Dynein structure and power stroke

Dynein ATPases are microtubule motors that are critical to diverse processes such as vesicle transport and the beating of sperm tails; however, their mechanism of force generation is unknown. Each dynein comprises a head, from which a stalk and a stem emerge. Here we use electron microscopy and image processing to reveal new structural details of dynein c, an isoform from Chlamydomonas reinhardtii flagella, at the start and end of its power stroke. Both stem and stalk are flexible, and the stem connects to the head by means of a linker approximately 10 nm long that we propose lies across the head. With both ADP and vanadate bound, the stem and stalk emerge from the head 10 nm apart. However, without nucleotide they emerge much closer together owing to a change in linker orientation, and the coiled-coil stalk becomes stiffer. The net result is a shortening of the molecule coupled to an approximately 15-nm displacement of the tip of the stalk. These changes indicate a mechanism for the dynein power stroke

Loss of ATRX in Chondrocytes Has Minimal Effects on Skeletal Development

BACKGROUND:Mutations in the human ATRX gene cause developmental defects, including skeletal deformities and dwarfism. ATRX encodes a chromatin remodeling protein, however the role of ATRX in skeletal development is currently unknown. METHODOLOGY/PRINCIPAL FINDINGS:We induced Atrx deletion in mouse cartilage using the Cre-loxP system, with Cre expression driven by the collagen II (Col2a1) promoter. Growth rate, body size and weight, and long bone length did not differ in Atrx(Col2cre) mice compared to control littermates. Histological analyses of the growth plate did not reveal any differences between control and mutant mice. Expression patterns of Sox9, a transcription factor required for cartilage morphogenesis, and p57, a marker of cell cycle arrest and hypertrophic chondrocyte differentiation, was unaffected. However, loss of ATRX in cartilage led to a delay in the ossification of the hips in some mice. We also observed hindlimb polydactily in one out of 61 mutants. CONCLUSIONS/SIGNIFICANCE:These findings indicate that ATRX is not directly required for development or growth of cartilage in the mouse, suggesting that the short stature in ATR-X patients is caused by defects in cartilage-extrinsic mechanisms

Biogeography of parasitic nematode communities in giant Galápagos tortoise: implications for conservation management

The Galápagos giant tortoise is an icon of the unique, endemic biodiversity of Galápagos, but little is known of its parasitic fauna. We assessed the diversity of parasitic nematode communities and their spatial distributions within four wild tortoise populations comprising three species across three Galápagos islands, and consider their implication for Galápagos tortoise conservation programmes. Coprological examinations revealed nematode eggs to be common, with more than 80% of tortoises infected within each wild population. Faecal samples from tortoises within captive breeding centres on Santa Cruz, Isabela and San Cristobal islands also were examined. Five different nematode egg types were identified: oxyuroid, ascarid, trichurid and two types of strongyle. Sequencing of the 18S small-subunit ribosomal RNA gene from adult nematodes passed with faeces identified novel sequences indicative of rhabditid and ascaridid species. In the wild, the composition of nematode communities varied according to tortoise species, which co-varied with island, but nematode diversity and abundance were reduced or altered in captive-reared animals. Evolutionary and ecological factors are likely responsible for the variation in nematode distributions in the wild. This possible species/island-parasite co-evolution has not been considered previously for Galápagos tortoises. We recommend that conservation efforts, such as the current Galápagos tortoise captive breeding/rearing and release programme, be managed with respect to parasite biogeography and host-parasite co-evolutionary processes in addition to the biogeography of the host

"They all work...when you stick to them" : a qualitative investigation of dieting, weight loss, and physical exercise, in obese individuals

BackgroundTo explore the extent to which people living with obesity have attempted to lose weight, their attitudes towards dieting, physical exercise and weight loss solutions, why their weight loss attempts have failed, and their opinions about what would be most beneficial to them in their struggle with their weight.MethodQualitative study, using open-ended interviews, of 76 people living with obesity in Victoria, Australia in 2006/7. Individuals with a BMI of 30 or over were recruited using articles in local newspapers, convenience sampling, and at a later stage purposive sampling techniques to diversify the sample. Data analysis was conducted by hand using a constant, comparative method to develop and test analytical categories. Data were interpreted both within team meetings and through providing research participants the chance to comment on the study findings.ResultsWhilst participants repeatedly turned to commercial diets in their weight loss attempts, few had used, or were motivated to participate in physical activity. Friends or family members had introduced most individuals to weight loss techniques. Those who took part in interventions with members of their social network were more likely to report feeling accepted and supported. Participants blamed themselves for being unable to maintain their weight loss or \u27stick\u27 to diets. Whilst diets did not result in sustained weight loss, two thirds of participants felt that dieting was an effective way to lose weight.ConclusionIndividuals with obesity receive numerous instructions about what to do to address their weight, but very few are given appropriate long term guidance or support with which to follow through those instructions. Understanding the positive role of social networks may be particularly important in engaging individuals in physical activity. Public health approaches to obesity must engage and consult with those currently living with obesity, if patterns of social change are to occur

Higher-order multipole amplitudes in charmonium radiative transitions

Using 24 million $\psi' \equiv \psi(2S)$ decays in CLEO-c, we have searched for higher multipole admixtures in electric-dipole-dominated radiative transitions in charmonia. We find good agreement between our data and theoretical predictions for magnetic quadrupole (M2) amplitudes in the transitions $\psi' \to \gamma \chi_{c1,2}$ and $\chi_{c1,2} \to \gamma J/\psi$, in striking contrast to some previous measurements. Let $b_2^J$ and $a_2^J$ denote the normalized M2 amplitudes in the respective aforementioned decays, where the superscript $J$ refers to the angular momentum of the $\chi_{cJ}$. By performing unbinned maximum likelihood fits to full five-parameter angular distributions, we determine the ratios $a_2^{J=1}/a_2^{J=2} = 0.67^{+0.19}_{-0.13}$ and $a_2^{J=1}/b_2^{J=1} = -2.27^{+0.57}_{-0.99}$, where the theoretical predictions are independent of the charmed quark magnetic moment and are $a_2^{J=1}/a_2^{J=2} = 0.676 \pm 0.071$ and $a_2^{J=1}/b_2^{J=1} = -2.27 \pm 0.16$.Comment: 32 pages, 7 figures, acceptance updat

The factor structure of the Forms of Self-Criticising/Attacking & Self-Reassuring Scale in thirteen distinct populations

There is considerable evidence that self-criticism plays a major role in the vulnerability to and recovery from psychopathology. Methods to measure this process, and its change over time, are therefore important for research in psychopathology and well-being. This study examined the factor structure of a widely used measure, the Forms of Self-Criticising/Attacking & Self-Reassuring Scale in thirteen nonclinical samples (N = 7510) from twelve different countries: Australia (N = 319), Canada (N = 383), Switzerland (N = 230), Israel (N = 476), Italy (N = 389), Japan (N = 264), the Netherlands (N = 360), Portugal (N = 764), Slovakia (N = 1326), Taiwan (N = 417), the United Kingdom 1 (N = 1570), the United Kingdom 2 (N = 883), and USA (N = 331). This study used more advanced analyses than prior reports: a bifactor item-response theory model, a two-tier item-response theory model, and a non-parametric item-response theory (Mokken) scale analysis. Although the original three-factor solution for the FSCRS (distinguishing between Inadequate-Self, Hated-Self, and Reassured-Self) had an acceptable fit, two-tier models, with two general factors (Self-criticism and Self-reassurance) demonstrated the best fit across all samples. This study provides preliminary evidence suggesting that this two-factor structure can be used in a range of nonclinical contexts across countries and cultures. Inadequate-Self and Hated-Self might not by distinct factors in nonclinical samples. Future work may benefit from distinguishing between self-correction versus shame-based self-criticism.Peer reviewe

Dalitz Plot Analysis of Ds to K+K-pi+

We perform a Dalitz plot analysis of the decay Ds to K+K-pi+ with the CLEO-c data set of 586/pb of e+e- collisions accumulated at sqrt(s) = 4.17 GeV. This corresponds to about 0.57 million D_s+D_s(*)- pairs from which we select 14400 candidates with a background of roughly 15%. In contrast to previous measurements we find good agreement with our data only by including an additional f_0(1370)pi+ contribution. We measure the magnitude, phase, and fit fraction of K*(892) K+, phi(1020)pi+, K0*(1430)K+, f_0(980)pi+, f_0(1710)pi+, and f_0(1370)pi+ contributions and limit the possible contributions of other KK and Kpi resonances that could appear in this decay.Comment: 21 Pages,available through http://www.lns.cornell.edu/public/CLNS/, submitted to PR

Search for D0 to p e- and D0 to pbar e+

Using data recorded by CLEO-c detector at CESR, we search for simultaneous baryon and lepton number violating decays of the D^0 meson, specifically, D^0 --> p-bar e^+, D^0-bar --> p-bar e^+, D^0 --> p e^- and D^0-bar --> p e^-. We set the following branching fraction upper limits: D^0 --> p-bar e^+ (D^0-bar --> p-bar e^+) p e^- (D^0-bar --> p e^-) < 1.2 * 10^{-5}, both at 90% confidence level.Comment: 10 pages, available through http://www.lns.cornell.edu/public/CLNS/, submitted to PRD. Comments: changed abstract, added reference for section 1, vertical axis in Fig.5 changed (starts from 1.5 rather than 2.0), fixed typo

Difference-based clustering of short time-course microarray data with replicates

<p>Abstract</p> <p>Background</p> <p>There are some limitations associated with conventional clustering methods for short time-course gene expression data. The current algorithms require prior domain knowledge and do not incorporate information from replicates. Moreover, the results are not always easy to interpret biologically.</p> <p>Results</p> <p>We propose a novel algorithm for identifying a subset of genes sharing a significant temporal expression pattern when replicates are used. Our algorithm requires no prior knowledge, instead relying on an observed statistic which is based on the first and second order differences between adjacent time-points. Here, a pattern is predefined as the sequence of symbols indicating direction and the rate of change between time-points, and each gene is assigned to a cluster whose members share a similar pattern. We evaluated the performance of our algorithm to those of K-means, Self-Organizing Map and the Short Time-series Expression Miner methods.</p> <p>Conclusions</p> <p>Assessments using simulated and real data show that our method outperformed aforementioned algorithms. Our approach is an appropriate solution for clustering short time-course microarray data with replicates.</p