Kinetochore-Independent Chromosome Poleward Movement during Anaphase of Meiosis II in Mouse Eggs

Kinetochores are considered to be the key structures that physically connect spindle microtubules to the chromosomes and play an important role in chromosome segregation during mitosis. Due to different mechanisms of spindle assembly between centrosome-containing mitotic cells and acentrosomal meiotic oocytes, it is unclear how a meiotic spindle generates the poleward forces to drive two rounds of meiotic chromosome segregation to achieve genome haploidization. We took advantage of the fact that DNA beads are able to induce bipolar spindle formation without kinetochores and studied the behavior of DNA beads in the induced spindle in mouse eggs during meiosis II. Interestingly, DNA beads underwent poleward movements that were similar in timing and speed to the meiotic chromosomes, although all the beads moved together to the same spindle pole. Disruption of dynein function abolished the poleward movements of DNA beads but not of the meiotic chromosomes, suggesting the existence of different dynein-dependent and dynein-independent force generation mechanisms for the chromosome poleward movement, and the latter may be dependent on the presence of kinetochores. Consistent with the observed DNA bead poleward movement, sperm haploid chromatin (which also induced bipolar spindle formation after injection to a metaphase egg without forming detectable kinetochore structures) also underwent similar poleward movement at anaphase as DNA beads. The results suggest that in the chromatin-induced meiotic spindles, kinetochore attachments to spindle microtubules are not absolutely required for chromatin poleward movements at anaphase

Factor structure and validity of the shoulder pain and disability index in a population-based study of people with shoulder symptoms

Background: The Shoulder Pain and Disability Index (SPADI) is a self-administered questionnaire that aims to measure pain and disability associated with shoulder disease. The aim of the present study was to investigate the construct validity and factor structure of the SPADI in a population-based study of patients with self-reported chronic shoulder symptoms. Methods: The North West Adelaide Health Study is a representative longitudinal cohort study of people aged 18 years and over. The original sample was randomly selected and recruited by telephone interview. Overall, 3 206 participants returned to the clinic during the second stage (2004-2006) and were asked to report whether they had pain, aching or stiffness on most days in either of their shoulders. Data was also collected on body mass index and shoulder range of motion (ROM) and demographic factors. The SPADI (numeric rating scale) was administered to participants with shoulder symptoms. Principal components factor analysis, with varimax rotation of factor loadings, was used to assess subscale structure of SPADI. Correlations between the SPADI, shoulder ROM and SF-36 were performed. Results: Overall, 22.3% of participants indicated that they had pain, aching or stiffness in either of their shoulders. SPADI results were available for 588 of participants with current shoulder symptoms. The internal consistency of the SPADI subscales were high (Cronbach's alpha > 0.92). Two factors, explaining 61.4% of the total variance were extracted by factor analysis. These were interpreted as disability and pain respectively. There was a strong negative correlation between SPADI disability subscale scores and shoulder range of motion. SPADI disability, but not pain, subscale scores were correlated with age. Conclusions: The SPADI is a valid measure to assess pain and disability in people with shoulder pain in a population-based study. In this setting, the SPADI had a bidimensional structure with both pain and disability subscales.Catherine L Hill, Susan Lester, Anne W Taylor, Michael E Shanahan, Tiffany K Gil

The Shoulder Pain and Disability Index demonstrates factor, construct and longitudinal validity

BACKGROUND: The Shoulder Pain and Disability Index (SPADI) is a self-report measure developed to evaluate patients with shoulder pathology. While some validation has been conducted, broader analyses are indicated. This study determined aspects of cross-sectional and longitudinal validity of the SPADI. METHODS: Community volunteers (n = 129) who self-identified as having shoulder pain were enrolled. Patients were examined by a physical therapist using a standardized assessment process to insure that their pain was musculoskeletal in nature. This included examination of pain reported during active and passive shoulder motion as reported on a visual analogue pain scale. Patients completed the SPADI, the Coping Strategies Questionnaire (CSQ) and the Sickness Impact Profile (SIP) at a baseline assessment and again 3 and 6 months later. Factor analysis with varimax rotation was used to assess subscale structure. Expectations regarding convergent and divergent subscales of CSQ and SIP were determined a priori and analysed using Pearson correlations. Constructed hypotheses that patients with a specific diagnosis or on pain medication would demonstrate higher SPADI scores were tested. Correlations between the observed changes recorded across different instruments were used to assess longitudinal validity. RESULTS: The internal consistencies of the SPADI subscales were high (α > 0.92). Factor analysis with varimax rotation indicated that the majority of items fell into 2 factors that represent pain and disability. Two difficult functional items tended to align with pain items. Higher pain and disability was correlated to passive or negative coping strategies, i.e., praying/hoping, catastrophizing on the CSQ. The correlations between subscales of the SPADI and SIP were low with divergent subscales and low to moderate with convergent subscales. Correlations, r > 0.60, were observed between the SPADI and pain reported on a VAS pain scale during active and passive movement. The two constructed validity hypotheses (on diagnosis and use of pain medications) were both supported (p < 0.01). The SPADI demonstrated significant changes over time, but these were poorly correlated to the SIP or CSQ suggesting that these scales measure different parameters. CONCLUSION: The SPADI is a valid measure to assess pain and disability in community-based patients reporting shoulder pain due to musculoskeletal pathology

Diabetes Health, Residence & Metabolism in Asians: the DHRMA study, research into foods from the Indian subcontinent - a blinded, randomised, placebo controlled trial

<p>Abstract</p> <p>Background</p> <p>Coronary heart disease (CHD) is highly prevalent amongst the South Asian communities in Britain. The reasons for this excess CHD risk are multifactorial, but in part relate to a susceptibility to diabetes mellitus - where the aberrant metabolism of non-esterified fatty acids (NEFA) and glucose are likely to underpin vascular disease in this population. Dietary intervention is an important and first line approach to manage increased CHD risk. However, there is limited information on the impact of the South Asian diet on CHD risk.</p> <p>Methods/Design</p> <p>The Diabetes Health, Residence & Metabolism in Asians (DHRMA) study is a blinded, randomised, placebo controlled trial that analyses the efficacy of reduced glycaemic index (GI) staples of the South Asian diet, in relation to cardio-metabolic risk factors that are commonly perturbed amongst South Asian populations - primarily glucose, fatty acid and lipoprotein metabolism and central adiposity. Using a 10-week dietary intervention study, 50 healthy South Asians will be randomised to receive either a DHRMA (reduced GI) supply of chapatti (bread), stone ground, high protein wheat flour and white basmati rice (high bran, unpolished) or commercially available (leading brand) versions chapatti wheat flour and basmati rice. Volunteers will be asked to complete a 75g oral glucose tolerance test at baseline and at 10-weeks follow-up, where blood metabolites and hormones, blood pressure and anthropometry will also be assessed in a standardised manner.</p> <p>Discussion</p> <p>It is anticipated that the information collected from this study help develop healthy diet options specific (but not exclusive) for South Asian ethnic communities.</p> <p>Trial registration</p> <p>Current Controlled Trials <a href="http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=ISRCTN02839188">ISRCTN02839188</a></p

Developmentally regulated GTP binding protein 1 (DRG1) controls microtubule dynamics

The mitotic spindle, essential for segregating the sister chromatids into the two evolving daughter cells, is composed of highly dynamic cytoskeletal filaments, the microtubules. The dynamics of microtubules are regulated by numerous microtubule associated proteins. We identify here Developmentally regulated GTP binding protein 1 (DRG1) as a microtubule binding protein with diverse microtubule-associated functions. In vitro, DRG1 can diffuse on microtubules, promote their polymerization, drive microtubule formation into bundles, and stabilize microtubules. HeLa cells with reduced DRG1 levels show delayed progression from prophase to anaphase because spindle formation is slowed down. To perform its microtubule-associated functions, DRG1, although being a GTPase, does not require GTP hydrolysis. However, all domains are required as truncated versions show none of the mentioned activities besides microtubule binding

Hydrodilatation, corticosteroids and adhesive capsulitis: A randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Hydrodilatation of the glenohumeral joint is by several authors reported to improve shoulder pain and range of motion for patients with adhesive capsulitis. Procedures described often involve the injection of corticosteroids, to which the reported treatment effects may be attributed. Any important contribution arising from the hydrodilatation procedure itself remains to be demonstrated.</p> <p>Methods</p> <p>In this randomized trial, a hydrodilatation procedure including corticosteroids was compared with the injection of corticosteroids without dilatation. Patients were given three injections with two-week intervals, and all injections were given under fluoroscopic guidance. Outcome measures were the Shoulder Pain and Disability Index (SPADI) and measures of active and passive range of motion. Seventy-six patients were included and groups were compared six weeks after treatment. The study was designed as an open trial.</p> <p>Results</p> <p>The groups showed a rather similar degree of improvement from baseline. According to a multiple regression analysis, the effect of dilatation was a mean improvement of 3 points (confidence interval: -5 to 11) on the SPADI 0–100 scale. T-tests did not demonstrate any significant between-group differences in range of motion.</p> <p>Conclusion</p> <p>This study did not identify any important treatment effects resulting from three hydrodilatations that included steroid compared with three steroid injections alone.</p> <p>Trial registration</p> <p>The study is registered in Current Controlled Trials with the registration number ISRCTN90567697.</p

Factor structure of the Shoulder Pain and Disability Index in patients with adhesive capsulitis

<p>Abstract</p> <p>Background</p> <p>The Shoulder Pain and Disability Index (SPADI) is a self-administered questionnaire that aims to measure pain and disability associated with shoulder disease. It consists of a pain section and a disability section with 13 items being responded to on visual analogue scales. Few researchers have investigated SPADI validity in specified diagnostic groups, although the selection of an evaluative instrument should be based on evidence of validity in the target patient group. The aim of the present study was to investigate factor structure of the SPADI in a study population of patients with adhesive capsulitis.</p> <p>Methods</p> <p>The questionnaire was administered to 191 patients with adhesive capsulitis. Descriptive statistics for items and a comparison of scores for the two subscales were produced. Internal consistency was analyzed by use of the Cronbach alpha and a principal components analysis with varimax rotation was conducted. Study design was cross-sectional.</p> <p>Results</p> <p>Two factors were extracted, but the factor structure failed to support the original division of items into separate pain and disability sections.</p> <p>Conclusion</p> <p>We found minimal evidence to justify the use of separate subscales for pain and disability. It is our impression that the SPADI should be viewed as essentially unidimensional in patients with adhesive capsulitis.</p

Kinetochore fiber formation in animal somatic cells : dueling mechanisms come to a draw

Author Posting. © The Author, 2005. This is the author's version of the work. It is posted here by permission of Springer for personal use, not for redistribution. The definitive version was published in Chromosoma 114 (2005): 310-318, doi:10.1007/s00412-005-0028-2.The attachment to and movement of a chromosome on the mitotic spindle is mediated by the formation of a bundle of microtubules (MTs) that tethers the kinetochore on the chromosome to a spindle pole. The origin of these “kinetochore fibers” (K-fibers) has been investigated for over 125 years. As noted in 1944 by Schrader, there are only three possible ways to form a K-fiber: either it a) grows from the pole until it contacts the kinetochore; b) grows directly from the kinetochore; or c) it forms as a result of an interaction between the pole and the chromosome. Since Schrader’s time it has been firmly established that K-fibers in centrosome-containing animal somatic cells form as kinetochores capture MTs growing from the spindle pole (route a). It is now similarly clear that in cells lacking centrosomes, including plants and many animal oocytes, K-fibers “self-assemble” from MTs generated by the chromosomes (route b). Can animal somatic cells form K-fibers in the absence of centrosomes by the “self-assembly” pathway? In 2000 the answer to this question was shown to be a resounding “yes”. With this result, the next question became whether the presence of a centrosome normally suppresses K-fiber self-assembly, or if this route works concurrently with centrosome-mediated K-fiber formation. This question, too, has recently been answered: observations on untreated live animal cells expressing GFP-tagged tubulin clearly show that kinetochores can nucleate the formation of their associated MTs in the presence of functional centrosomes. The concurrent operation of these two “dueling” routes for forming K-fibers in animals helps explain why the attachment of kinetochores and the maturation of K-fibers occur as quickly as it does on all chromosomes within a cell.The work is sponsored by NIH grant GMS 40198