–induced increase in apparent Ca2+ sensitivity required Slo1 tails. This suggests that the allosteric activation pathways for these two types of actions of the β1 subunit may be different

Evaluation of an Intervention Providing HPV Vaccine in Schools

To conduct outcome and process evaluations of school-located HPV vaccination clinics in partnership with a local health department

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Evaluation of an Intervention Providing HPV Vaccine in Schools

OBJECTIVES: To conduct outcome and process evaluations of school-located HPV vaccination clinics in partnership with a local health department. METHODS: Temporary clinics provided the HPV vaccine to middle school girls in Guilford County, North Carolina, in 2009–2010. RESULTS: HPV vaccine initiation was higher among girls attending host schools than satellite schools (6% vs. 1%, OR = 6.56, CI = 3.99–10.78). Of the girls who initiated HPV vaccine, 80% received all 3 doses. Private insurance or federal programs paid for most vaccine doses. CONCLUSIONS: Lessons learned for creating more effective school-health department partnerships include focusing on host schools and delivering several vaccines to adolescents, not just HPV vaccine alone

Addressing Staff Sexual Misconduct With Offenders Curriculum (Instructor’s Guide: Staff Sexual Misconduct With Offenders)_2004

Addressing Staff Sexual Misconduct with Offenders is a 36-hour training program that focuses on the complex issues surrounding staff sexual misconduct with offenders in all correctional settings. This training is designed for correctional policy makers, agency managers and administrators, and community leaders who influence correctional policy. In this guide you will find a suggested program agenda for this training which will provide the instructor with a snap-shot of the training program as a whole. You will also find an overview of each training module, resources you will need, and activities which you may find helpful in the execution of the training modules. The “Teaching Tips” section will offer suggestions on how you, the instructor may: Select trainers and guest speakers Prepare for the upcoming training sessions Set up for the training sessions Get to know your audience Use the curriculum Teach as a team Teach with maximum effectiveness for your specific audience Handle challenging people Respond to questions The goals of the Addressing Staff Sexual Misconduct with Offenders training is to: Define staff sexual misconduct with offenders Increase the understanding of the scope of staff sexual misconduct issues Familiarize training participants with state laws prohibiting staff sexual misconduct with offenders Introduce training participants to the nature and role of their power within correctional settings Review the components of a good policy about staff sexual misconduct with offenders would include Develop a realistic plan of action for agency’s activities to address staff sexual misconduct with offenders Understand the significance of agency culture and its affects and impact on staff sexual misconduct with offenders Examine agency’s management and operational practices that affect staff sexual misconduct Staff Sexual Misconduct With Offenders Instructor’s Guide 2004 6 Look at the training agendas of all agency staff Understand the issues involved in investigations of staff sexual misconduct with offenders Understand the human resources issues surrounding staff sexual misconduct from the perspective of the agency, the employee, and the offender Understand the legal considerations involved in allegations of staff sexual misconduct with offenders Identify elements of effective ways to interact with the media and community surrounding issues of staff sexual misconduct Understand ways to prevent staff sexual misconduct with offender

Factors influencing the success of male introductions into groups of female rhesus macaques: Introduction technique, male characteristics and female behavior

In captive populations of rhesus macaques, novel adult males are commonly introduced to female groups every few years to prevent inbreeding, which mimics male dispersal in wild macaque populations. However, introducing adult males is challenging because macaques are aggressive to newcomers, which can result in serious injuries. Efforts to reduce trauma risk during the introduction process and increase the probability of success are needed. Here we investigate the impact of multiple factors, including male attributes (e.g., age, weight, rank, and experience), introduction method (punctuated vs. continual exposure to females), and female behavior, on males' trauma risk and integration success. We studied eight introductions of multimale cohorts (3-7 males each; N = 36 total) into existing female groups of rhesus macaques at the Yerkes National Primate Research Center. Four cohorts were introduced using the punctuated exposure method where adult males were moved each morning from run housing to the females' indoor enclosure and returned to run housing in the afternoon, and four cohorts were introduced using the continual exposure method where adult males were moved to an introduction enclosure attached to the females' outdoor compound, allowing males to live in protected contact next to the female group continuously. Generalized linear mixed models fitted to trauma risk (e.g., latency to first trauma; total trauma count) and success or failure to integrate (i.e., continual residence within the female group for greater than 53% of days within a 28-day window after first overnight stay) showed that continual exposure to females in the introduction enclosure reduced male trauma risk and increased the likelihood of successful integration compared to punctuated exposure. Males received less trauma when they received a higher rate of grooming from females. Male attributes had no effect. These findings highlight the importance of introduction technique and female behavior in the process of males' social integration into female groups