Tubulin bond energies and microtubule biomechanics determined from nanoindentation in silico

Microtubules, the primary components of the chromosome segregation machinery, are stabilized by longitudinal and lateral non-covalent bonds between the tubulin subunits. However, the thermodynamics of these bonds and the microtubule physico-chemical properties are poorly understood. Here, we explore the biomechanics of microtubule polymers using multiscale computational modeling and nanoindentations in silico of a contiguous microtubule fragment. A close match between the simulated and experimental force-deformation spectra enabled us to correlate the microtubule biomechanics with dynamic structural transitions at the nanoscale. Our mechanical testing revealed that the compressed MT behaves as a system of rigid elements interconnected through a network of lateral and longitudinal elastic bonds. The initial regime of continuous elastic deformation of the microtubule is followed by the transition regime, during which the microtubule lattice undergoes discrete structural changes, which include first the reversible dissociation of lateral bonds followed by irreversible dissociation of the longitudinal bonds. We have determined the free energies of dissociation of the lateral (6.9+/-0.4 kcal/mol) and longitudinal (14.9+/-1.5 kcal/mol) tubulin-tubulin bonds. These values in conjunction with the large flexural rigidity of tubulin protofilaments obtained (18,000-26,000 pN*nm^2), support the idea that the disassembling microtubule is capable of generating a large mechanical force to move chromosomes during cell division. Our computational modeling offers a comprehensive quantitative platform to link molecular tubulin characteristics with the physiological behavior of microtubules. The developed in silico nanoindentation method provides a powerful tool for the exploration of biomechanical properties of other cytoskeletal and multiprotein assemblie

Variability in above- and belowground Carbon Stocks in a Siberian Larch Watershed

Permafrost soils store between 1330 and 1580Pg carbon (C), which is 3 times the amount of C in global vegetation, almost twice the amount of C in the atmosphere, and half of the global soil organic C pool. Despite the massive amount of C in permafrost, estimates of soil C storage in the high-latitude permafrost region are highly uncertain, primarily due to undersampling at all spatial scales; circumpolar soil C estimates lack sufficient continental spatial diversity, regional intensity, and replication at the field-site level. Siberian forests are particularly undersampled, yet the larch forests that dominate this region may store more than twice as much soil C as all other boreal forest types in the continuous permafrost zone combined. Here we present above- and belowground C stocks from 20 sites representing a gradient of stand age and structure in a larch watershed of the Kolyma River, near Chersky, Sakha Republic, Russia. We found that the majority of C stored in the top 1m of the watershed was stored belowground (92%), with 19% in the top 10cm of soil and 40% in the top 30cm. Carbon was more variable in surface soils (10cm; coefficient of variation (CV) = 0.35 between stands) than in the top 30cm (CV = 0.14) or soil profile to 1m (CV = 0.20). Combined active-layer and deep frozen deposits (surface – 15m) contained 205kgCm−2 (yedoma, non-ice wedge) and 331kgCm−2 (alas), which, even when accounting for landscape-level ice content, is an order of magnitude more C than that stored in the top meter of soil and 2 orders of magnitude more C than in aboveground biomass. Aboveground biomass was composed of primarily larch (53%) but also included understory vegetation (30%), woody debris (11%) and snag (6%) biomass. While aboveground biomass contained relatively little (8%) of the C stocks in the watershed, aboveground processes were linked to thaw depth and belowground C storage. Thaw depth was negatively related to stand age, and soil C density (top 10cm) was positively related to soil moisture and negatively related to moss and lichen cover. These results suggest that, as the climate warms, changes in stand age and structure may be as important as direct climate effects on belowground environmental conditions and permafrost C vulnerability

Факторы риска микробиологической неэффективности комплексной пробиотической терапии в отношении облигатной микрофлоры кишечника больных туберкулезом с множественной лекарственной устойчивостью возбудителя

The aim of the work was to identify risk factors for the absence of a microbiological effect when using complex probiotic therapy in patients with drug-resistant tuberculosis.Material and methods. The object of the study was 30 patients with tuberculosis in the course of anti-tuberculosis therapy, who received a course of complex probiotic therapy. The patients were divided into groups according to the microbiological effect of using the probiotic against Bifido and Lactobacterium spp .: Group 1 – restoration of Lactobacterium spp. Happened, 2 – did not happen, 1A – recovery of Bifidobacterium spp. Happened, 1B did not happen. With the help of statistical processing of the material, the main risk factors for reducing its effectiveness have been identified.Research results. Among all factors (gender, social status, HIV infection, immunodeficiency, smoking, alcohol dependence, clinical form of tuberculosis and anti-tuberculosis drugs taken), the risk of reducing the efficiency of the Lactobacterium spp. in tuberculosis patients it is shown in males (OR 2.500, p = 0.029) over the age of 50 (p = 0.008). However, a significant decrease in the effectiveness of complex probiotic therapy to restore the pool of Lactobacterium spp. in the intestinal biotope is statistically significant due to the male sex (OR 8,000, p = 0.013 and the number of CD4 + lymphocytes (p = 0.005).Conclusion. The main risk factors for a decrease in the rate of recovery of the pool of Lactobacterium spp. in patients with multidrug-resistant tuberculosis, the pathogen was male and female, and the recovery of the Bifidobacterium spp. depended on the male sex and the severity of immunodeficiency in the presence of HIV infection.Целью работы являлось выявление факторов риска отсутствия микробиологического эффекта при применении комплексной пробиотической терапии у пациентов с лекарственно резистентным туберкулезом.Материалы и методы. Объектом исследования явились 30 пациентов с туберкулезом в процессе противотуберкулезной терапии, получивших курс комплексной пробиотической терапии. Пациенты были разделены на группы согласно микробиологическому эффекту применения пробиотика в отношении Bifido- и Lactobacterium spp.: 1 группа – восстановление Lactobacterium spp. произошло, 2 – не произошло, 1А – восстановление Bifidobacterium spp. произошло, 1Б – не произошло. При помощи статистической обработки материала определены основные факторы риска снижения его эффективности.Результаты. Среди всех факторов (пол, социальный статус, ВИЧ-инфекция, иммунодефицит, курение, зависимость от алкоголя, клиническая форма туберкулеза и принимаемые противотуберкулезные препарты) риск снижения эффективности восстановления пула Lactobacterium spp. у больных туберкулезом показан у лиц мужского пола (ОШ 2,500, р=0,029) в возрасте старше 50 лет (р=0,008). Однако значительное снижение эффективности комплексной пробиотической терапии на восстановление пула Lactobacterium spp. в кишечном биотопе статистически значимо обусловлено мужским полом (ОШ 8,000, р=0,013 и количеством CD4+лимфоцитов (р=0,005).Заключение. Основными факторами риска снижения скорости восстановления пула Lactobacterium spp. у больных туберкулезом с множественной лекарственной устойчивостью возбудителя явились мужской пол и возраст, а восстановление пула Bifidobacterium spp. зависело от мужского пола и выраженности иммунодефицита при наличии ВИЧ-инфекции

The state of the Martian climate

60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes

Permafrost is warming at a global scale

Permafrost warming has the potential to amplify global climate change, because when frozen sediments thaw it unlocks soil organic carbon. Yet to date, no globally consistent assessment of permafrost temperature change has been compiled. Here we use a global data set of permafrost temperature time series from the Global Terrestrial Network for Permafrost to evaluate temperature change across permafrost regions for the period since the International Polar Year (2007-2009). During the reference decade between 2007 and 2016, ground temperature near the depth of zero annual amplitude in the continuous permafrost zone increased by 0.39 ± 0.15 °C. Over the same period, discontinuous permafrost warmed by 0.20 ± 0.10 °C. Permafrost in mountains warmed by 0.19 ± 0.05 °C and in Antarctica by 0.37 ± 0.10 °C. Globally, permafrost temperature increased by 0.29 ± 0.12 °C. The observed trend follows the Arctic amplification of air temperature increase in the Northern Hemisphere. In the discontinuous zone, however, ground warming occurred due to increased snow thickness while air temperature remained statistically unchanged

State of the climate in 2013

In 2013, the vast majority of the monitored climate variables reported here maintained trends established in recent decades. ENSO was in a neutral state during the entire year, remaining mostly on the cool side of neutral with modest impacts on regional weather patterns around the world. This follows several years dominated by the effects of either La Niña or El Niño events. According to several independent analyses, 2013 was again among the 10 warmest years on record at the global scale, both at the Earths surface and through the troposphere. Some regions in the Southern Hemisphere had record or near-record high temperatures for the year. Australia observed its hottest year on record, while Argentina and New Zealand reported their second and third hottest years, respectively. In Antarctica, Amundsen-Scott South Pole Station reported its highest annual temperature since records began in 1957. At the opposite pole, the Arctic observed its seventh warmest year since records began in the early 20th century. At 20-m depth, record high temperatures were measured at some permafrost stations on the North Slope of Alaska and in the Brooks Range. In the Northern Hemisphere extratropics, anomalous meridional atmospheric circulation occurred throughout much of the year, leading to marked regional extremes of both temperature and precipitation. Cold temperature anomalies during winter across Eurasia were followed by warm spring temperature anomalies, which were linked to a new record low Eurasian snow cover extent in May. Minimum sea ice extent in the Arctic was the sixth lowest since satellite observations began in 1979. Including 2013, all seven lowest extents on record have occurred in the past seven years. Antarctica, on the other hand, had above-average sea ice extent throughout 2013, with 116 days of new daily high extent records, including a new daily maximum sea ice area of 19.57 million km2 reached on 1 October. ENSO-neutral conditions in the eastern central Pacific Ocean and a negative Pacific decadal oscillation pattern in the North Pacific had the largest impacts on the global sea surface temperature in 2013. The North Pacific reached a historic high temperature in 2013 and on balance the globally-averaged sea surface temperature was among the 10 highest on record. Overall, the salt content in nearsurface ocean waters increased while in intermediate waters it decreased. Global mean sea level continued to rise during 2013, on pace with a trend of 3.2 mm yr-1 over the past two decades. A portion of this trend (0.5 mm yr-1) has been attributed to natural variability associated with the Pacific decadal oscillation as well as to ongoing contributions from the melting of glaciers and ice sheets and ocean warming. Global tropical cyclone frequency during 2013 was slightly above average with a total of 94 storms, although the North Atlantic Basin had its quietest hurricane season since 1994. In the Western North Pacific Basin, Super Typhoon Haiyan, the deadliest tropical cyclone of 2013, had 1-minute sustained winds estimated to be 170 kt (87.5 m s-1) on 7 November, the highest wind speed ever assigned to a tropical cyclone. High storm surge was also associated with Haiyan as it made landfall over the central Philippines, an area where sea level is currently at historic highs, increasing by 200 mm since 1970. In the atmosphere, carbon dioxide, methane, and nitrous oxide all continued to increase in 2013. As in previous years, each of these major greenhouse gases once again reached historic high concentrations. In the Arctic, carbon dioxide and methane increased at the same rate as the global increase. These increases are likely due to export from lower latitudes rather than a consequence of increases in Arctic sources, such as thawing permafrost. At Mauna Loa, Hawaii, for the first time since measurements began in 1958, the daily average mixing ratio of carbon dioxide exceeded 400 ppm on 9 May. The state of these variables, along with dozens of others, and the 2013 climate conditions of regions around the world are discussed in further detail in this 24th edition of the State of the Climate series. © 2014, American Meteorological Society. All rights reserved