A mutation in γ-tubulin alters microtubule dynamics and organization and is synthetically lethal with the kinesin-like protein Pkl1p

This is the publisher's version, also available electronically from "http://www.molbiolcell.org".Mitotic segregation of chromosomes requires spindle pole functions for microtubule nucleation, minus end organization, and regulation of dynamics. γ-Tubulin is essential for nucleation, and we now extend its role to these latter processes. We have characterized a mutation in γ-tubulin that results in cold-sensitive mitotic arrest with an elongated bipolar spindle but impaired anaphase A. At 30°C cytoplasmic microtubule arrays are abnormal and bundle into single larger arrays. Three-dimensional time-lapse video microscopy reveals that microtubule dynamics are altered. Localization of the mutant γ-tubulin is like the wild-type protein. Prediction of γ-tubulin structure indicates that non-α/β-tubulin protein–protein interactions could be affected. The kinesin-like protein (klp)Pkl1p localizes to the spindle poles and spindle and is essential for viability of the γ-tubulin mutant and in multicopy for normal cell morphology at 30°C. Localization and function of Pkl1p in the mutant appear unaltered, consistent with a redundant function for this protein in wild type. Our data indicate a broader role for γ-tubulin at spindle poles in regulating aspects of microtubule dynamics and organization. We propose that Pkl1p rescues an impaired function of γ-tubulin that involves non-tubulin protein–protein interactions, presumably with a second motor, MAP, or MTOC component

Pennsylvania Folklife Vol. 25, No. 1

• Pennsylvania German Tombstone Art of Lebanon County, Pennsylvania • Rain Day in Waynesburg, Pennsylvania • Non-Ordinary Stoneware Pieces from New Geneva and Greensboro, Pennsylvania • Pennsylvania German Astronomy and Astrology XIII: Conjunctions of 1683, 1694, and 1743 • The Social Context of Musical Instruments within the Pennsylvania German Culture • Tourism and the Amish Way of Life • Home Brewing Techniques: Folk-Cultural Questionnaire No. 41https://digitalcommons.ursinus.edu/pafolklifemag/1065/thumbnail.jp

The development of sentence-interpretation strategies in monolingual German-learning children with and without specific language impairment

Previous research on sentence comprehension conducted with German-learning children has concentrated on the role of case marking and word order in typically developing children. This paper compares, the performance of German-learning children with language impairment (age 4-6 years) and without language impairment (aged 2-6, 8-9 years) in two experiments that systematically vary the cues animacy, case marking; word-order, and subject-verb agreement. The two experiments differ with regard to the choice of case marking: in the first it is distinct but in the second it is neutralized. The theoretical framework is the competition model developed by Bates and Mac Whinney and their collaborators, a variant of the parallel distributed processing models. It is hypothesized that children of either population first appreciate the cue animacy that can be processed locally, that is, "on the spot," before they turn to more distributed cues leading ultimately up to subject-verb agreement, which presupposes the comparison of various constituents before an interpretation can be established. Thus agreement is more "costly" in processing than animacy or the (more) local cue initial NP. In experiment I with unambiguous case markers it is shown that the typically developing children proceed from animacy to the nominative (predominantly in coalition with the initial NP) to agreement, while in the second experiment with ambiguous case markers these children turn from animacy to the initial NP and then to agreement. The impaired children also progress from local to distributed cues. Yet, in contrast to the control group, they do not acknowledge the nominative in coalition with the initial NP in the first experiment but only in support of agreement. However, although they do not seem to appreciate distinct case markers to any large extent in the first experiment, they are irritated if such distinctions are lacking: in experiment II all impaired children turn to. animacy (some in coalition with the initial NP and/or particular word orders). In the discussion, the relationship between short-term memory and processing as well as the relationship between production and comprehension of case markers and agreement are addressed. Further research is needed to explore in more detail "cue costs" in sentence comprehension

Relationship between migraine history and breast cancer risk among premenopausal and postmenopausal women.

Both migraine and breast cancer are hormonally mediated diseases, and it is biologically plausible that women with a history of migraine may have a reduced breast cancer risk. However, this relationship has only been assessed in a single relatively small study that was unable to assess the effect of migraine triggers, which are also well-established breast cancer risk factors (e.g., use of alcohol and exogenous hormones), on the inverse association observed. Utilizing data on 4,568 breast cancer cases and 4,678 controls who participated in a multicenter population-based case-control study in the United States, we evaluated the association between migraine history and breast cancer risk using unconditional logistic regression. Migraine history data were obtained from structured in-person interviews. Women with a history of migraine had a reduced risk of breast cancer [odds ratio, 0.74; 95% confidence interval (CI), 0.66-0.82]. This risk did not differ by menopausal status, age at migraine diagnosis, use of prescription migraine medications, or when analyses were restricted to women who avoided various migraine triggers (including alcohol, exogenous hormones, and smoking). These data support a previous finding that a history of migraine may be associated with a reduced risk of breast cancer. It extends the prior report in observing that this relationship holds for both premenopausal and postmenopausal women and is independent of exposure to common migraine triggers

Risk Factors for SARS Transmission from Patients Requiring Intubation: A Multicentre Investigation in Toronto, Canada

In the 2003 Toronto SARS outbreak, SARS-CoV was transmitted in hospitals despite adherence to infection control procedures. Considerable controversy resulted regarding which procedures and behaviours were associated with the greatest risk of SARS-CoV transmission.A retrospective cohort study was conducted to identify risk factors for transmission of SARS-CoV during intubation from laboratory confirmed SARS patients to HCWs involved in their care. All SARS patients requiring intubation during the Toronto outbreak were identified. All HCWs who provided care to intubated SARS patients during treatment or transportation and who entered a patient room or had direct patient contact from 24 hours before to 4 hours after intubation were eligible for this study. Data was collected on patients by chart review and on HCWs by interviewer-administered questionnaire. Generalized estimating equation (GEE) logistic regression models and classification and regression trees (CART) were used to identify risk factors for SARS transmission. ratio ≤59 (OR = 8.65, p = .001) were associated with increased risk of transmission of SARS-CoV. In CART analyses, the four covariates which explained the greatest amount of variation in SARS-CoV transmission were covariates representing individual patients.Close contact with the airway of severely ill patients and failure of infection control practices to prevent exposure to respiratory secretions were associated with transmission of SARS-CoV. Rates of transmission of SARS-CoV varied widely among patients

The Long-Baseline Neutrino Experiment: Exploring Fundamental Symmetries of the Universe

The preponderance of matter over antimatter in the early Universe, the dynamics of the supernova bursts that produced the heavy elements necessary for life and whether protons eventually decay --- these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our Universe, its current state and its eventual fate. The Long-Baseline Neutrino Experiment (LBNE) represents an extensively developed plan for a world-class experiment dedicated to addressing these questions. LBNE is conceived around three central components: (1) a new, high-intensity neutrino source generated from a megawatt-class proton accelerator at Fermi National Accelerator Laboratory, (2) a near neutrino detector just downstream of the source, and (3) a massive liquid argon time-projection chamber deployed as a far detector deep underground at the Sanford Underground Research Facility. This facility, located at the site of the former Homestake Mine in Lead, South Dakota, is approximately 1,300 km from the neutrino source at Fermilab -- a distance (baseline) that delivers optimal sensitivity to neutrino charge-parity symmetry violation and mass ordering effects. This ambitious yet cost-effective design incorporates scalability and flexibility and can accommodate a variety of upgrades and contributions. With its exceptional combination of experimental configuration, technical capabilities, and potential for transformative discoveries, LBNE promises to be a vital facility for the field of particle physics worldwide, providing physicists from around the globe with opportunities to collaborate in a twenty to thirty year program of exciting science. In this document we provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess.Comment: Major update of previous version. This is the reference document for LBNE science program and current status. Chapters 1, 3, and 9 provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess. 288 pages, 116 figure