Microtubules gate tau condensation to spatially regulate microtubule functions.

Tau is an abundant microtubule-associated protein in neurons. Tau aggregation into insoluble fibrils is a hallmark of Alzheimer's disease and other types of dementia1, yet the physiological state of tau molecules within cells remains unclear. Using single-molecule imaging, we directly observe that the microtubule lattice regulates reversible tau self-association, leading to localized, dynamic condensation of tau molecules on the microtubule surface. Tau condensates form selectively permissible barriers, spatially regulating the activity of microtubule-severing enzymes and the movement of molecular motors through their boundaries. We propose that reversible self-association of tau molecules, gated by the microtubule lattice, is an important mechanism of the biological functions of tau, and that oligomerization of tau is a common property shared between the physiological and disease-associated forms of the molecule

Teasing Apart Impacts of Human Activity and Regional Drought on Madagascar's Large Vertebrate Fauna: Insights From New Excavations at Tsimanampesotse and Antsirafaly

Madagascar experienced a major faunal turnover near the end of the first millenium CE that particularly affected terrestrial, large-bodied vertebrate species. Teasing apart the relative impacts of people and climate on this event requires a focus on regional records with good chronological control. These records may document coeval changes in rainfall, faunal composition, and human activities. Here we present new paleontological and paleoclimatological data from southwestern Madagascar, the driest part of the island today. We collected over 1500 subfossil bones from deposits at a coastal site called Antsirafaly and from both flooded and dry cave deposits at Tsimanampesotse National Park. We built a chronology of Late Holocene changes in faunal assemblages based on 65 radiocarbon-dated specimens and subfossil associations. We collected stalagmites primarily within Tsimanampesotse but also at two additional locations in southern Madagascar. These provided information regarding hydroclimate variability over the past 120,000 years. Prior research has supported a primary role for drought (rather than humans) in triggering faunal turnover at Tsimanampesotse. This is based on evidence of: (1) a large freshwater ecosystem west of what is now the hypersaline Lake Tsimanampesotse, which supported freshwater mollusks and waterfowl (including animals that could not survive on resources offered by the hypersaline lake today); (2) abundant now-extinct terrestrial vertebrates; (3) regional decline or disappearance of certain tree species; and (4) scant local human presence. Our new data allow us to document the hydroclimate of the subarid southwest during the Holocene, as well as shifts in faunal composition (including local extirpations, large-vertebrate population collapse, and the appearance of introduced species). These records affirm that climate alone cannot have produced the observed vertebrate turnover in the southwest. Human activity, including the introduction of cattle, as well as associated changes in habitat exploitation, also played an important role

Role of educational level in the relationship between Body Mass Index (BMI) and health-related quality of life (HRQL) among rural Spanish women

BACKGROUND: The impact of obesity on health-related quality of life (HRQL) has been little explored in rural areas. The goal of this study is to ascertain the association between obesity and HRQL among Spanish women living in a rural area, and the influence of their educational level. METHODS: Cross-sectional study with personal interview of 1298 women (aged 18 to 60) randomly selected from the electoral rolls of 14 towns in Galicia, a region in the north-west of Spain. HRQL was assessed using the SF-36 questionnaire. The association between body mass index (BMI) and suboptimal scores in the different HRQL dimensions was summarised using odds ratios (ORs), obtained from multivariate logistic regression models. Separate analyses were conducted for women who had finished their education younger than 16 years old and women with secondary education to assess differences in the relationship between BMI and HRQL according to educational level. RESULTS: Among women with primary or lower education, obesity was associated with a higher prevalence of suboptimal values in the following dimensions: Physical functioning (OR: 1.97; 95%CI: 1.22-3.18); Role-physical (OR: 1.81; 95%CI: 1.04-3.14); General health (OR: 1.76; 95%CI: 1.10-2.81); and Role-emotional (OR: 2.52; 95%CI: 1.27-5.03). In women with higher education, physical functioning was the only dimension associated with obesity (OR: 2.02: 95%CI 0.83-4.97). CONCLUSION: The impact of obesity on women's HRQL is greater among those with a lower educational level. This group registered higher prevalence of obesity and poorer self-perceived health.This study was funded by the Instituto de Salud Carlos III (grant 001/05).S

Unacylated ghrelin promotes adipogenesis in rodent bone marrow via ghrelin O-acyl transferase and GHS-R1a activity: evidence for target cell-induced acylation

Despite being unable to activate the cognate ghrelin receptor (GHS-R), unacylated ghrelin (UAG) possesses a unique activity spectrum that includes promoting bone marrow adipogenesis. Since a receptor mediating this action has not been identified, we re-appraised the potential interaction of UAG with GHS-R in the regulation of bone marrow adiposity. Surprisingly, the adipogenic effects of intra-bone marrow (ibm)-infused acylated ghrelin (AG) and UAG were abolished in male GHS-R-null mice. Gas chromatography showed that isolated tibial marrow adipocytes contain the medium-chain fatty acids utilised in the acylation of UAG, including octanoic acid. Additionally, immunohistochemistry and immunogold electron microscopy revealed that tibial marrow adipocytes show prominent expression of the UAG-activating enzyme ghrelin O-acyl transferase (GOAT), which is located in the membranes of lipid trafficking vesicles and in the plasma membrane. Finally, the adipogenic effect of ibm-infused UAG was completely abolished in GOAT-KO mice. Thus, the adipogenic action of exogenous UAG in tibial marrow is dependent upon acylation by GOAT and activation of GHS-R. This suggests that UAG is subject to target cell-mediated activation – a novel mechanism for manipulating hormone activity

Community-based prevention leads to an increase in condom use and a reduction in sexually transmitted infections (STIs) among men who have sex with men (MSM) and female sex workers (FSW): the Frontiers Prevention Project (FPP) evaluation results

<p>Abstract</p> <p>Background</p> <p>India has an estimated 2.0 million to 3.1 million people living with HIV; it has the highest number of HIV-positive people in Asia and ranks third in the world. The Frontiers Prevention Project (FPP) was implemented in 2002 to conduct targeted prevention intervention geared towards female sex workers (FSW) and men who have sex with men (MSM) in the state of Andhra Pradesh (AP). This paper reports the overall changes in behaviour and STI outcomes between 2003/4 and 2007 and also describes the changes attributed to the FPP.</p> <p>Methods</p> <p>The evaluation used two cross-sectional surveys among MSM and FSW at 24 sites in AP. Surveys were implemented using a similar methodology. Univariate analyses were conducted by comparing means: baseline vs. four-year follow-up and FPP vs. non-FPP. For both MSM and FSW, random and fixed-effects logit regression models at the site level were estimated for <it>condom use with last partner</it>, <it>syphilis sero-positivity </it>and <it>HSV 2 sero-positivity</it>. In addition, for FSW we estimated models for <it>condom use with regular partner</it>, and for MSM we estimated models for <it>condom use with last female partner</it>.</p> <p>Results</p> <p>Among MSM, fixed-effects analysis revealed that FPP was positively correlated with the probability of <it>condom use with last female sexual partner </it>and negatively correlated with the individual probability of <it>sero-positivity to syphilis and HSV 2</it>. Among FSW, the FPP intervention was significantly correlated with increased <it>condom use with regular partners </it>and with lower probability of <it>STI sero-positivity</it>.</p> <p>Discussion</p> <p>Important changes in behaviours related to an increase in prevention activities translated to reductions in STI sero-prevalence in AP, India. In contrast with non-FPP sites, the FPP sites experienced an intense community approach as part of the FPP intervention, and the general increase in condom use and its effect on STI sero-prevalence reflected the efficacy of these intense prevention activities focused on key populations in AP.</p

Search for New Physics in e mu X Data at D0 Using Sleuth: A Quasi-Model-Independent Search Strategy for New Physics

We present a quasi-model-independent search for the physics responsible for electroweak symmetry breaking. We define final states to be studied, and construct a rule that identifies a set of relevant variables for any particular final state. A new algorithm ("Sleuth") searches for regions of excess in those variables and quantifies the significance of any detected excess. After demonstrating the sensitivity of the method, we apply it to the semi-inclusive channel e mu X collected in 108 pb^-1 of ppbar collisions at sqrt(s) = 1.8 TeV at the D0 experiment during 1992-1996 at the Fermilab Tevatron. We find no evidence of new high p_T physics in this sample.Comment: 23 pages, 12 figures. Submitted to Physical Review

Real-time traffic event detection using Twitter data

Incident detection is an important component of intelligent transport systems and plays a key role in urban traffic management and provision of traveller information services. Due to its importance, a wide number of researchers have developed different algorithms for real-time incident detection. However, the main limitation of existing techniques is that they do not work well in conditions where random factors could influence traffic flows. Twitter is a valuable source of information as its users post events as they happen or shortly after. Therefore, Twitter data have been used to predict a wide variety of real-time outcomes. This paper aims to present a methodology for a real-time traffic event detection using Twitter. Tweets are obtained through the Twitter streaming application programming interface in real time with a geolocation filter. Then, the author used natural language processing techniques to process the tweets before they are fed into a text classification algorithm that identifies if it is traffic related or not. The authors implemented their methodology in the West Midlands region in the UK and obtained an overall accuracy of 92·86%

Ratio of the Isolated Photon Cross Sections at \sqrt{s} = 630 and 1800 GeV

The inclusive cross section for production of isolated photons has been measured in \pbarp collisions at $\sqrt{s} = 630$ GeV with the \D0 detector at the Fermilab Tevatron Collider. The photons span a transverse energy ($E_T$) range from 7-49 GeV and have pseudorapidity $|\eta| < 2.5$. This measurement is combined with to previous \D0 result at $\sqrt{s} = 1800$ GeV to form a ratio of the cross sections. Comparison of next-to-leading order QCD with the measured cross section at 630 GeV and ratio of cross sections show satisfactory agreement in most of the $E_T$ range.Comment: 7 pages. Published in Phys. Rev. Lett. 87, 251805, (2001

Intracellular directed evolution of proteins from combinatorial libraries based on conditional phage replication

Directed evolution is a powerful tool to improve the characteristics of biomolecules. Here we present a protocol for the intracellular evolution of proteins with distinct differences and advantages in comparison with established techniques. These include the ability to select for a particular function from a library of protein variants inside cells, minimizing undesired coevolution and propagation of nonfunctional library members, as well as allowing positive and negative selection logics using basally active promoters. A typical evolution experiment comprises the following stages: (i) preparation of a combinatorial M13 phagemid (PM) library expressing variants of the gene of interest (GOI) and preparation of the Escherichia coli host cells; (ii) multiple rounds of an intracellular selection process toward a desired activity; and (iii) the characterization of the evolved target proteins. The system has been developed for the selection of new orthogonal transcription factors (TFs) but is capable of evolving any gene—or gene circuit function—that can be linked to conditional M13 phage replication. Here we demonstrate our approach using as an example the directed evolution of the bacteriophage λ cI TF against two synthetic bidirectional promoters. The evolved TF variants enable simultaneous activation and repression against their engineered promoters and do not cross-react with the wild-type promoter, thus ensuring orthogonality. This protocol requires no special equipment, allowing synthetic biologists and general users to evolve improved biomolecules within ~7 weeks