HSPB1 facilitates the formation of non-centrosomal microtubules

The remodeling capacity of microtubules (MT) is essential for their proper function. In mammals, MTs are predominantly formed at the centrosome, but can also originate from non-centrosomal sites, a process that is still poorly understood. We here show that the small heat shock protein HSPB1 plays a role in the control of non-centrosomal MT formation. The HSPB1 expression level regulates the balance between centrosomal and non-centrosomal MTs. The HSPB1 protein can be detected specifically at sites of de novo forming non-centrosomal MTs, while it is absent from the centrosomes. In addition, we show that HSPB1 binds preferentially to the lattice of newly formed MTs in vitro, suggesting that its function occurs by stabilizing MT seeds. Our findings open new avenues for the understanding of the role of HSPB1 in the development, maintenance and protection of cells with specialized non-centrosomal MT arrays

Continuity and Change in Higher Education Careers Services in England

This chapter charts key aspects of the work of Careers Services in Higher Education (HE) in England (1999-2020). It is organised into six main sections: 1. public policy and the rise of employability; 2. employability, tuition fee rises and marketisation; 3. evolution of professional identity and practice; 4. changes in student and graduate employment and work; 5. policy and practice trends (regionalisation and social mobility); and finally, 6. present and future challenges (big data and technology). Contextual issues are outlined, and Careers Service responses are explored addressing how the work of careers professionals has dramatically evolved during this period. Across the chapter, we reflect on developments in policy and context that influenced continuity and change in professional practices that lead us to the present-day and to consider key opportunities and challenges for the future

Johnson Space Center's Risk and Reliability Analysis Group 2008 Annual Report

The Johnson Space Center (JSC) Safety & Mission Assurance (S&MA) Directorate s Risk and Reliability Analysis Group provides both mathematical and engineering analysis expertise in the areas of Probabilistic Risk Assessment (PRA), Reliability and Maintainability (R&M) analysis, and data collection and analysis. The fundamental goal of this group is to provide National Aeronautics and Space Administration (NASA) decisionmakers with the necessary information to make informed decisions when evaluating personnel, flight hardware, and public safety concerns associated with current operating systems as well as with any future systems. The Analysis Group includes a staff of statistical and reliability experts with valuable backgrounds in the statistical, reliability, and engineering fields. This group includes JSC S&MA Analysis Branch personnel as well as S&MA support services contractors, such as Science Applications International Corporation (SAIC) and SoHaR. The Analysis Group s experience base includes nuclear power (both commercial and navy), manufacturing, Department of Defense, chemical, and shipping industries, as well as significant aerospace experience specifically in the Shuttle, International Space Station (ISS), and Constellation Programs. The Analysis Group partners with project and program offices, other NASA centers, NASA contractors, and universities to provide additional resources or information to the group when performing various analysis tasks. The JSC S&MA Analysis Group is recognized as a leader in risk and reliability analysis within the NASA community. Therefore, the Analysis Group is in high demand to help the Space Shuttle Program (SSP) continue to fly safely, assist in designing the next generation spacecraft for the Constellation Program (CxP), and promote advanced analytical techniques. The Analysis Section s tasks include teaching classes and instituting personnel qualification processes to enhance the professional abilities of our analysts as well as performing major probabilistic assessments used to support flight rationale and help establish program requirements. During 2008, the Analysis Group performed more than 70 assessments. Although all these assessments were important, some were instrumental in the decisionmaking processes for the Shuttle and Constellation Programs. Two of the more significant tasks were the Space Transportation System (STS)-122 Low Level Cutoff PRA for the SSP and the Orion Pad Abort One (PA-1) PRA for the CxP. These two activities, along with the numerous other tasks the Analysis Group performed in 2008, are summarized in this report. This report also highlights several ongoing and upcoming efforts to provide crucial statistical and probabilistic assessments, such as the Extravehicular Activity (EVA) PRA for the Hubble Space Telescope service mission and the first fully integrated PRAs for the CxP's Lunar Sortie and ISS missions

Prospectus, October 26, 1973

STAFF PROFILES; Trustees Welcome Stugo President Kendricks To Board; Chills Highlight Haunted House; Only Two Of Seven Amendments Pass, Original Report Incorrect; Prospectus In Perspective: Impeachment Now; The Short Circuit; Cruisin\u27 \u2773; Senator Hulsizer Asks For Student Involvement; Letters From Our Readers; To the Faculty of Parkland College; Bowling Bulletin Board; Death By Hunger; TARGET Explained At Open House; Behind The Books; Scott I Deal With The Issues ; Human Development Seminar Slated; The History Of The Controversial Film - Salt Of The Earth ; S.W.A.M.P. Not A Fad; News Bulletin; Allman Bros. Come Through On Brothers and Sisters; Johnson We Take The Student Where He Is, and Build On That ; Campus Continues To Be Completed; Pre-Registration Additional Info; Mutt and Mortie; Leaders To Meet At Allerton This Saturday, Sunday; Debaters Shows Strength At Bradley Tourney; Health Center Free Clinic; Day Senators Outline Platforms; Slave Auction, Dance Today; President Releases Tapes; Marshall Wins PCFW Scholarship; A\u27s Repeat As World Champs, Dump N.Y. Mets In Seven Games; Wrist-Wrestling, Frisbie Contests To Be Held Soon; Monday\u27s Coach; Harriers Lose Flores Burnette, Will Run In Region IV Finals On Saturday, October 26; Fast Freddy\u27s Football Forecast; Fast Freddy Pays In Cash, Too; Female Winner Of Fast Freddy; Classified Ads; Champaign To Pick Up Leaves; Masters\u27 \u27Spoon River\u27 Comes To Parkland; A Column By And For Women; What The Signs Say; W. Virginia U. Hires Attorney; Who Will Listen?; Final Exam Schedule - Fall Quarter; Callboard; Sharing Group Recommends Eighthttps://spark.parkland.edu/prospectus_1973/1003/thumbnail.jp

Small heat-shock protein HSPB1 mutants stabilize microtubules in Charcot-Marie-Tooth neuropathy

Mutations in the small heat shock protein HSPB1 (HSP27) are causative for Charcot-Marie-Tooth (CMT) neuropathy. We previously showed that a subset of these mutations displays higher chaperone activity and enhanced affinity to client proteins. We hypothesized that this excessive binding property might cause the HSPB1 mutant proteins to disturb the function of proteins essential for the maintenance or survival of peripheral neurons. In the present work, we explored this hypothesis further and compared the protein complexes formed by wild-type and mutant HSPB1. Tubulin came out as the most striking differential interacting protein, with hyperactive mutants binding more strongly to both tubulin and microtubules. This anomalous binding leads to a stabilization of the microtubule network in a microtubule-associated protein-like manner as reflected by resistance to cold depolymerization, faster network recovery after nocodazole treatment, and decreased rescue and catastrophe rates of individual microtubules. In a transgenic mouse model for mutant HSPB1 that recapitulates all features of CMT, we could confirm the enhanced interaction of mutant HSPB1 with tubulin. Increased stability of the microtubule network was also clear in neurons isolated from these mice. Since neuronal cells are particularly vulnerable to disturbances in microtubule dynamics, this mechanism might explain the neuron-specific CMT phenotype caused by HSPB1 mutations

Sensory-neuropathy-causing mutations in ATL3 cause aberrant ER membrane tethering

The endoplasmic reticulum (ER) is a complex network of sheets and tubules that is continuously remodeled. The relevance of this membrane dynamics is underscored by the fact that mutations in atlastins (ATLs), the ER fusion proteins in mammals, cause neurodegeneration. How defects in this process disrupt neuronal homeostasis is unclear. Using electron microscopy (EM) volume reconstruction of transfected cells, neurons, and patient fibroblasts, we show that hereditary sensory and autonomic neuropathy (HSAN)-causing ATL3 mutants promote aberrant ER tethering hallmarked by bundles of laterally attached ER tubules. In vitro, these mutants cause excessive liposome tethering, recapitulating the results in cells. Moreover, ATL3 variants retain their dimerization-dependent GTPase activity but are unable to promote membrane fusion, suggesting a defect in an intermediate step of the ATL3 functional cycle. Our data show that the effects of ATL3 mutations on ER network organization go beyond a loss of fusion and shed light on neuropathies caused by atlastin defects

Prospectus, September 28, 1973

OVERWHELMING RESPONSE TO ACTIVITIES WEEK; Four File Petitions For Senator; Variety Talent Needed For October Show; David Stanley Named To Head Parkland Prospectus Staff; Reactions To New Drinking Law; Toy For Kids And War; Guest Editorial; Prospectus In Perspective: Student President\u27s Report; Boycott Non-Union Lettuce; Roving Counselors New Addition To FSM Centers; Lake: \u27Energy...Essence of Art\u27; Walker Defends Positions On Schools, Lakes; Board Approves Operating Budget; New Faculty Members; Counselors\u27 Schedule For FSM; Prospectus Plan Presented To Board Members; Want To Sing, Swing, Play?; Students Find Voice In College Government; Candidates Draft Platforms, Elections On Oct. 10-11; Black Art/Poetry; Dental Services Free To Students; Audubon Society Opens Season; Monday\u27s Coach; Hustler Is Hustled As King Wins Crown; Outreach Program To Bridge Gap; \u27A Quarter\u27s Worth\u27 Selects Editor; Mailer To Lecture At River Forest; Mike Scruggs Wins Football Contest; Road Rally & Sports Car Club; Earle Grabs Successive Cross Country Titles; Linksmen Seventh In Golf Opener; Touch Football Gets Underway, Intramurals In Full Swing; Trucker\u27s Lead Bowling League; Fast Freddy\u27s Football Forecast; Carlin Social Parody Blows Mind; Mutt and Mortie; Board Discusses Student Rep; Dear Mr. Secretary; Explicit Needs Fulfilled By Black Groups; The Short Circuit; Letters From Our Readers; Debate Competition Opens Against Western Illinois; Classified Ads; Faculty Wives Outline Programs; Program List For 1973-74; LRC Ready For Students; Rosh Hashanah Signals Start Of Jewish Holidays; Callboard; I. E. Team Plans Intercollegiate Competition; Krannert Art Center Schedule; Staff Requests News Releaseshttps://spark.parkland.edu/prospectus_1973/1005/thumbnail.jp

The Grizzly, September 15, 1989

Greek Golden Age Growing Dark • U.C. Slasher Case Finally Closed • Letters: Physics Major Majorly Miffed; Wismer Eggs on Disgusted Diner • SAO Makes Room for Zimmer • Go Abroad: It\u27s Worth It • Mann\u27s Soda Can Hit with Crowd • Bears Upset Hoyas in Season Opener • Grizzlies Take Tourney with Defense • V-ball: Victors! • Endurance is Key • Athletes of the Week • Pledging: Git! • Myrin Booking • Lucas Heads Frosh Seminar • Dumas: Cook of Monte Cristo • Smith Donation • Freshmen Make Necessary Adjustmentshttps://digitalcommons.ursinus.edu/grizzlynews/1240/thumbnail.jp

Sensory neuropathy-causing mutations in ATL3 affect ER-mitochondria contact sites and impair axonal mitochondrial distribution

Axonopathies are neurodegenerative disorders caused by axonal degeneration, affecting predominantly the longest neurons. Several of these axonopathies are caused by genetic defects in proteins involved in the shaping and dynamics of the endoplasmic reticulum (ER); however, it is unclear how these defects impinge on neuronal survival. Given its central and widespread position within a cell, the ER is a pivotal player in inter-organelle communication. Here, we demonstrate that defects in the ER fusion protein ATL3, which were identified in patients suffering from hereditary sensory and autonomic neuropathy, result in an increased number of ER-mitochondria contact sites both in HeLa cells and in patient-derived fibroblasts. This increased contact is reflected in higher phospholipid metabolism, upregulated autophagy and augmented Ca2+ crosstalk between both organelles. Moreover, the mitochondria in these cells display lowered motility, and the number of axonal mitochondria in neurons expressing disease-causing mutations in ATL3 is strongly decreased. These results underscore the functional interdependence of subcellular organelles in health and disease and show that disorders caused by ER-shaping defects are more complex than previously assumed